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American College of Rheumatology (ACR): Annual Scientific Meeting
VIDEO: Biologics: Proposed guideline addresses perioperative management
WASHINGTON – Biologic agents should be stopped prior to elective total knee or hip arthroplasty in patients with rheumatic diseases, according to a draft guideline developed by the American College of Rheumatology and the American Association of Hip and Knee Surgeons.
The guideline, which address the perioperative management of antirheumatic medications in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, juvenile idiopathic arthritis (JIA), or lupus who are undergoing such surgery, is currently under review, Dr. Susan Goodman, MD, coprincipal investigator, reported at the annual meeting of the American College of Rheumatology.
The draft guideline was created because “guidance was needed for common clinical situations, even where data were sparse. We didn’t want to configure treatment mandates – that’s not what these are,” Dr. Goodman of Cornell University, New York, said.
The recommendations are conditional, she said, meaning that the benefits probably outweigh the harms, that the recommendations apply to most but not all patients, and that future research may lead to changes.
“They’re also preference sensitive,” she said, explaining that patients’ values and preferences should be carefully considered, as they might differ from those of the patient panel consulted during guideline development; the panel expressed greater concern about the risk of infection following surgery than about perioperative flares resulting from medication discontinuation.
Based on agreement by at least 80% of a voting panel which considered available evidence in the context of their clinical experience along with the input from the patient panel, the draft guideline states that:
• Current doses of methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine should be continued in patients with rheumatic diseases undergoing elective hip and knee replacement. This recommendation is based on an extensive literature review that showed the infection rate is decreased in patients who continue these medications, Dr. Goodman said.
• All biologics should be withheld prior to surgery in patients with inflammatory arthritis, and surgery should be planned for the end of the dosing cycle. This matter wasn’t specifically addressed in the literature; however, numerous randomized controlled trials outside of the surgical setting demonstrate an increased risk of infection associated with their use, she noted.
“All of the biologic medications were found to be associated with an increased risk of infection,” she said. “Because of this and the level of importance patients place on minimizing infection risk, we’ve recommended that biologics be withheld prior to surgery.”
• Tofacitinib, which was considered in a separate oral, targeted therapy category, should be withheld for at least 7 days prior to surgery in patients with RA, spondyloarthritis, and JIA. Data from systematic reviews and meta-analyses showed an increased risk of infection with tofacitinib, although more research is needed in order to “firm up” this recommendation, Dr. Goodman said.
• In lupus patients, rituximab and belimumab should be withheld prior to surgery, and surgery should be planned for the end of the dosing period.
“Again, this was not answered in the literature. We depended on observational studies that we reviewed that did show that patients with severe active lupus were at much higher risk for adverse events. But since rituximab isn’t approved by the [Food and Drug Administration] for use in lupus, and belimumab isn’t approved for use in severe lupus – and those seem to be the high-risk patients – we thought withholding them was more prudent,” she said.
• Patients with severe lupus should continue on current doses of methotrexate, mycophenolic acid, azathioprine, mizoribine, cyclosporine, and tacrolimus through surgery. This recommendation is based on indirect data from experience in organ transplant patients.
• All medications should be discontinued in patients whose lupus is not severe.
“Our recommendation is to withhold for 7 days to 2-5 days after surgery in the absence of any wound healing complications or any other complications,” she said, noting that the literature does not directly address this; the recommendation is based on indirect evidence in patients with either active infection or who are at risk for infection.
“We thought that careful monitoring of the patient would permit us to identify flare and intervene quickly. … and that, for mild cases of lupus, the morbidity associated with infection might not be greater than the morbidity associated with the disease flare,” she said.
• Biologics should be restarted once surgical wounds show evidence of healing and there is no clinical evidence of infection. The literature does not directly address this; the recommendation is based on the rationale for use of these medications in patients with either active infection or risk for infection.
• Current daily doses of glucocorticoids, rather than supraphysiologic doses, should be continued in adults with RA, lupus, or inflammatory arthritis. A meta-analysis and systematic review of randomized controlled trial data and observational data showed no hemodynamic difference between daily doses and stress doses.
“In addition, there are abundant observational data demonstrating an increase in infection in patients on chronic steroids greater than 15 mg, and we thought that part of the optimization of the patient would be getting them on the lowest possible steroid dose,” she said, stressing that this refers only to adults receiving glucocorticoids for their rheumatic disease, and not to those with a history of JIA who may have received steroids during development, or to those receiving glucocorticoids for primary, adrenal, or hypothalamic disease.
According to Dr. Goodman, the time is right for the introduction of these recommendations, because the increased use of disease-modifying drugs and biologics means that most patients coming in for these surgeries will be taking these medications.
Further, despite the widespread use of the medications, the rate of total knee and hip arthroplasty surgeries among patients with rheumatic diseases is about the same as it was 20 or 30 years ago – and their risk for devastating complications, including infections, remains high, she said, noting that appropriate medication management provides an opportunity to mitigate risk.
Coprincipal investigator, Bryan Springer, MD, further emphasized the importance of the guideline, noting that the 5-year survival among rheumatic disease patients who develop certain perioperative complications is lower than for many common cancers, and that the literature offers little guidance on managing medications in the perioperative period.
“We now have a document that’s based on the available evidence, and also based on expert opinion, to help us manage these patients much more thoroughly in the perioperative period,” Dr. Springer, an orthopedic surgeon in Charlotte, N.C., said during a press briefing on the guideline.
Dr. Springer highlighted the value of the unique collaboration between the ACR and the AAHKS, calling the effort a win both for patients, and for “collaborative efforts, collaborative research, which we just really don’t do enough of,” he said. “I hope this is a huge step towards that direction.”
This guideline development process was funded by the ACR and AAHKS.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Biologic agents should be stopped prior to elective total knee or hip arthroplasty in patients with rheumatic diseases, according to a draft guideline developed by the American College of Rheumatology and the American Association of Hip and Knee Surgeons.
The guideline, which address the perioperative management of antirheumatic medications in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, juvenile idiopathic arthritis (JIA), or lupus who are undergoing such surgery, is currently under review, Dr. Susan Goodman, MD, coprincipal investigator, reported at the annual meeting of the American College of Rheumatology.
The draft guideline was created because “guidance was needed for common clinical situations, even where data were sparse. We didn’t want to configure treatment mandates – that’s not what these are,” Dr. Goodman of Cornell University, New York, said.
