New York University/Hospital for Joint Disease: Seminar in Advanced Rheumatology

NEW YORK – Handy mnemonic devices can help predict vaccine response in patients taking biologics for rheumatoid arthritis, according to Dr. Daniel E. Furst.

Vaccinating patients taking biologic agents for rheumatoid arthritis is tricky. The effects of both the vaccine and biologic can be T-cell dependent or independent, or sometimes both, and when the mechanisms match, the vaccine’s response will likely be attenuated, he said at a rheumatology meeting sponsored by New York University.

Think ‘PITH’ – (Human) Papillomavirus, Influenza A/B, Tetanus, and Hepatitis B – to remember which vaccines have protein-based antigens and are T-cell dependent, said Dr. Furst, a rheumatology professor at the University of California in Los Angeles.

For vaccines that have carbohydrate-based antigens, which are largely T-cell independent (B-cell dependent), remember ‘PHIM’: Pneumococcus, H. influenzae B, Influenza A/B, and Meningococcus.

Biologic agents that affect T-cells include methotrexate, the TNF inhibitors, abatacept, and tocilizumab. As a general rule, biologics that affect T-cells decrease one’s response to T-cell dependent vaccines. For example, etanercept has been shown to decrease by as much as half, as well as delay the response to, the hepatitis B vaccine in both normal controls and patients with RA.

In normal volunteers abatacept blunted the response to tetanus vaccine given 2 weeks later by about 50% and given 8 weeks later by about 20%, compared to normal controls (Arthritis Res. Ther. 2007;9:R38).

Likewise, tocilizumab has been shown to reduce the response to the influenza vaccine by about 15%, according to a study presented at EULAR 2007 in Barcelona.

B-cell dependent vaccine responses are diminished by B-cell directed therapy. For example, the SIERRA study of pneumococcal vaccination in rituximab-treated patients showed that, compared to methotrexate alone, a combination of rituximab plus methotrexate decreased the response to the vaccination at 4 weeks by 30% to 60% (Arthritis Rheum. 2010;62:64-74). "That’s just what we would expect," Dr. Furst noted.

It is important to note that biologics that affect T-cell independent mechanisms (B-cell directed therapy), such as rituximab, will not usually affect T-cell mediated vaccine responses. For example, rituximab does not change the response to tetanus toxoid, said Dr. Furst. Similarly, T-cell dependent biologics will not affect T-cell independent vaccinations, citing as an example the lack of effect of adalimumab on the response to the pneumococcal vaccine, according to a paper presented at EULAR in 2006.

The influenza A/B vaccine is an exception to the rule, because it first requires an early B-cell response followed by a T-cell response.

Dr. Furst recommends avoiding live attenuated virus vaccines in patients on biologics or immunosuppressive agents. Vaccines that are likely to be affected include those for varicella/zoster, intranasal influenza/H1N1, measles/mumps/rubella (MMR), yellow fever, oral polio, typhoid (Ty21a oral), vaccinia (smallpox), the BCG vaccine for tuberculosis, and rotavirus. Live viruses can result in disseminated disease in such patients, he said. Ideally patients should be immunized with these vaccines as needed before starting a biologic or any other immunosuppressive therapy.

Dr. Furst is the recipient of research funding/consultant/advisory board member of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor Ortho Biotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Handy mnemonic devices can help predict vaccine response in patients taking biologics for rheumatoid arthritis, according to Dr. Daniel E. Furst.

Vaccinating patients taking biologic agents for rheumatoid arthritis is tricky. The effects of both the vaccine and biologic can be T-cell dependent or independent, or sometimes both, and when the mechanisms match, the vaccine’s response will likely be attenuated, he said at a rheumatology meeting sponsored by New York University.

Think ‘PITH’ – (Human) Papillomavirus, Influenza A/B, Tetanus, and Hepatitis B – to remember which vaccines have protein-based antigens and are T-cell dependent, said Dr. Furst, a rheumatology professor at the University of California in Los Angeles.

For vaccines that have carbohydrate-based antigens, which are largely T-cell independent (B-cell dependent), remember ‘PHIM’: Pneumococcus, H. influenzae B, Influenza A/B, and Meningococcus.

Biologic agents that affect T-cells include methotrexate, the TNF inhibitors, abatacept, and tocilizumab. As a general rule, biologics that affect T-cells decrease one’s response to T-cell dependent vaccines. For example, etanercept has been shown to decrease by as much as half, as well as delay the response to, the hepatitis B vaccine in both normal controls and patients with RA.

In normal volunteers abatacept blunted the response to tetanus vaccine given 2 weeks later by about 50% and given 8 weeks later by about 20%, compared to normal controls (Arthritis Res. Ther. 2007;9:R38).

Likewise, tocilizumab has been shown to reduce the response to the influenza vaccine by about 15%, according to a study presented at EULAR 2007 in Barcelona.

B-cell dependent vaccine responses are diminished by B-cell directed therapy. For example, the SIERRA study of pneumococcal vaccination in rituximab-treated patients showed that, compared to methotrexate alone, a combination of rituximab plus methotrexate decreased the response to the vaccination at 4 weeks by 30% to 60% (Arthritis Rheum. 2010;62:64-74). "That’s just what we would expect," Dr. Furst noted.

It is important to note that biologics that affect T-cell independent mechanisms (B-cell directed therapy), such as rituximab, will not usually affect T-cell mediated vaccine responses. For example, rituximab does not change the response to tetanus toxoid, said Dr. Furst. Similarly, T-cell dependent biologics will not affect T-cell independent vaccinations, citing as an example the lack of effect of adalimumab on the response to the pneumococcal vaccine, according to a paper presented at EULAR in 2006.

The influenza A/B vaccine is an exception to the rule, because it first requires an early B-cell response followed by a T-cell response.

Dr. Furst recommends avoiding live attenuated virus vaccines in patients on biologics or immunosuppressive agents. Vaccines that are likely to be affected include those for varicella/zoster, intranasal influenza/H1N1, measles/mumps/rubella (MMR), yellow fever, oral polio, typhoid (Ty21a oral), vaccinia (smallpox), the BCG vaccine for tuberculosis, and rotavirus. Live viruses can result in disseminated disease in such patients, he said. Ideally patients should be immunized with these vaccines as needed before starting a biologic or any other immunosuppressive therapy.

Dr. Furst is the recipient of research funding/consultant/advisory board member of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor Ortho Biotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Handy mnemonic devices can help predict vaccine response in patients taking biologics for rheumatoid arthritis, according to Dr. Daniel E. Furst.