The recommendations are conditional, she said, meaning that the benefits probably outweigh the harms, that the recommendations apply to most but not all patients, and that future research may lead to changes.
“They’re also preference sensitive,” she said, explaining that patients’ values and preferences should be carefully considered, as they might differ from those of the patient panel consulted during guideline development; the panel expressed greater concern about the risk of infection following surgery than about perioperative flares resulting from medication discontinuation.
Based on agreement by at least 80% of a voting panel which considered available evidence in the context of their clinical experience along with the input from the patient panel, the draft guideline states that:
• Current doses of methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine should be continued in patients with rheumatic diseases undergoing elective hip and knee replacement. This recommendation is based on an extensive literature review that showed the infection rate is decreased in patients who continue these medications, Dr. Goodman said.
• All biologics should be withheld prior to surgery in patients with inflammatory arthritis, and surgery should be planned for the end of the dosing cycle. This matter wasn’t specifically addressed in the literature; however, numerous randomized controlled trials outside of the surgical setting demonstrate an increased risk of infection associated with their use, she noted.
“All of the biologic medications were found to be associated with an increased risk of infection,” she said. “Because of this and the level of importance patients place on minimizing infection risk, we’ve recommended that biologics be withheld prior to surgery.”
• Tofacitinib, which was considered in a separate oral, targeted therapy category, should be withheld for at least 7 days prior to surgery in patients with RA, spondyloarthritis, and JIA. Data from systematic reviews and meta-analyses showed an increased risk of infection with tofacitinib, although more research is needed in order to “firm up” this recommendation, Dr. Goodman said.
• In lupus patients, rituximab and belimumab should be withheld prior to surgery, and surgery should be planned for the end of the dosing period.
“Again, this was not answered in the literature. We depended on observational studies that we reviewed that did show that patients with severe active lupus were at much higher risk for adverse events. But since rituximab isn’t approved by the [Food and Drug Administration] for use in lupus, and belimumab isn’t approved for use in severe lupus – and those seem to be the high-risk patients – we thought withholding them was more prudent,” she said.
• Patients with severe lupus should continue on current doses of methotrexate, mycophenolic acid, azathioprine, mizoribine, cyclosporine, and tacrolimus through surgery. This recommendation is based on indirect data from experience in organ transplant patients.
• All medications should be discontinued in patients whose lupus is not severe.
“Our recommendation is to withhold for 7 days to 2-5 days after surgery in the absence of any wound healing complications or any other complications,” she said, noting that the literature does not directly address this; the recommendation is based on indirect evidence in patients with either active infection or who are at risk for infection.
“We thought that careful monitoring of the patient would permit us to identify flare and intervene quickly. … and that, for mild cases of lupus, the morbidity associated with infection might not be greater than the morbidity associated with the disease flare,” she said.
• Biologics should be restarted once surgical wounds show evidence of healing and there is no clinical evidence of infection. The literature does not directly address this; the recommendation is based on the rationale for use of these medications in patients with either active infection or risk for infection.
• Current daily doses of glucocorticoids, rather than supraphysiologic doses, should be continued in adults with RA, lupus, or inflammatory arthritis. A meta-analysis and systematic review of randomized controlled trial data and observational data showed no hemodynamic difference between daily doses and stress doses.
“In addition, there are abundant observational data demonstrating an increase in infection in patients on chronic steroids greater than 15 mg, and we thought that part of the optimization of the patient would be getting them on the lowest possible steroid dose,” she said, stressing that this refers only to adults receiving glucocorticoids for their rheumatic disease, and not to those with a history of JIA who may have received steroids during development, or to those receiving glucocorticoids for primary, adrenal, or hypothalamic disease.
According to Dr. Goodman, the time is right for the introduction of these recommendations, because the increased use of disease-modifying drugs and biologics means that most patients coming in for these surgeries will be taking these medications.
Further, despite the widespread use of the medications, the rate of total knee and hip arthroplasty surgeries among patients with rheumatic diseases is about the same as it was 20 or 30 years ago – and their risk for devastating complications, including infections, remains high, she said, noting that appropriate medication management provides an opportunity to mitigate risk.
Coprincipal investigator, Bryan Springer, MD, further emphasized the importance of the guideline, noting that the 5-year survival among rheumatic disease patients who develop certain perioperative complications is lower than for many common cancers, and that the literature offers little guidance on managing medications in the perioperative period.
“We now have a document that’s based on the available evidence, and also based on expert opinion, to help us manage these patients much more thoroughly in the perioperative period,” Dr. Springer, an orthopedic surgeon in Charlotte, N.C., said during a press briefing on the guideline.
Dr. Springer highlighted the value of the unique collaboration between the ACR and the AAHKS, calling the effort a win both for patients, and for “collaborative efforts, collaborative research, which we just really don’t do enough of,” he said. “I hope this is a huge step towards that direction.”
This guideline development process was funded by the ACR and AAHKS.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Biologic agents should be stopped prior to elective total knee or hip arthroplasty in patients with rheumatic diseases, according to a draft guideline developed by the American College of Rheumatology and the American Association of Hip and Knee Surgeons.
The guideline, which address the perioperative management of antirheumatic medications in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, juvenile idiopathic arthritis (JIA), or lupus who are undergoing such surgery, is currently under review, Dr. Susan Goodman, MD, coprincipal investigator, reported at the annual meeting of the American College of Rheumatology.
The draft guideline was created because “guidance was needed for common clinical situations, even where data were sparse. We didn’t want to configure treatment mandates – that’s not what these are,” Dr. Goodman of Cornell University, New York, said.
The recommendations are conditional, she said, meaning that the benefits probably outweigh the harms, that the recommendations apply to most but not all patients, and that future research may lead to changes.
“They’re also preference sensitive,” she said, explaining that patients’ values and preferences should be carefully considered, as they might differ from those of the patient panel consulted during guideline development; the panel expressed greater concern about the risk of infection following surgery than about perioperative flares resulting from medication discontinuation.
Based on agreement by at least 80% of a voting panel which considered available evidence in the context of their clinical experience along with the input from the patient panel, the draft guideline states that:
• Current doses of methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine should be continued in patients with rheumatic diseases undergoing elective hip and knee replacement. This recommendation is based on an extensive literature review that showed the infection rate is decreased in patients who continue these medications, Dr. Goodman said.
• All biologics should be withheld prior to surgery in patients with inflammatory arthritis, and surgery should be planned for the end of the dosing cycle. This matter wasn’t specifically addressed in the literature; however, numerous randomized controlled trials outside of the surgical setting demonstrate an increased risk of infection associated with their use, she noted.
“All of the biologic medications were found to be associated with an increased risk of infection,” she said. “Because of this and the level of importance patients place on minimizing infection risk, we’ve recommended that biologics be withheld prior to surgery.”
• Tofacitinib, which was considered in a separate oral, targeted therapy category, should be withheld for at least 7 days prior to surgery in patients with RA, spondyloarthritis, and JIA. Data from systematic reviews and meta-analyses showed an increased risk of infection with tofacitinib, although more research is needed in order to “firm up” this recommendation, Dr. Goodman said.
• In lupus patients, rituximab and belimumab should be withheld prior to surgery, and surgery should be planned for the end of the dosing period.
“Again, this was not answered in the literature. We depended on observational studies that we reviewed that did show that patients with severe active lupus were at much higher risk for adverse events. But since rituximab isn’t approved by the [Food and Drug Administration] for use in lupus, and belimumab isn’t approved for use in severe lupus – and those seem to be the high-risk patients – we thought withholding them was more prudent,” she said.
• Patients with severe lupus should continue on current doses of methotrexate, mycophenolic acid, azathioprine, mizoribine, cyclosporine, and tacrolimus through surgery. This recommendation is based on indirect data from experience in organ transplant patients.
• All medications should be discontinued in patients whose lupus is not severe.
“Our recommendation is to withhold for 7 days to 2-5 days after surgery in the absence of any wound healing complications or any other complications,” she said, noting that the literature does not directly address this; the recommendation is based on indirect evidence in patients with either active infection or who are at risk for infection.
“We thought that careful monitoring of the patient would permit us to identify flare and intervene quickly. … and that, for mild cases of lupus, the morbidity associated with infection might not be greater than the morbidity associated with the disease flare,” she said.
• Biologics should be restarted once surgical wounds show evidence of healing and there is no clinical evidence of infection. The literature does not directly address this; the recommendation is based on the rationale for use of these medications in patients with either active infection or risk for infection.
• Current daily doses of glucocorticoids, rather than supraphysiologic doses, should be continued in adults with RA, lupus, or inflammatory arthritis. A meta-analysis and systematic review of randomized controlled trial data and observational data showed no hemodynamic difference between daily doses and stress doses.
“In addition, there are abundant observational data demonstrating an increase in infection in patients on chronic steroids greater than 15 mg, and we thought that part of the optimization of the patient would be getting them on the lowest possible steroid dose,” she said, stressing that this refers only to adults receiving glucocorticoids for their rheumatic disease, and not to those with a history of JIA who may have received steroids during development, or to those receiving glucocorticoids for primary, adrenal, or hypothalamic disease.
According to Dr. Goodman, the time is right for the introduction of these recommendations, because the increased use of disease-modifying drugs and biologics means that most patients coming in for these surgeries will be taking these medications.
Further, despite the widespread use of the medications, the rate of total knee and hip arthroplasty surgeries among patients with rheumatic diseases is about the same as it was 20 or 30 years ago – and their risk for devastating complications, including infections, remains high, she said, noting that appropriate medication management provides an opportunity to mitigate risk.
Coprincipal investigator, Bryan Springer, MD, further emphasized the importance of the guideline, noting that the 5-year survival among rheumatic disease patients who develop certain perioperative complications is lower than for many common cancers, and that the literature offers little guidance on managing medications in the perioperative period.
“We now have a document that’s based on the available evidence, and also based on expert opinion, to help us manage these patients much more thoroughly in the perioperative period,” Dr. Springer, an orthopedic surgeon in Charlotte, N.C., said during a press briefing on the guideline.
Dr. Springer highlighted the value of the unique collaboration between the ACR and the AAHKS, calling the effort a win both for patients, and for “collaborative efforts, collaborative research, which we just really don’t do enough of,” he said. “I hope this is a huge step towards that direction.”
This guideline development process was funded by the ACR and AAHKS.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ACR ANNUAL MEETING
Abatacept makes inroads in psoriatic arthritis
WASHINGTON – Abatacept achieved promising results in patients with psoriatic arthritis through 24 weeks of treatment in a placebo-controlled, phase III trial.
Based on these results of the trial, called ASTRAEA, the manufacturer of abatacept (Orencia) and sponsor of the study, Bristol-Myers Squibb, has submitted a Supplemental Biologics Application with the Food and Drug Administration as well as a Variation Application with the European Medicines Agency for an extended indication that includes the treatment of adult psoriatic arthritis (PsA).
ASTRAEA (Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Psoriatic Arthritis) enrolled 424 patients who met ACR PsA criteria and had evidence of active arthritis and psoriasis, plus inadequate response or intolerance to at least one nonbiologic disease-modifying antirheumatic drug (DMARD). The patients, of whom 60% failed prior tumor necrosis factor inhibitor (TNFi) treatment, were randomized to abatacept subcutaneous injection 125 mg/week or placebo. Median age was around 50 years, and about 50% were males. A total of 60% were on concomitant methotrexate.
“This was an active disease population, with about two-thirds having elevated C-reactive protein,” Dr. Mease noted at the annual meeting of the American College of Rheumatology.
A total of 39.4% of abatacept-treated patients achieved the primary endpoint of 24-week ACR20 response versus 22.3% of placebo patients (P less than .001). Improvement on ACR20 continued out to week 44.
Patients who were TNFi naive had better ACR20 responses than did those previously exposed to TNFi, he said. An ACR20 response occurred in 44% of TNFi-naive patients on abatacept, compared with 36.4% of TNFi-exposed patients. The same pattern was observed for ACR50 and ACR70 response rates.
A linear relationship was seen between response to abatacept and CRP baseline level, with a greater degree of response in those with elevated CRP.
Numerical trends favored abatacept for 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) responses, and X-ray assessment of structural damage. “We saw complete resolution of enthesitis and dactylitis at week 24 in 30%-40% of patients taking abatacept, and responses improved over time,” Dr. Mease told listeners. “Skin responses on the PASI 50 and PASI 75 were modest and not as good as we see with other agents,” Dr. Mease said.
Few serious adverse events were reported. There were three serious infections in the abatacept group and two in the placebo group at week 24.
“These data are consistent with phase II data. Overall, we saw beneficial trends with abatacept for all key endpoints, and the benefits were observed in both TNFi-exposed and TNFi-naive patients subgroups. Abatacept may be an appropriate option for PsA patients to try, especially those with musculoskeletal manifestations [given the modest responses in skin],” Dr. Mease said.