Vaccinating patients taking biologic agents for rheumatoid arthritis is tricky. The effects of both the vaccine and biologic can be T-cell dependent or independent, or sometimes both, and when the mechanisms match, the vaccine’s response will likely be attenuated, he said at a rheumatology meeting sponsored by New York University.

Think ‘PITH’ – (Human) Papillomavirus, Influenza A/B, Tetanus, and Hepatitis B – to remember which vaccines have protein-based antigens and are T-cell dependent, said Dr. Furst, a rheumatology professor at the University of California in Los Angeles.

For vaccines that have carbohydrate-based antigens, which are largely T-cell independent (B-cell dependent), remember ‘PHIM’: Pneumococcus, H. influenzae B, Influenza A/B, and Meningococcus.

Biologic agents that affect T-cells include methotrexate, the TNF inhibitors, abatacept, and tocilizumab. As a general rule, biologics that affect T-cells decrease one’s response to T-cell dependent vaccines. For example, etanercept has been shown to decrease by as much as half, as well as delay the response to, the hepatitis B vaccine in both normal controls and patients with RA.

In normal volunteers abatacept blunted the response to tetanus vaccine given 2 weeks later by about 50% and given 8 weeks later by about 20%, compared to normal controls (Arthritis Res. Ther. 2007;9:R38).

Likewise, tocilizumab has been shown to reduce the response to the influenza vaccine by about 15%, according to a study presented at EULAR 2007 in Barcelona.

B-cell dependent vaccine responses are diminished by B-cell directed therapy. For example, the SIERRA study of pneumococcal vaccination in rituximab-treated patients showed that, compared to methotrexate alone, a combination of rituximab plus methotrexate decreased the response to the vaccination at 4 weeks by 30% to 60% (Arthritis Rheum. 2010;62:64-74). "That’s just what we would expect," Dr. Furst noted.

It is important to note that biologics that affect T-cell independent mechanisms (B-cell directed therapy), such as rituximab, will not usually affect T-cell mediated vaccine responses. For example, rituximab does not change the response to tetanus toxoid, said Dr. Furst. Similarly, T-cell dependent biologics will not affect T-cell independent vaccinations, citing as an example the lack of effect of adalimumab on the response to the pneumococcal vaccine, according to a paper presented at EULAR in 2006.

The influenza A/B vaccine is an exception to the rule, because it first requires an early B-cell response followed by a T-cell response.

Dr. Furst recommends avoiding live attenuated virus vaccines in patients on biologics or immunosuppressive agents. Vaccines that are likely to be affected include those for varicella/zoster, intranasal influenza/H1N1, measles/mumps/rubella (MMR), yellow fever, oral polio, typhoid (Ty21a oral), vaccinia (smallpox), the BCG vaccine for tuberculosis, and rotavirus. Live viruses can result in disseminated disease in such patients, he said. Ideally patients should be immunized with these vaccines as needed before starting a biologic or any other immunosuppressive therapy.

Dr. Furst is the recipient of research funding/consultant/advisory board member of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor Ortho Biotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Musculoskeletal ultrasound is emerging as a technique for early detection of gout and rheumatoid arthritis, Dr. Jonathan Samuels said in a discussion that included a review of recent studies published by other researchers.

To its advantage, musculoskeletal ultrasound (US) is noninvasive, painless, and does not require exposure to radiation or contrast material. Dynamic assessment allows multiple joints to be viewed quickly during one sitting. Compared with MRI, musculoskeletal ultrasound is less costly, does not require the patient to lie still for prolonged periods, and is suitable for the claustrophobic patient, said Dr. Samuels, a rheumatologist at NYU Langone Medical Center, at a rheumatology meeting sponsored by New York University.

According to the American College of Rheumatology Musculoskeletal Ultrasound Task Force, "a future for US in American rheumatology seems certain. The improved clinical assessments and patient outcomes arising from the use of US should augment American rheumatology practice." (Arthritis Care Res. 2010;62:1206-19).

Yet, not many rheumatologists have incorporated musculoskeletal ultrasound into their practices. When Dr. Samuels surveyed the meeting attendees, roughly 50% indicated by a show of hands that they had taken a course in musculoskeletal ultrasound and 75% said it should become a standard clinical tool – but only 10% said they routinely used ultrasound.

One reason may be that learning opportunities are relatively sparse, and credentialing has not yet been standardized. While most European rheumatology fellowships include training in musculoskeletal ultrasound, such training is not standard or required in the United States. The UltraSound School of North American Rheumatologists (USSONAR) provides a suggested curriculum and on-line teaching and guidance, mostly for fellows and attendings interested in teaching ultrasound. It also offers an annual competency exam. The ACR began offering intensive, 2-day introductory training courses in 2010, providing the fundamentals of musculoskeletal US for rheumatologists who want to integrate ultrasound into their practices. New this year is a 3-day intermediate course for rheumatologists who have performed 60-100 scans within the past 2 years and have taken at least one beginner-level course.

The American Institute of Ultrasound in Medicine (AIUM) released Training Guidelines for the Performance of Musculoskeletal Ultrasound Examinations, but the ACR has not fully accepted the guidelines. There is currently no official certification process for musculoskeletal ultrasound, but that may be about to change. In February 2012, the ACR voted to develop and take ownership of a certification exam.

Dr. Samuels summarized two of the studies that suggest musculoskeletal ultrasound may allow early detection and treatment of subclinical rheumatoid arthritis and gout.

In a study from the Diakonhjemmet Hospital in Oslo (Norway) (Ann. Rheum. Dis. 2011;70:176-9), patients with baseline wrist synovitis as detected with ultrasound were twice as likely to develop erosions at 12 months, while the risk was only 28% for those with baseline MRI marrow edema.

Musculoskeletal ultrasound also was successfully used to detect monosodium urate deposits in gout patients and in patients with asymptomatic hyperuricemia in a nonrandomized prospective cohort study of 50 men. Early detection of uric acid deposits could permit early therapeutic intervention, possibly preventing future tophi and erosions.

For the study, 50 men aged 55-85 years were consecutively recruited during routine primary care visits to the Department of Veterans Affairs (Arthritis Care Res. 2011;63:1456-62). Exclusion criteria included current or prior history of inflammatory arthritis other than gout, asymptomatic chondrocalcinosis of the knee, total knee replacement, and history of severe knee trauma. Subjects were assessed for gout using ACR clinical criteria and serum uric acid levels measurement.

Subjects underwent musculoskeletal ultrasound of the knees and first metatarsophalangeal joints. Images were read by two blinded rheumatologists, who looked for such characteristic findings as the "double contour" sign (a hyperechoic band) over the femoral articular cartilage of the knees and tophi (heterogenous material often surrounded by a small anechoic rim).