All of the ASTRAEA investigators had industry relationships, including some with Bristol-Myers Squibb. Two were employees of the company.
WASHINGTON – Abatacept achieved promising results in patients with psoriatic arthritis through 24 weeks of treatment in a placebo-controlled, phase III trial.
Based on these results of the trial, called ASTRAEA, the manufacturer of abatacept (Orencia) and sponsor of the study, Bristol-Myers Squibb, has submitted a Supplemental Biologics Application with the Food and Drug Administration as well as a Variation Application with the European Medicines Agency for an extended indication that includes the treatment of adult psoriatic arthritis (PsA).
ASTRAEA (Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Psoriatic Arthritis) enrolled 424 patients who met ACR PsA criteria and had evidence of active arthritis and psoriasis, plus inadequate response or intolerance to at least one nonbiologic disease-modifying antirheumatic drug (DMARD). The patients, of whom 60% failed prior tumor necrosis factor inhibitor (TNFi) treatment, were randomized to abatacept subcutaneous injection 125 mg/week or placebo. Median age was around 50 years, and about 50% were males. A total of 60% were on concomitant methotrexate.
“This was an active disease population, with about two-thirds having elevated C-reactive protein,” Dr. Mease noted at the annual meeting of the American College of Rheumatology.
A total of 39.4% of abatacept-treated patients achieved the primary endpoint of 24-week ACR20 response versus 22.3% of placebo patients (P less than .001). Improvement on ACR20 continued out to week 44.
Patients who were TNFi naive had better ACR20 responses than did those previously exposed to TNFi, he said. An ACR20 response occurred in 44% of TNFi-naive patients on abatacept, compared with 36.4% of TNFi-exposed patients. The same pattern was observed for ACR50 and ACR70 response rates.
A linear relationship was seen between response to abatacept and CRP baseline level, with a greater degree of response in those with elevated CRP.
Numerical trends favored abatacept for 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) responses, and X-ray assessment of structural damage. “We saw complete resolution of enthesitis and dactylitis at week 24 in 30%-40% of patients taking abatacept, and responses improved over time,” Dr. Mease told listeners. “Skin responses on the PASI 50 and PASI 75 were modest and not as good as we see with other agents,” Dr. Mease said.
Few serious adverse events were reported. There were three serious infections in the abatacept group and two in the placebo group at week 24.
“These data are consistent with phase II data. Overall, we saw beneficial trends with abatacept for all key endpoints, and the benefits were observed in both TNFi-exposed and TNFi-naive patients subgroups. Abatacept may be an appropriate option for PsA patients to try, especially those with musculoskeletal manifestations [given the modest responses in skin],” Dr. Mease said.
All of the ASTRAEA investigators had industry relationships, including some with Bristol-Myers Squibb. Two were employees of the company.
WASHINGTON – Abatacept achieved promising results in patients with psoriatic arthritis through 24 weeks of treatment in a placebo-controlled, phase III trial.
Based on these results of the trial, called ASTRAEA, the manufacturer of abatacept (Orencia) and sponsor of the study, Bristol-Myers Squibb, has submitted a Supplemental Biologics Application with the Food and Drug Administration as well as a Variation Application with the European Medicines Agency for an extended indication that includes the treatment of adult psoriatic arthritis (PsA).
ASTRAEA (Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Psoriatic Arthritis) enrolled 424 patients who met ACR PsA criteria and had evidence of active arthritis and psoriasis, plus inadequate response or intolerance to at least one nonbiologic disease-modifying antirheumatic drug (DMARD). The patients, of whom 60% failed prior tumor necrosis factor inhibitor (TNFi) treatment, were randomized to abatacept subcutaneous injection 125 mg/week or placebo. Median age was around 50 years, and about 50% were males. A total of 60% were on concomitant methotrexate.
“This was an active disease population, with about two-thirds having elevated C-reactive protein,” Dr. Mease noted at the annual meeting of the American College of Rheumatology.
A total of 39.4% of abatacept-treated patients achieved the primary endpoint of 24-week ACR20 response versus 22.3% of placebo patients (P less than .001). Improvement on ACR20 continued out to week 44.
Patients who were TNFi naive had better ACR20 responses than did those previously exposed to TNFi, he said. An ACR20 response occurred in 44% of TNFi-naive patients on abatacept, compared with 36.4% of TNFi-exposed patients. The same pattern was observed for ACR50 and ACR70 response rates.
A linear relationship was seen between response to abatacept and CRP baseline level, with a greater degree of response in those with elevated CRP.
Numerical trends favored abatacept for 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) responses, and X-ray assessment of structural damage. “We saw complete resolution of enthesitis and dactylitis at week 24 in 30%-40% of patients taking abatacept, and responses improved over time,” Dr. Mease told listeners. “Skin responses on the PASI 50 and PASI 75 were modest and not as good as we see with other agents,” Dr. Mease said.
Few serious adverse events were reported. There were three serious infections in the abatacept group and two in the placebo group at week 24.
“These data are consistent with phase II data. Overall, we saw beneficial trends with abatacept for all key endpoints, and the benefits were observed in both TNFi-exposed and TNFi-naive patients subgroups. Abatacept may be an appropriate option for PsA patients to try, especially those with musculoskeletal manifestations [given the modest responses in skin],” Dr. Mease said.
All of the ASTRAEA investigators had industry relationships, including some with Bristol-Myers Squibb. Two were employees of the company.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Week 24 ACR20 response rates were 39.4% for abatacept vs. 22.3% for placebo (P less than .001).
Data source: International, randomized, double-blind, multicenter phase III study of 424 patients with active psoriatic arthritis.
Disclosures: Bristol-Myers Squibb funded the study. All of the investigators had industry relationships, including some with Bristol-Myers Squibb. Two were employees of the company.
Continue DMARDs, biologics in RA surgery patients
WASHINGTON – The perioperative use of disease-modifying antirheumatic drug monotherapy or combined therapy with methotrexate and a tumor necrosis factor (TNF) inhibitor is not associated with increased rates of postoperative infectious complications or wound infections in patients with rheumatoid arthritis, according to findings from a retrospective review of more than 9,000 surgeries.