Deposits were found in 7 of 14 gout patients, 5 of 17 with asymptomatic hyperuricemia. and 1 of 19 controls. Most of those with asymptomatic hyperuricemia and deposits met none of the ACR gout criteria. Even in those who met several of the gout criteria, there was no association between the number of ACR criteria met and level of deposits.

Serum uric acid measures did not differentiate subjects with asymptomatic hyperuricemia (mean of 8.0 mg/dL) from those with gout (mean of 8.1 mg/dL). The mean value in controls was 5.5 mg/dL.

The presence of deposits was associated with higher uric acid levels in the gout patients, at 9.4 mg/ dL for the seven patients with crystal deposits and 6.9 mg/ dL for the seven without deposits. Mean serum uric acid level did not differ in asymptomatic hyperuricemia subjects with and without deposits.

Within the 14 gout patients, less crystal deposition was seen in the subgroup of 8 patients on therapy. None of the asymptomatic hyperuricemia patients were being treated, but it would seem plausible that therapy would reduce the risk of deposits based on data observed in the gout group.

Dr. Samuels said he has no disclosures.

NEW YORK – Musculoskeletal ultrasound is emerging as a technique for early detection of gout and rheumatoid arthritis, Dr. Jonathan Samuels said in a discussion that included a review of recent studies published by other researchers.

To its advantage, musculoskeletal ultrasound (US) is noninvasive, painless, and does not require exposure to radiation or contrast material. Dynamic assessment allows multiple joints to be viewed quickly during one sitting. Compared with MRI, musculoskeletal ultrasound is less costly, does not require the patient to lie still for prolonged periods, and is suitable for the claustrophobic patient, said Dr. Samuels, a rheumatologist at NYU Langone Medical Center, at a rheumatology meeting sponsored by New York University.

According to the American College of Rheumatology Musculoskeletal Ultrasound Task Force, "a future for US in American rheumatology seems certain. The improved clinical assessments and patient outcomes arising from the use of US should augment American rheumatology practice." (Arthritis Care Res. 2010;62:1206-19).

Yet, not many rheumatologists have incorporated musculoskeletal ultrasound into their practices. When Dr. Samuels surveyed the meeting attendees, roughly 50% indicated by a show of hands that they had taken a course in musculoskeletal ultrasound and 75% said it should become a standard clinical tool – but only 10% said they routinely used ultrasound.

One reason may be that learning opportunities are relatively sparse, and credentialing has not yet been standardized. While most European rheumatology fellowships include training in musculoskeletal ultrasound, such training is not standard or required in the United States. The UltraSound School of North American Rheumatologists (USSONAR) provides a suggested curriculum and on-line teaching and guidance, mostly for fellows and attendings interested in teaching ultrasound. It also offers an annual competency exam. The ACR began offering intensive, 2-day introductory training courses in 2010, providing the fundamentals of musculoskeletal US for rheumatologists who want to integrate ultrasound into their practices. New this year is a 3-day intermediate course for rheumatologists who have performed 60-100 scans within the past 2 years and have taken at least one beginner-level course.

The American Institute of Ultrasound in Medicine (AIUM) released Training Guidelines for the Performance of Musculoskeletal Ultrasound Examinations, but the ACR has not fully accepted the guidelines. There is currently no official certification process for musculoskeletal ultrasound, but that may be about to change. In February 2012, the ACR voted to develop and take ownership of a certification exam.

Dr. Samuels summarized two of the studies that suggest musculoskeletal ultrasound may allow early detection and treatment of subclinical rheumatoid arthritis and gout.

In a study from the Diakonhjemmet Hospital in Oslo (Norway) (Ann. Rheum. Dis. 2011;70:176-9), patients with baseline wrist synovitis as detected with ultrasound were twice as likely to develop erosions at 12 months, while the risk was only 28% for those with baseline MRI marrow edema.

Musculoskeletal ultrasound also was successfully used to detect monosodium urate deposits in gout patients and in patients with asymptomatic hyperuricemia in a nonrandomized prospective cohort study of 50 men. Early detection of uric acid deposits could permit early therapeutic intervention, possibly preventing future tophi and erosions.

For the study, 50 men aged 55-85 years were consecutively recruited during routine primary care visits to the Department of Veterans Affairs (Arthritis Care Res. 2011;63:1456-62). Exclusion criteria included current or prior history of inflammatory arthritis other than gout, asymptomatic chondrocalcinosis of the knee, total knee replacement, and history of severe knee trauma. Subjects were assessed for gout using ACR clinical criteria and serum uric acid levels measurement.

Subjects underwent musculoskeletal ultrasound of the knees and first metatarsophalangeal joints. Images were read by two blinded rheumatologists, who looked for such characteristic findings as the "double contour" sign (a hyperechoic band) over the femoral articular cartilage of the knees and tophi (heterogenous material often surrounded by a small anechoic rim).

Deposits were found in 7 of 14 gout patients, 5 of 17 with asymptomatic hyperuricemia. and 1 of 19 controls. Most of those with asymptomatic hyperuricemia and deposits met none of the ACR gout criteria. Even in those who met several of the gout criteria, there was no association between the number of ACR criteria met and level of deposits.

Serum uric acid measures did not differentiate subjects with asymptomatic hyperuricemia (mean of 8.0 mg/dL) from those with gout (mean of 8.1 mg/dL). The mean value in controls was 5.5 mg/dL.

The presence of deposits was associated with higher uric acid levels in the gout patients, at 9.4 mg/ dL for the seven patients with crystal deposits and 6.9 mg/ dL for the seven without deposits. Mean serum uric acid level did not differ in asymptomatic hyperuricemia subjects with and without deposits.

Within the 14 gout patients, less crystal deposition was seen in the subgroup of 8 patients on therapy. None of the asymptomatic hyperuricemia patients were being treated, but it would seem plausible that therapy would reduce the risk of deposits based on data observed in the gout group.

Dr. Samuels said he has no disclosures.

NEW YORK – Musculoskeletal ultrasound is emerging as a technique for early detection of gout and rheumatoid arthritis, Dr. Jonathan Samuels said in a discussion that included a review of recent studies published by other researchers.

To its advantage, musculoskeletal ultrasound (US) is noninvasive, painless, and does not require exposure to radiation or contrast material. Dynamic assessment allows multiple joints to be viewed quickly during one sitting. Compared with MRI, musculoskeletal ultrasound is less costly, does not require the patient to lie still for prolonged periods, and is suitable for the claustrophobic patient, said Dr. Samuels, a rheumatologist at NYU Langone Medical Center, at a rheumatology meeting sponsored by New York University.