With respect to monotherapy, treatment was continued in 1,951 of 2,601 surgeries among patients receiving methotrexate, in 1,496 of 2,012 surgeries among patients receiving hydroxychloroquine, and in 508 of 652 surgeries among patient receiving leflunomide. The odds ratios for postoperative infection (including urinary tract, pneumonia, or sepsis) and postoperative wound infection, respectively, were 0.79 and 0.77 with methotrexate continuation, 0.93 and 0.86 with hydroxychloroquine continuation, and 0.78 and 0.87 with leflunomide continuation, Hsin-Hsuan Juo, MD, reported at the annual meeting of the American College of Rheumatology.
Data for this study were derived from the U.S. Department of Veterans Affairs administrative database and surgical quality registry. Rheumatoid arthritis patients who underwent a surgical procedure and who were on at least one disease-modifying antirheumatic drug (DMARD) or one biologic agent in the perioperative period during the study period of Oct. 1, 1999, through Sept. 30, 2009, were included. Subjects had a mean age of 67 years, and 91% were men.
The finding that the continuation of DMARD monotherapy or the combination of methotrexate and TNF inhibitor therapy for RA in the perioperative setting was not associated with increased rates of overall postoperative infectious complications and wound infections is important, because many patients are advised to stop taking these drugs prior to surgery because of concerns about increased susceptibility to infection. Discontinuing RA medication can increase the risk of disease flares requiring treatment with prednisone, which can further increase the risk of postsurgical complications, Dr. Juo said.
Clear, consistent guidance on the continuation of treatment among RA patients undergoing surgery has been lacking, she said, noting that guidelines over the years from the ACR, the British Society for Rheumatology, and the Canadian Rheumatology Association have differed in their recommendations.
A new draft guideline reported the morning of Dr. Juo’s presentation at the ACR annual meeting recommended continuing DMARDs but discontinuing biologics prior to surgery, but that guideline is limited to orthopedic surgery among patients with various rheumatic diseases.
“With literature review, the results are conflicting as well; some recommend continuing medication, and others recommend discontinuing medications prior to surgery,” she said.
The current findings, though limited by the study’s observational design and generally older, male population, suggest that continuing antirheumatic medications during the perioperative period is not associated with increased rates of postoperative complications.
“Our study results suggest that discontinuing DMARDs and biologic agents prior to surgery may not be necessary. Therefore, being on DMARDs or biologic agents should not preclude patients from receiving urgent surgeries,” Dr. Juo concluded.
Dr. Juo reported having no disclosures.
WASHINGTON – The perioperative use of disease-modifying antirheumatic drug monotherapy or combined therapy with methotrexate and a tumor necrosis factor (TNF) inhibitor is not associated with increased rates of postoperative infectious complications or wound infections in patients with rheumatoid arthritis, according to findings from a retrospective review of more than 9,000 surgeries.
With respect to monotherapy, treatment was continued in 1,951 of 2,601 surgeries among patients receiving methotrexate, in 1,496 of 2,012 surgeries among patients receiving hydroxychloroquine, and in 508 of 652 surgeries among patient receiving leflunomide. The odds ratios for postoperative infection (including urinary tract, pneumonia, or sepsis) and postoperative wound infection, respectively, were 0.79 and 0.77 with methotrexate continuation, 0.93 and 0.86 with hydroxychloroquine continuation, and 0.78 and 0.87 with leflunomide continuation, Hsin-Hsuan Juo, MD, reported at the annual meeting of the American College of Rheumatology.
Data for this study were derived from the U.S. Department of Veterans Affairs administrative database and surgical quality registry. Rheumatoid arthritis patients who underwent a surgical procedure and who were on at least one disease-modifying antirheumatic drug (DMARD) or one biologic agent in the perioperative period during the study period of Oct. 1, 1999, through Sept. 30, 2009, were included. Subjects had a mean age of 67 years, and 91% were men.
The finding that the continuation of DMARD monotherapy or the combination of methotrexate and TNF inhibitor therapy for RA in the perioperative setting was not associated with increased rates of overall postoperative infectious complications and wound infections is important, because many patients are advised to stop taking these drugs prior to surgery because of concerns about increased susceptibility to infection. Discontinuing RA medication can increase the risk of disease flares requiring treatment with prednisone, which can further increase the risk of postsurgical complications, Dr. Juo said.
Clear, consistent guidance on the continuation of treatment among RA patients undergoing surgery has been lacking, she said, noting that guidelines over the years from the ACR, the British Society for Rheumatology, and the Canadian Rheumatology Association have differed in their recommendations.
A new draft guideline reported the morning of Dr. Juo’s presentation at the ACR annual meeting recommended continuing DMARDs but discontinuing biologics prior to surgery, but that guideline is limited to orthopedic surgery among patients with various rheumatic diseases.
“With literature review, the results are conflicting as well; some recommend continuing medication, and others recommend discontinuing medications prior to surgery,” she said.
The current findings, though limited by the study’s observational design and generally older, male population, suggest that continuing antirheumatic medications during the perioperative period is not associated with increased rates of postoperative complications.
“Our study results suggest that discontinuing DMARDs and biologic agents prior to surgery may not be necessary. Therefore, being on DMARDs or biologic agents should not preclude patients from receiving urgent surgeries,” Dr. Juo concluded.
Dr. Juo reported having no disclosures.
WASHINGTON – The perioperative use of disease-modifying antirheumatic drug monotherapy or combined therapy with methotrexate and a tumor necrosis factor (TNF) inhibitor is not associated with increased rates of postoperative infectious complications or wound infections in patients with rheumatoid arthritis, according to findings from a retrospective review of more than 9,000 surgeries.
With respect to monotherapy, treatment was continued in 1,951 of 2,601 surgeries among patients receiving methotrexate, in 1,496 of 2,012 surgeries among patients receiving hydroxychloroquine, and in 508 of 652 surgeries among patient receiving leflunomide. The odds ratios for postoperative infection (including urinary tract, pneumonia, or sepsis) and postoperative wound infection, respectively, were 0.79 and 0.77 with methotrexate continuation, 0.93 and 0.86 with hydroxychloroquine continuation, and 0.78 and 0.87 with leflunomide continuation, Hsin-Hsuan Juo, MD, reported at the annual meeting of the American College of Rheumatology.
Data for this study were derived from the U.S. Department of Veterans Affairs administrative database and surgical quality registry. Rheumatoid arthritis patients who underwent a surgical procedure and who were on at least one disease-modifying antirheumatic drug (DMARD) or one biologic agent in the perioperative period during the study period of Oct. 1, 1999, through Sept. 30, 2009, were included. Subjects had a mean age of 67 years, and 91% were men.