According to the American College of Rheumatology Musculoskeletal Ultrasound Task Force, "a future for US in American rheumatology seems certain. The improved clinical assessments and patient outcomes arising from the use of US should augment American rheumatology practice." (Arthritis Care Res. 2010;62:1206-19).

Yet, not many rheumatologists have incorporated musculoskeletal ultrasound into their practices. When Dr. Samuels surveyed the meeting attendees, roughly 50% indicated by a show of hands that they had taken a course in musculoskeletal ultrasound and 75% said it should become a standard clinical tool – but only 10% said they routinely used ultrasound.

One reason may be that learning opportunities are relatively sparse, and credentialing has not yet been standardized. While most European rheumatology fellowships include training in musculoskeletal ultrasound, such training is not standard or required in the United States. The UltraSound School of North American Rheumatologists (USSONAR) provides a suggested curriculum and on-line teaching and guidance, mostly for fellows and attendings interested in teaching ultrasound. It also offers an annual competency exam. The ACR began offering intensive, 2-day introductory training courses in 2010, providing the fundamentals of musculoskeletal US for rheumatologists who want to integrate ultrasound into their practices. New this year is a 3-day intermediate course for rheumatologists who have performed 60-100 scans within the past 2 years and have taken at least one beginner-level course.

The American Institute of Ultrasound in Medicine (AIUM) released Training Guidelines for the Performance of Musculoskeletal Ultrasound Examinations, but the ACR has not fully accepted the guidelines. There is currently no official certification process for musculoskeletal ultrasound, but that may be about to change. In February 2012, the ACR voted to develop and take ownership of a certification exam.

Dr. Samuels summarized two of the studies that suggest musculoskeletal ultrasound may allow early detection and treatment of subclinical rheumatoid arthritis and gout.

In a study from the Diakonhjemmet Hospital in Oslo (Norway) (Ann. Rheum. Dis. 2011;70:176-9), patients with baseline wrist synovitis as detected with ultrasound were twice as likely to develop erosions at 12 months, while the risk was only 28% for those with baseline MRI marrow edema.

Musculoskeletal ultrasound also was successfully used to detect monosodium urate deposits in gout patients and in patients with asymptomatic hyperuricemia in a nonrandomized prospective cohort study of 50 men. Early detection of uric acid deposits could permit early therapeutic intervention, possibly preventing future tophi and erosions.

For the study, 50 men aged 55-85 years were consecutively recruited during routine primary care visits to the Department of Veterans Affairs (Arthritis Care Res. 2011;63:1456-62). Exclusion criteria included current or prior history of inflammatory arthritis other than gout, asymptomatic chondrocalcinosis of the knee, total knee replacement, and history of severe knee trauma. Subjects were assessed for gout using ACR clinical criteria and serum uric acid levels measurement.

Subjects underwent musculoskeletal ultrasound of the knees and first metatarsophalangeal joints. Images were read by two blinded rheumatologists, who looked for such characteristic findings as the "double contour" sign (a hyperechoic band) over the femoral articular cartilage of the knees and tophi (heterogenous material often surrounded by a small anechoic rim).

Deposits were found in 7 of 14 gout patients, 5 of 17 with asymptomatic hyperuricemia. and 1 of 19 controls. Most of those with asymptomatic hyperuricemia and deposits met none of the ACR gout criteria. Even in those who met several of the gout criteria, there was no association between the number of ACR criteria met and level of deposits.

Serum uric acid measures did not differentiate subjects with asymptomatic hyperuricemia (mean of 8.0 mg/dL) from those with gout (mean of 8.1 mg/dL). The mean value in controls was 5.5 mg/dL.

The presence of deposits was associated with higher uric acid levels in the gout patients, at 9.4 mg/ dL for the seven patients with crystal deposits and 6.9 mg/ dL for the seven without deposits. Mean serum uric acid level did not differ in asymptomatic hyperuricemia subjects with and without deposits.

Within the 14 gout patients, less crystal deposition was seen in the subgroup of 8 patients on therapy. None of the asymptomatic hyperuricemia patients were being treated, but it would seem plausible that therapy would reduce the risk of deposits based on data observed in the gout group.

Dr. Samuels said he has no disclosures.

NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.

"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.

When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.

A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.

All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.

"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).

As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.

Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.

Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."

According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.

According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.

Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.

"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.

When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.

A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.

All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.

"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).

As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.

Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.

Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."

According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.

According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.

Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Abatacept may be helpful for treating rheumatoid arthritis in patients with concurrent hepatitis B, as long as patients are also given antiviral prophylaxis to prevent reactivation of their infection, according to the results of a small retrospective study presented at a rheumatology meeting sponsored by New York University.

"RA therapy in hepatitis B patients is complex. Flare of disease following immunosuppression is the primary concern. The major risk of hepatitis B comes not during but following immunosuppression, where reactivation can lead to severe, even fatal, hepatitis," said Dr. Daniel Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

In this study, 5 women and 3 men with RA were treated with abatacept and followed for a mean of 18 months. At baseline, all were positive for hepatitis B, as indicated by the presence of hepatitis B surface antigen (HBsAg), hepatitis B virus DNA greater than 20,000 IU/mL, or intermittently positive AST/ALT on liver biopsy. Six patients tested negative for hepatitis C. All patients had used disease-modifying antirheumatic drugs (DMARDs) previously, and 3 had previously used a biologic agent. At baseline, the mean DAS 28 (Disease Activity Score 28) was 5.

When abatacept treatment was initiated, four of the eight patients were already on antiviral therapy, with three patients on entecavir and one on tenofavir.

A statistically significant decrease in DAS 28 scores was seen in patients treated with abatacept plus an antiviral, compared with those not treated with the antiviral. The statistical differences developed slowly and became noticeable after 10-12 months of treatment; the response continued through the 18 months of follow-up. DAS 28 scores remained stable but did not improve in those treated with abatacept but not with an antiviral.

All four patients who did not receive antiviral prophylaxis had a reactivation of hepatitis B, as indicated by a more than 10-fold increase in hepatitis B virus DNA. In contrast, none of those who took antiviral medications had reactivation.

"There may be a place for abatacept when treating RA patients with hepatitis B. It must be used with background antiviral therapy and used continuously for a number of months. We are now doing a prospective, double-blind study," said Dr. Furst in discussing the recently published findings (Arthritis Care Res. 2012 March 5 [doi: 10.1002/acr.21654]).

As far as the use of other biologics, rituximab is probably contraindicated in patients with a history of hepatitis B, suggested Dr. Furst. Although there are not a lot of data to support this contraindication, the results of one study (J. Clin. Oncol. 2009;27:605-11) demonstrated reactivation of hepatitis B virus in 25% of lymphoma patients treated with rituximab plus cyclophosphamide, hydroxydoxorubicin, Oncovin (vincristine), and prednisone (CHOP), compared with no reactivation in those receiving CHOP alone, he said.

Dr. Furst said that he is reluctant to use tumor necrosis factor (TNF) inhibitors for RA patients with a history of hepatitis B. He said that he makes an exception in cases where hepatitis B is controlled, such as in patients who are negative for hepatitis B virus DNA.

Dr. Furst presented a literature review that identified 9 cases of hepatitis B reactivation in patients treated with TNF inhibitors, including 5 cases of severe illness. On the other hand, in a retrospective analysis of 67 HbsAg-positive patients, none of the patients experienced HBV activation. "I think the idea that TNF inhibitors will cause problems afterwards makes sense. I think they are tricky to use in patients with hepatitis B."

According to the World Health Organization, about 2 billion people worldwide have been infected with the hepatitis B virus, 350 million live with chronic infection, and 600,000 die each year due to the acute or chronic consequences of hepatitis B, such as liver cancer or cirrhosis. In Southeast Asia, 8%-10% of adults are chronically infected.

According to Dr. Furst, after exposure to the hepatitis B virus, 70% of people will develop acute hepatitis B but will remain asymptomatic. About 30% will have clinical symptoms, and 0.5%-1% will progress to fulminant hepatitis. Chronic infection occurs in 5%. "This means you probably have a good number of patients with some hepatitis B in their backgrounds. If you see many patients from Asia or South America, one really must screen for hepatitis B before starting the patient on biologics," he said.

Dr. Furst has received research funding from, been a consultant to, or served on the advisory boards of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor OrthoBiotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Smoking worsened the course of axial spondyloarthritis, leading to earlier onset of inflammatory back pain, more severe disease, more frequent inflammation and structural lesions of the sacroiliac joints and spine, and an increased risk of developing severe radiographic sacroiliitis, according to Dr. Christopher T. Ritchlin, who discussed the findings from two studies.

Unlike most other risk factors, smoking is modifiable, noted Dr. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.) Medical Center.

The studies involved patients who were in their 30s and early 40s. "These findings help us to focus on the risk factors we should be worried about in [spondyloarthritis (SpA)]," Dr. Ritchlin said at a rheumatology meeting sponsored by New York University.

At the 2011 American College of Rheumatology annual meeting, Dr. Pedro Machado of Leiden (the Netherlands) University Medical Center presented results from the DESIR (Devenir des Spondyloarthropathies Indifferenciées Récentes) cohort, a multicenter study in France (Ann. Rheum. Dis. 2011 Oct. 11 [doi:10.1136/annrheumdis-2011-200180]). This retrospective analysis looked at the records of 654 patients who met at least one set of international criteria for SpA. The patients were young (mean age, 33.6 years) and had back pain of relatively short duration (mean, 1.5 years). About one-third of the patients were classified as smokers, which was determined by physician interview. Information as to whether the patients were current smokers or how much they smoked was not provided. Multivariate analyses were adjusted for age, sex, duration of inflammatory back pain, race, and HLA-B27 status (Rheumatology News, June 2011, p. 38).

Smoking was found to be associated with a significantly earlier onset of back pain (P = .04) and higher disease activity, as measured on both the Ankylosing Spondylitis Disease Activity Index (P = .03) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = .003). Those who smoked also had worse functional status, as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) (P = .02). Quality of life was impaired for smokers, as measured by the Ankylosing Spondylitis Quality of Life Score (ASQol, P less than .001) and Short Form 36 physical and mental component scores (both P less than .001).

For the first time, smoking was determined to be associated with the presence of MRI inflammation and structural damage, according to Dr. Machado. MRI findings showed that those who smoked had more inflammation of the sacroiliac joints (odds ratio, 1.57; P = .02) and spine (OR, 2.33; P less than .001). Smoking was also associated with more extensive structural lesions of the sacroiliac joints (OR, 1.54; P = .03) and spine (OR, 2.02; P = .01) and a higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, P = .03), a measure of new bone formation.

"Taking into account that smoking is a potentially modifiable lifestyle factor, axial SpA patients who smoke should be strongly advised to quit this habit, as there seem to be disease-specific benefits that go beyond those described for the general population," Dr. Machado said.

Findings from the second study discussed by Dr. Ritchlin showed that smoking was also found to be a risk factor for severe radiographic sacroiliitis in patients with bilateral axial SpA in a cohort study of 151 patients meeting ASAS (Assessment of Spondyloarthritis International Society) criteria for axial SpA (Arthritis Rheum. 2011;63[suppl. 10]:512). Patients were divided into those who had mild disease (sacroilitis less than grade 4, n = 109) and those with more severe disease (sacroiliitis grade 4, n = 42). Most patients were in their late 30s or early 40s, and had the disease for 13 years or more. The study was presented at the 2011 American College of Rheumatology meeting by Grace Yoon of the University of California at San Francisco, where she is in the rheumatology division of the department of medicine.

In a multivariate logistic regression analysis, after adjustment for age and sex, smoking increased the risk of severe radiographic sacroiliitis (OR, 1.13, P = .006). The disease duration also increased the risk of severe radiographic sacroiliitis (OR, 1.07; P = .05) as did nonwhite ethnicity (OR, 3.3; P = .02), total hip arthroplasty (OR, 27.9; P = .0004), and a family history of ankylosing spondylitis (OR, 4.65; P = .01).

"What was really intriguing to me was the finding on MRI that there was an increase in inflammation seen in smokers," said Dr. Ritchlin. "The big question is, How does inflammation lead to osteoproliferation or new bone formation?" He suggested that both genetic factors and mechanobiologic factors such as axial myofascial tonicity influence the process.

Dr. Ritchlin reported financial relationships with Abbott, Amgen, Janssen, Pfizer, and UCB. Dr. Machado and Ms. Yoon reported that they had no relevant financial disclosures.

NEW YORK – Smoking worsened the course of axial spondyloarthritis, leading to earlier onset of inflammatory back pain, more severe disease, more frequent inflammation and structural lesions of the sacroiliac joints and spine, and an increased risk of developing severe radiographic sacroiliitis, according to Dr. Christopher T. Ritchlin, who discussed the findings from two studies.

Unlike most other risk factors, smoking is modifiable, noted Dr. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.) Medical Center.

The studies involved patients who were in their 30s and early 40s. "These findings help us to focus on the risk factors we should be worried about in [spondyloarthritis (SpA)]," Dr. Ritchlin said at a rheumatology meeting sponsored by New York University.