The finding that the continuation of DMARD monotherapy or the combination of methotrexate and TNF inhibitor therapy for RA in the perioperative setting was not associated with increased rates of overall postoperative infectious complications and wound infections is important, because many patients are advised to stop taking these drugs prior to surgery because of concerns about increased susceptibility to infection. Discontinuing RA medication can increase the risk of disease flares requiring treatment with prednisone, which can further increase the risk of postsurgical complications, Dr. Juo said.
Clear, consistent guidance on the continuation of treatment among RA patients undergoing surgery has been lacking, she said, noting that guidelines over the years from the ACR, the British Society for Rheumatology, and the Canadian Rheumatology Association have differed in their recommendations.
A new draft guideline reported the morning of Dr. Juo’s presentation at the ACR annual meeting recommended continuing DMARDs but discontinuing biologics prior to surgery, but that guideline is limited to orthopedic surgery among patients with various rheumatic diseases.
“With literature review, the results are conflicting as well; some recommend continuing medication, and others recommend discontinuing medications prior to surgery,” she said.
The current findings, though limited by the study’s observational design and generally older, male population, suggest that continuing antirheumatic medications during the perioperative period is not associated with increased rates of postoperative complications.
“Our study results suggest that discontinuing DMARDs and biologic agents prior to surgery may not be necessary. Therefore, being on DMARDs or biologic agents should not preclude patients from receiving urgent surgeries,” Dr. Juo concluded.
Dr. Juo reported having no disclosures.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Odds ratios for postoperative infection and postoperative wound infection, respectively, were 0.79 and 0.77 with methotrexate continuation, 0.93 and 0.86 with hydroxychloroquine continuation, 0.78 and 0.87 with leflunomide continuation, and 0.35 and 0.38 with combined methotrexate/TNF inhibitor continuation.
Data source: A retrospective review of more than 9,000 surgeries.
Disclosures: Dr. Juo reported having no disclosures.
Urate-lowering therapy poses no harm to kidney function
WASHINGTON – Evidence supporting the renal benefits of urate-lowering therapy in patients with hyperuricemia and gout comes from two separate studies presented at the annual meeting of the American College of Rheumatology.
In the first study, allopurinol did not increase the risk of developing chronic kidney disease (CKD) in newly diagnosed patients with gout and normal or near-normal kidney function. The second study found that urate-lowering therapy (ULT) improved kidney function in patients who already had CKD.
Allopurinol in gout
The study was prompted by the recognition that gout patients are underdiagnosed and undertreated, and even when they have a diagnosis, both patients and primary care physicians who treat the majority of gout patients shy away from ULT.
“Further exacerbating the poor management of gout is the common practice of lowering the dose or stopping allopurinol when a patient with gout begins to have a decline in kidney function, which inevitably adds to the poor control of gout,” Dr. Vargas-Santos explained.
The study was based on electronic health records from the Health Improvement Network (THIN) database that includes patients treated by general practitioners in the United Kingdom. The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who initiated ULT with allopurinol; these patients were compared with 13,608 gout patients (matched by propensity score) in the THIN database who did not start ULT.
Patients were aged 18-89 years (mean age, 58 years) with incident gout diagnosed between 2000 and 2014 who had at least one contact with a general practitioner within a year of study enrollment. The investigators analyzed the relationship between allopurinol use by gout patients and the development of CKD stage 3 or higher.
At a mean follow-up of 4 years, there was no increased risk of developing CKD stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher. The relative risk of developing CKD stage 3 or higher on allopurinol was 1.05, which was not statistically significant. “Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence supports this. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos said.
ULT in CKD
ULT improved kidney function in patients with CKD in a large retrospective study, with the greatest improvement observed in patients with CKD stage 3 and some improvement observed in patients with CKD stage 2. ULT had no benefit in patients with CKD stage 4, suggesting that these patients are too advanced to improve.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of greater than 7 mg/dL and CKD stages 2, 3, and 4 at the index date (the first time this test result was reported). Patients were drawn from the Kaiser Permanente database and treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on ULT and 10,061 were not. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on ULT. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve goal sUA, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate-lowering therapy,” he said. “Stage 4 CDK is too late.”
The authors of both studies had no relevant financial disclosures to report.
WASHINGTON – Evidence supporting the renal benefits of urate-lowering therapy in patients with hyperuricemia and gout comes from two separate studies presented at the annual meeting of the American College of Rheumatology.
In the first study, allopurinol did not increase the risk of developing chronic kidney disease (CKD) in newly diagnosed patients with gout and normal or near-normal kidney function. The second study found that urate-lowering therapy (ULT) improved kidney function in patients who already had CKD.
Allopurinol in gout
The study was prompted by the recognition that gout patients are underdiagnosed and undertreated, and even when they have a diagnosis, both patients and primary care physicians who treat the majority of gout patients shy away from ULT.
“Further exacerbating the poor management of gout is the common practice of lowering the dose or stopping allopurinol when a patient with gout begins to have a decline in kidney function, which inevitably adds to the poor control of gout,” Dr. Vargas-Santos explained.
The study was based on electronic health records from the Health Improvement Network (THIN) database that includes patients treated by general practitioners in the United Kingdom. The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who initiated ULT with allopurinol; these patients were compared with 13,608 gout patients (matched by propensity score) in the THIN database who did not start ULT.
Patients were aged 18-89 years (mean age, 58 years) with incident gout diagnosed between 2000 and 2014 who had at least one contact with a general practitioner within a year of study enrollment. The investigators analyzed the relationship between allopurinol use by gout patients and the development of CKD stage 3 or higher.
At a mean follow-up of 4 years, there was no increased risk of developing CKD stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher. The relative risk of developing CKD stage 3 or higher on allopurinol was 1.05, which was not statistically significant. “Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence supports this. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos said.
ULT in CKD
ULT improved kidney function in patients with CKD in a large retrospective study, with the greatest improvement observed in patients with CKD stage 3 and some improvement observed in patients with CKD stage 2. ULT had no benefit in patients with CKD stage 4, suggesting that these patients are too advanced to improve.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of greater than 7 mg/dL and CKD stages 2, 3, and 4 at the index date (the first time this test result was reported). Patients were drawn from the Kaiser Permanente database and treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on ULT and 10,061 were not. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on ULT. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve goal sUA, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate-lowering therapy,” he said. “Stage 4 CDK is too late.”
The authors of both studies had no relevant financial disclosures to report.