At the 2011 American College of Rheumatology annual meeting, Dr. Pedro Machado of Leiden (the Netherlands) University Medical Center presented results from the DESIR (Devenir des Spondyloarthropathies Indifferenciées Récentes) cohort, a multicenter study in France (Ann. Rheum. Dis. 2011 Oct. 11 [doi:10.1136/annrheumdis-2011-200180]). This retrospective analysis looked at the records of 654 patients who met at least one set of international criteria for SpA. The patients were young (mean age, 33.6 years) and had back pain of relatively short duration (mean, 1.5 years). About one-third of the patients were classified as smokers, which was determined by physician interview. Information as to whether the patients were current smokers or how much they smoked was not provided. Multivariate analyses were adjusted for age, sex, duration of inflammatory back pain, race, and HLA-B27 status (Rheumatology News, June 2011, p. 38).

Smoking was found to be associated with a significantly earlier onset of back pain (P = .04) and higher disease activity, as measured on both the Ankylosing Spondylitis Disease Activity Index (P = .03) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = .003). Those who smoked also had worse functional status, as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) (P = .02). Quality of life was impaired for smokers, as measured by the Ankylosing Spondylitis Quality of Life Score (ASQol, P less than .001) and Short Form 36 physical and mental component scores (both P less than .001).

For the first time, smoking was determined to be associated with the presence of MRI inflammation and structural damage, according to Dr. Machado. MRI findings showed that those who smoked had more inflammation of the sacroiliac joints (odds ratio, 1.57; P = .02) and spine (OR, 2.33; P less than .001). Smoking was also associated with more extensive structural lesions of the sacroiliac joints (OR, 1.54; P = .03) and spine (OR, 2.02; P = .01) and a higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, P = .03), a measure of new bone formation.

"Taking into account that smoking is a potentially modifiable lifestyle factor, axial SpA patients who smoke should be strongly advised to quit this habit, as there seem to be disease-specific benefits that go beyond those described for the general population," Dr. Machado said.

Findings from the second study discussed by Dr. Ritchlin showed that smoking was also found to be a risk factor for severe radiographic sacroiliitis in patients with bilateral axial SpA in a cohort study of 151 patients meeting ASAS (Assessment of Spondyloarthritis International Society) criteria for axial SpA (Arthritis Rheum. 2011;63[suppl. 10]:512). Patients were divided into those who had mild disease (sacroilitis less than grade 4, n = 109) and those with more severe disease (sacroiliitis grade 4, n = 42). Most patients were in their late 30s or early 40s, and had the disease for 13 years or more. The study was presented at the 2011 American College of Rheumatology meeting by Grace Yoon of the University of California at San Francisco, where she is in the rheumatology division of the department of medicine.

In a multivariate logistic regression analysis, after adjustment for age and sex, smoking increased the risk of severe radiographic sacroiliitis (OR, 1.13, P = .006). The disease duration also increased the risk of severe radiographic sacroiliitis (OR, 1.07; P = .05) as did nonwhite ethnicity (OR, 3.3; P = .02), total hip arthroplasty (OR, 27.9; P = .0004), and a family history of ankylosing spondylitis (OR, 4.65; P = .01).

"What was really intriguing to me was the finding on MRI that there was an increase in inflammation seen in smokers," said Dr. Ritchlin. "The big question is, How does inflammation lead to osteoproliferation or new bone formation?" He suggested that both genetic factors and mechanobiologic factors such as axial myofascial tonicity influence the process.

Dr. Ritchlin reported financial relationships with Abbott, Amgen, Janssen, Pfizer, and UCB. Dr. Machado and Ms. Yoon reported that they had no relevant financial disclosures.

NEW YORK – Smoking worsened the course of axial spondyloarthritis, leading to earlier onset of inflammatory back pain, more severe disease, more frequent inflammation and structural lesions of the sacroiliac joints and spine, and an increased risk of developing severe radiographic sacroiliitis, according to Dr. Christopher T. Ritchlin, who discussed the findings from two studies.

Unlike most other risk factors, smoking is modifiable, noted Dr. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.) Medical Center.

The studies involved patients who were in their 30s and early 40s. "These findings help us to focus on the risk factors we should be worried about in [spondyloarthritis (SpA)]," Dr. Ritchlin said at a rheumatology meeting sponsored by New York University.

At the 2011 American College of Rheumatology annual meeting, Dr. Pedro Machado of Leiden (the Netherlands) University Medical Center presented results from the DESIR (Devenir des Spondyloarthropathies Indifferenciées Récentes) cohort, a multicenter study in France (Ann. Rheum. Dis. 2011 Oct. 11 [doi:10.1136/annrheumdis-2011-200180]). This retrospective analysis looked at the records of 654 patients who met at least one set of international criteria for SpA. The patients were young (mean age, 33.6 years) and had back pain of relatively short duration (mean, 1.5 years). About one-third of the patients were classified as smokers, which was determined by physician interview. Information as to whether the patients were current smokers or how much they smoked was not provided. Multivariate analyses were adjusted for age, sex, duration of inflammatory back pain, race, and HLA-B27 status (Rheumatology News, June 2011, p. 38).

Smoking was found to be associated with a significantly earlier onset of back pain (P = .04) and higher disease activity, as measured on both the Ankylosing Spondylitis Disease Activity Index (P = .03) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P = .003). Those who smoked also had worse functional status, as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) (P = .02). Quality of life was impaired for smokers, as measured by the Ankylosing Spondylitis Quality of Life Score (ASQol, P less than .001) and Short Form 36 physical and mental component scores (both P less than .001).

For the first time, smoking was determined to be associated with the presence of MRI inflammation and structural damage, according to Dr. Machado. MRI findings showed that those who smoked had more inflammation of the sacroiliac joints (odds ratio, 1.57; P = .02) and spine (OR, 2.33; P less than .001). Smoking was also associated with more extensive structural lesions of the sacroiliac joints (OR, 1.54; P = .03) and spine (OR, 2.02; P = .01) and a higher modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, P = .03), a measure of new bone formation.

"Taking into account that smoking is a potentially modifiable lifestyle factor, axial SpA patients who smoke should be strongly advised to quit this habit, as there seem to be disease-specific benefits that go beyond those described for the general population," Dr. Machado said.