WASHINGTON – Evidence supporting the renal benefits of urate-lowering therapy in patients with hyperuricemia and gout comes from two separate studies presented at the annual meeting of the American College of Rheumatology.
In the first study, allopurinol did not increase the risk of developing chronic kidney disease (CKD) in newly diagnosed patients with gout and normal or near-normal kidney function. The second study found that urate-lowering therapy (ULT) improved kidney function in patients who already had CKD.
Allopurinol in gout
The study was prompted by the recognition that gout patients are underdiagnosed and undertreated, and even when they have a diagnosis, both patients and primary care physicians who treat the majority of gout patients shy away from ULT.
“Further exacerbating the poor management of gout is the common practice of lowering the dose or stopping allopurinol when a patient with gout begins to have a decline in kidney function, which inevitably adds to the poor control of gout,” Dr. Vargas-Santos explained.
The study was based on electronic health records from the Health Improvement Network (THIN) database that includes patients treated by general practitioners in the United Kingdom. The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who initiated ULT with allopurinol; these patients were compared with 13,608 gout patients (matched by propensity score) in the THIN database who did not start ULT.
Patients were aged 18-89 years (mean age, 58 years) with incident gout diagnosed between 2000 and 2014 who had at least one contact with a general practitioner within a year of study enrollment. The investigators analyzed the relationship between allopurinol use by gout patients and the development of CKD stage 3 or higher.
At a mean follow-up of 4 years, there was no increased risk of developing CKD stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher. The relative risk of developing CKD stage 3 or higher on allopurinol was 1.05, which was not statistically significant. “Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence supports this. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos said.
ULT in CKD
ULT improved kidney function in patients with CKD in a large retrospective study, with the greatest improvement observed in patients with CKD stage 3 and some improvement observed in patients with CKD stage 2. ULT had no benefit in patients with CKD stage 4, suggesting that these patients are too advanced to improve.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of greater than 7 mg/dL and CKD stages 2, 3, and 4 at the index date (the first time this test result was reported). Patients were drawn from the Kaiser Permanente database and treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on ULT and 10,061 were not. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on ULT. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve goal sUA, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate-lowering therapy,” he said. “Stage 4 CDK is too late.”
The authors of both studies had no relevant financial disclosures to report.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The first study found that allopurinol did not increase the risk of developing CKD stage 3 or higher in gout patients with normal or near-normal kidney function. The second study found that reaching goal with urate-lowering therapy led to improved kidney function, especially in patients with stage 3 CKD.
Data source: Two population-based studies based on the U.K.’s THIN database. The first included 13,608 patients and 13,608 matched controls. The second study included 12,751 patients with serum urate levels of greater than 7 mg/dL.
Disclosures: The authors of both studies had no relevant financial disclosures to report.
VIDEO: Celecoxib just as safe as naproxen or ibuprofen in OA and RA
WASHINGTON – Celecoxib conferred a 53% decreased risk of overall mortality upon patients with rheumatoid arthritis when compared with naproxen – a surprise finding in a subanalysis of the newly released PRECISION study of anti-inflammatory drugs in arthritis.
But it’s tough to know what to make of the difference, according to the investigators at the annual meeting of the American College of Rheumatology. Although statistically significant, the mortality finding was based on just 45 events: 30 among those taking naproxen and 15 among those taking celecoxib.
“While I would say we were surprised to see this, we really can’t say what it means – or if it means anything,” primary investigator Daniel Solomon, MD, said in an interview. “This is a finding we will continue to investigate and look at, but at this point it’s not enough to base any prescribing decisions on.”
PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen) enrolled more than 24,000 patients with osteoarthritis or rheumatoid arthritis. They were randomized to celecoxib, naproxen, or ibuprofen for a mean of 20 months, with an additional mean follow-up of 34 months.
The primary outcome was the first occurrence of an adverse event from the Antiplatelet Trialists Collaboration criteria (APTC; death from cardiovascular causes, nonfatal heart attack, or nonfatal stroke). Secondary outcomes included:
• Major cardiovascular events (heart attack, stroke, cardiovascular death, revascularization, and hospitalization for unstable angina or transient ischemic attack).
• Renal events (acute kidney injury, including hospitalization for renal failure).
• Gastrointestinal events (hemorrhage, perforation, gastroduodenal ulcer, anemia of gastrointestinal origin, and gastric outlet obstruction.
The main PRECISION findings were released Nov. 13 at the annual meeting of the American Heart Association and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2016 Nov 13. doi: 10.1056/NEJMoa1611593).
Overall, celecoxib was just as safe as were the other drugs on the APTC endpoint, which occurred in about 2% of each groups. The study found significantly decreased risks of both GI and renal events with celecoxib, compared with either naproxen or ibuprofen. Celecoxib and naproxen were equivalent with regard to GI and renal events.
The subanalysis, released at the ACR meeting, adds important disease-specific context to the overall PRECISION results.
“We wanted to really delve into the subtle differences in how these two patient groups responded to these medications,” said PRECISION coinvestigator Elaine Husni, MD, vice chair of the department of rheumatic and immunologic diseases at the Cleveland Clinic.
“We learned that each of these NSAIDs has a unique safety profile that can be different in different groups. And in general, celecoxib seems less risky than the others.”
The cohort subanalysis broke down these endpoints among 21,600 patients with osteoarthritis and 2,400 with rheumatoid arthritis.
Among patients with osteoarthritis, celecoxib was also associated with a 16% decreased risk of a major adverse cardiovascular event, compared with ibuprofen. GI events were also less likely in this group: Celecoxib was associated with a 32% decreased risk, compared with ibuprofen, and a 27% decreased risk, compared with naproxen.
Renal outcomes were almost identical in all of the medications in both groups, Dr. Husni said.
In addition to the adverse event outcomes, the subanalysis examined how well patients responded to their assigned NSAID. There were also some subtle differences seen here, Dr. Solomon and Dr. Husni said.
For patients with RA, ibuprofen was slightly, but significantly, more effective than either celecoxib or ibuprofen at controlling pain as measured by a visual analog pain scale. Patients with osteoarthritis responded equally well to all of the drugs.
RA patients also responded best to ibuprofen as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). Again, patients with osteoarthritis responded equally well to all of the medications.
The overall findings, as well as the subanalysis, should be reassuring to both physicians and patients, said Dr. Solomon, chief of the section of clinical sciences in the divisions of rheumatology and pharmacoepidemiology at Brigham and Women’s Hospital, Boston.