Findings from the second study discussed by Dr. Ritchlin showed that smoking was also found to be a risk factor for severe radiographic sacroiliitis in patients with bilateral axial SpA in a cohort study of 151 patients meeting ASAS (Assessment of Spondyloarthritis International Society) criteria for axial SpA (Arthritis Rheum. 2011;63[suppl. 10]:512). Patients were divided into those who had mild disease (sacroilitis less than grade 4, n = 109) and those with more severe disease (sacroiliitis grade 4, n = 42). Most patients were in their late 30s or early 40s, and had the disease for 13 years or more. The study was presented at the 2011 American College of Rheumatology meeting by Grace Yoon of the University of California at San Francisco, where she is in the rheumatology division of the department of medicine.

In a multivariate logistic regression analysis, after adjustment for age and sex, smoking increased the risk of severe radiographic sacroiliitis (OR, 1.13, P = .006). The disease duration also increased the risk of severe radiographic sacroiliitis (OR, 1.07; P = .05) as did nonwhite ethnicity (OR, 3.3; P = .02), total hip arthroplasty (OR, 27.9; P = .0004), and a family history of ankylosing spondylitis (OR, 4.65; P = .01).

"What was really intriguing to me was the finding on MRI that there was an increase in inflammation seen in smokers," said Dr. Ritchlin. "The big question is, How does inflammation lead to osteoproliferation or new bone formation?" He suggested that both genetic factors and mechanobiologic factors such as axial myofascial tonicity influence the process.

Dr. Ritchlin reported financial relationships with Abbott, Amgen, Janssen, Pfizer, and UCB. Dr. Machado and Ms. Yoon reported that they had no relevant financial disclosures.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – In a chart review of 264 patients who underwent bariatric surgery, near-complete resolution of osteoarthritis knee pain was reported by many patients.

Specifically, 71% of those who underwent roux-en-Y gastric bypass (RYGB) reported resolution of knee pain associated with osteoarthritis (OA), as did 63% of those who underwent laparoscopic sleeve gastrectomy (LSG) and 51% of those who underwent laparoscopic adjustable gastric banding (LAGB), according to coauthor Dr. Steven B. Abramson, who reported the findings at a rheumatology meeting sponsored by New York University.

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis," said Dr. Abramson, professor of medicine and pathology and senior vice president and vice dean for education, faculty, and academic affairs and director of the division of rheumatology at NYU Langone Medical Center.

The study was originally presented by James X. Lui, a medical student at New York University, at the 2011 World Congress of the Osteoarthritis Research Society International (OARSI) (Abst. 17).

Patients underwent bariatric surgery at Bellevue Hospital Center between January 2008 and March 2010. The average age was 42.5 years, 92% were female, and the average presurgical body mass index was 44.2 kg/m². Of the 264 patients, LAGB was performed in 192, RYGB in 53, and LSG in 19. OA was present in 88% of the patients, making it the most common obesity-related comorbidity.

At a mean 17.2 months’ follow-up, patients lost 28.4% of excess weight. Significant differences in weight loss was seen among the three types of surgeries (P less than .001), with those undergoing RYGB losing 43.6% of excess weight, compared with 37.4% in those undergoing LSG and 23.3% in those who underwent LAGB.

The investigators used the Assessment of Obesity-Related Comorbidities (AORC) to rate 10 comorbid conditions. For OA, the severity was rated as ranging from 0 (pain not present) to 5 (awaiting or has undergone joint replacement). There was no difference in preoperative AORC mean scores between surgical groups.

The three bariatric surgeries produced statistically significant resolution of all obesity-related comorbidities (P less than .001). Scores on the AORC decreased the most overall in patients who underwent RYGB (66%) versus 60% for LSG and 44% for LAGB, respectively.

Comparing postoperative to preoperative scores, OA improved following all three types of surgeries. The greatest change was seen in those who underwent RYGB (2 points), compared with those who underwent LSG (1.6 point change) or LAGB (1.2 point change).

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis."

The highest proportion of patients who had marked improvement of OA symptoms (postsurgical score of 0 on the AORC) was found in the RYGB group (71%), although good outcomes were also seen for 63% of the LSG and 51% of the LAGB groups.

Bariatric surgery lessened other comorbidities as well. For instance, resolution of hypertension was seen in 57% of the RYGB group, 29% of the LSG group, and 23% of the LAGB group. The effects on diabetes were less pronounced, with between 29% and 43% of patients reaching resolution, depending on the type of surgery.

Dr. Abramson suggests that the threshold for BMI as an indication for bariatric surgery could drop from BMI greater than 35 to BMI greater than 30 if there are comorbid conditions. "This includes a substantial percentage of U.S. patients with symptomatic knee OA who could become potential candidates for LAGB surgery if our preliminary studies were validated by prospective clinical trials," said Dr. Abramson.

Dr. Abramson also discussed the results of a study by Dr. Pascal Richette of the University of Paris who studied 140 obese patients with painful knee OA undergoing bariatric surgery (Ann. Rheum. Dis. 2011;70:139-44). As expected, a significant decrease in BMI resulted from surgery, as did a decrease in knee pain on the Western Ontario and McMaster Universities Osteoarthritis Index. Changes in levels of joint biomarkers, such as a significant increase of the N-terminal propeptide of type IIA collagen levels (a biomarker of cartilage synthesis) and a significant decrease in cartilage oligomeric protein (COMP) (a biomarker of cartilage degradation) suggests that structural effects on cartilage result from weight loss.

Dr. Abramson reported no relevant financial relationships.

NEW YORK – In a chart review of 264 patients who underwent bariatric surgery, near-complete resolution of osteoarthritis knee pain was reported by many patients.

Specifically, 71% of those who underwent roux-en-Y gastric bypass (RYGB) reported resolution of knee pain associated with osteoarthritis (OA), as did 63% of those who underwent laparoscopic sleeve gastrectomy (LSG) and 51% of those who underwent laparoscopic adjustable gastric banding (LAGB), according to coauthor Dr. Steven B. Abramson, who reported the findings at a rheumatology meeting sponsored by New York University.

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis," said Dr. Abramson, professor of medicine and pathology and senior vice president and vice dean for education, faculty, and academic affairs and director of the division of rheumatology at NYU Langone Medical Center.

The study was originally presented by James X. Lui, a medical student at New York University, at the 2011 World Congress of the Osteoarthritis Research Society International (OARSI) (Abst. 17).

Patients underwent bariatric surgery at Bellevue Hospital Center between January 2008 and March 2010. The average age was 42.5 years, 92% were female, and the average presurgical body mass index was 44.2 kg/m². Of the 264 patients, LAGB was performed in 192, RYGB in 53, and LSG in 19. OA was present in 88% of the patients, making it the most common obesity-related comorbidity.

At a mean 17.2 months’ follow-up, patients lost 28.4% of excess weight. Significant differences in weight loss was seen among the three types of surgeries (P less than .001), with those undergoing RYGB losing 43.6% of excess weight, compared with 37.4% in those undergoing LSG and 23.3% in those who underwent LAGB.

The investigators used the Assessment of Obesity-Related Comorbidities (AORC) to rate 10 comorbid conditions. For OA, the severity was rated as ranging from 0 (pain not present) to 5 (awaiting or has undergone joint replacement). There was no difference in preoperative AORC mean scores between surgical groups.

The three bariatric surgeries produced statistically significant resolution of all obesity-related comorbidities (P less than .001). Scores on the AORC decreased the most overall in patients who underwent RYGB (66%) versus 60% for LSG and 44% for LAGB, respectively.

Comparing postoperative to preoperative scores, OA improved following all three types of surgeries. The greatest change was seen in those who underwent RYGB (2 points), compared with those who underwent LSG (1.6 point change) or LAGB (1.2 point change).

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis."

The highest proportion of patients who had marked improvement of OA symptoms (postsurgical score of 0 on the AORC) was found in the RYGB group (71%), although good outcomes were also seen for 63% of the LSG and 51% of the LAGB groups.

Bariatric surgery lessened other comorbidities as well. For instance, resolution of hypertension was seen in 57% of the RYGB group, 29% of the LSG group, and 23% of the LAGB group. The effects on diabetes were less pronounced, with between 29% and 43% of patients reaching resolution, depending on the type of surgery.

Dr. Abramson suggests that the threshold for BMI as an indication for bariatric surgery could drop from BMI greater than 35 to BMI greater than 30 if there are comorbid conditions. "This includes a substantial percentage of U.S. patients with symptomatic knee OA who could become potential candidates for LAGB surgery if our preliminary studies were validated by prospective clinical trials," said Dr. Abramson.

Dr. Abramson also discussed the results of a study by Dr. Pascal Richette of the University of Paris who studied 140 obese patients with painful knee OA undergoing bariatric surgery (Ann. Rheum. Dis. 2011;70:139-44). As expected, a significant decrease in BMI resulted from surgery, as did a decrease in knee pain on the Western Ontario and McMaster Universities Osteoarthritis Index. Changes in levels of joint biomarkers, such as a significant increase of the N-terminal propeptide of type IIA collagen levels (a biomarker of cartilage synthesis) and a significant decrease in cartilage oligomeric protein (COMP) (a biomarker of cartilage degradation) suggests that structural effects on cartilage result from weight loss.

Dr. Abramson reported no relevant financial relationships.

NEW YORK – In a chart review of 264 patients who underwent bariatric surgery, near-complete resolution of osteoarthritis knee pain was reported by many patients.

Specifically, 71% of those who underwent roux-en-Y gastric bypass (RYGB) reported resolution of knee pain associated with osteoarthritis (OA), as did 63% of those who underwent laparoscopic sleeve gastrectomy (LSG) and 51% of those who underwent laparoscopic adjustable gastric banding (LAGB), according to coauthor Dr. Steven B. Abramson, who reported the findings at a rheumatology meeting sponsored by New York University.

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis," said Dr. Abramson, professor of medicine and pathology and senior vice president and vice dean for education, faculty, and academic affairs and director of the division of rheumatology at NYU Langone Medical Center.

The study was originally presented by James X. Lui, a medical student at New York University, at the 2011 World Congress of the Osteoarthritis Research Society International (OARSI) (Abst. 17).

Patients underwent bariatric surgery at Bellevue Hospital Center between January 2008 and March 2010. The average age was 42.5 years, 92% were female, and the average presurgical body mass index was 44.2 kg/m². Of the 264 patients, LAGB was performed in 192, RYGB in 53, and LSG in 19. OA was present in 88% of the patients, making it the most common obesity-related comorbidity.

At a mean 17.2 months’ follow-up, patients lost 28.4% of excess weight. Significant differences in weight loss was seen among the three types of surgeries (P less than .001), with those undergoing RYGB losing 43.6% of excess weight, compared with 37.4% in those undergoing LSG and 23.3% in those who underwent LAGB.

The investigators used the Assessment of Obesity-Related Comorbidities (AORC) to rate 10 comorbid conditions. For OA, the severity was rated as ranging from 0 (pain not present) to 5 (awaiting or has undergone joint replacement). There was no difference in preoperative AORC mean scores between surgical groups.

The three bariatric surgeries produced statistically significant resolution of all obesity-related comorbidities (P less than .001). Scores on the AORC decreased the most overall in patients who underwent RYGB (66%) versus 60% for LSG and 44% for LAGB, respectively.

Comparing postoperative to preoperative scores, OA improved following all three types of surgeries. The greatest change was seen in those who underwent RYGB (2 points), compared with those who underwent LSG (1.6 point change) or LAGB (1.2 point change).

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis."

The highest proportion of patients who had marked improvement of OA symptoms (postsurgical score of 0 on the AORC) was found in the RYGB group (71%), although good outcomes were also seen for 63% of the LSG and 51% of the LAGB groups.

Bariatric surgery lessened other comorbidities as well. For instance, resolution of hypertension was seen in 57% of the RYGB group, 29% of the LSG group, and 23% of the LAGB group. The effects on diabetes were less pronounced, with between 29% and 43% of patients reaching resolution, depending on the type of surgery.

Dr. Abramson suggests that the threshold for BMI as an indication for bariatric surgery could drop from BMI greater than 35 to BMI greater than 30 if there are comorbid conditions. "This includes a substantial percentage of U.S. patients with symptomatic knee OA who could become potential candidates for LAGB surgery if our preliminary studies were validated by prospective clinical trials," said Dr. Abramson.

Dr. Abramson also discussed the results of a study by Dr. Pascal Richette of the University of Paris who studied 140 obese patients with painful knee OA undergoing bariatric surgery (Ann. Rheum. Dis. 2011;70:139-44). As expected, a significant decrease in BMI resulted from surgery, as did a decrease in knee pain on the Western Ontario and McMaster Universities Osteoarthritis Index. Changes in levels of joint biomarkers, such as a significant increase of the N-terminal propeptide of type IIA collagen levels (a biomarker of cartilage synthesis) and a significant decrease in cartilage oligomeric protein (COMP) (a biomarker of cartilage degradation) suggests that structural effects on cartilage result from weight loss.

Dr. Abramson reported no relevant financial relationships.

NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.

These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.

Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."

PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.

In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.

Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).

No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.

Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.

Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.

NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.

These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.

Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."

PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.

In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.

Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).

No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.

Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.

Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.

NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.

These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.

Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."

PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.

In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.

Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).

No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.

Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.

Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.