“I can now stand in front of patients and say with confidence, ‘Each of these drugs is fairly safe, and together we can choose the one that will be best for you, based on your own individual history and your own individual risk factors.’ I feel good about that.”
Pfizer funded the trial. Dr. Husni has research grants from Genzyme/Sanofi on a knee osteoarthritis trial related to hyaluronic acid injections. Dr. Solomon has research grants from Pfizer on non-NSAID related topics. He also receives royalties from UpToDate on chapters related to NSAIDs and selective COX-2 inhibitors.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Celecoxib conferred a 53% decreased risk of overall mortality upon patients with rheumatoid arthritis when compared with naproxen – a surprise finding in a subanalysis of the newly released PRECISION study of anti-inflammatory drugs in arthritis.
But it’s tough to know what to make of the difference, according to the investigators at the annual meeting of the American College of Rheumatology. Although statistically significant, the mortality finding was based on just 45 events: 30 among those taking naproxen and 15 among those taking celecoxib.
“While I would say we were surprised to see this, we really can’t say what it means – or if it means anything,” primary investigator Daniel Solomon, MD, said in an interview. “This is a finding we will continue to investigate and look at, but at this point it’s not enough to base any prescribing decisions on.”
PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen) enrolled more than 24,000 patients with osteoarthritis or rheumatoid arthritis. They were randomized to celecoxib, naproxen, or ibuprofen for a mean of 20 months, with an additional mean follow-up of 34 months.
The primary outcome was the first occurrence of an adverse event from the Antiplatelet Trialists Collaboration criteria (APTC; death from cardiovascular causes, nonfatal heart attack, or nonfatal stroke). Secondary outcomes included:
• Major cardiovascular events (heart attack, stroke, cardiovascular death, revascularization, and hospitalization for unstable angina or transient ischemic attack).
• Renal events (acute kidney injury, including hospitalization for renal failure).
• Gastrointestinal events (hemorrhage, perforation, gastroduodenal ulcer, anemia of gastrointestinal origin, and gastric outlet obstruction.
The main PRECISION findings were released Nov. 13 at the annual meeting of the American Heart Association and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2016 Nov 13. doi: 10.1056/NEJMoa1611593).
Overall, celecoxib was just as safe as were the other drugs on the APTC endpoint, which occurred in about 2% of each groups. The study found significantly decreased risks of both GI and renal events with celecoxib, compared with either naproxen or ibuprofen. Celecoxib and naproxen were equivalent with regard to GI and renal events.
The subanalysis, released at the ACR meeting, adds important disease-specific context to the overall PRECISION results.
“We wanted to really delve into the subtle differences in how these two patient groups responded to these medications,” said PRECISION coinvestigator Elaine Husni, MD, vice chair of the department of rheumatic and immunologic diseases at the Cleveland Clinic.
“We learned that each of these NSAIDs has a unique safety profile that can be different in different groups. And in general, celecoxib seems less risky than the others.”
The cohort subanalysis broke down these endpoints among 21,600 patients with osteoarthritis and 2,400 with rheumatoid arthritis.
Among patients with osteoarthritis, celecoxib was also associated with a 16% decreased risk of a major adverse cardiovascular event, compared with ibuprofen. GI events were also less likely in this group: Celecoxib was associated with a 32% decreased risk, compared with ibuprofen, and a 27% decreased risk, compared with naproxen.
Renal outcomes were almost identical in all of the medications in both groups, Dr. Husni said.
In addition to the adverse event outcomes, the subanalysis examined how well patients responded to their assigned NSAID. There were also some subtle differences seen here, Dr. Solomon and Dr. Husni said.
For patients with RA, ibuprofen was slightly, but significantly, more effective than either celecoxib or ibuprofen at controlling pain as measured by a visual analog pain scale. Patients with osteoarthritis responded equally well to all of the drugs.
RA patients also responded best to ibuprofen as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). Again, patients with osteoarthritis responded equally well to all of the medications.
The overall findings, as well as the subanalysis, should be reassuring to both physicians and patients, said Dr. Solomon, chief of the section of clinical sciences in the divisions of rheumatology and pharmacoepidemiology at Brigham and Women’s Hospital, Boston.
“I can now stand in front of patients and say with confidence, ‘Each of these drugs is fairly safe, and together we can choose the one that will be best for you, based on your own individual history and your own individual risk factors.’ I feel good about that.”
Pfizer funded the trial. Dr. Husni has research grants from Genzyme/Sanofi on a knee osteoarthritis trial related to hyaluronic acid injections. Dr. Solomon has research grants from Pfizer on non-NSAID related topics. He also receives royalties from UpToDate on chapters related to NSAIDs and selective COX-2 inhibitors.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
WASHINGTON – Celecoxib conferred a 53% decreased risk of overall mortality upon patients with rheumatoid arthritis when compared with naproxen – a surprise finding in a subanalysis of the newly released PRECISION study of anti-inflammatory drugs in arthritis.
But it’s tough to know what to make of the difference, according to the investigators at the annual meeting of the American College of Rheumatology. Although statistically significant, the mortality finding was based on just 45 events: 30 among those taking naproxen and 15 among those taking celecoxib.
“While I would say we were surprised to see this, we really can’t say what it means – or if it means anything,” primary investigator Daniel Solomon, MD, said in an interview. “This is a finding we will continue to investigate and look at, but at this point it’s not enough to base any prescribing decisions on.”
PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen) enrolled more than 24,000 patients with osteoarthritis or rheumatoid arthritis. They were randomized to celecoxib, naproxen, or ibuprofen for a mean of 20 months, with an additional mean follow-up of 34 months.
The primary outcome was the first occurrence of an adverse event from the Antiplatelet Trialists Collaboration criteria (APTC; death from cardiovascular causes, nonfatal heart attack, or nonfatal stroke). Secondary outcomes included:
• Major cardiovascular events (heart attack, stroke, cardiovascular death, revascularization, and hospitalization for unstable angina or transient ischemic attack).
• Renal events (acute kidney injury, including hospitalization for renal failure).
• Gastrointestinal events (hemorrhage, perforation, gastroduodenal ulcer, anemia of gastrointestinal origin, and gastric outlet obstruction.
The main PRECISION findings were released Nov. 13 at the annual meeting of the American Heart Association and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2016 Nov 13. doi: 10.1056/NEJMoa1611593).
Overall, celecoxib was just as safe as were the other drugs on the APTC endpoint, which occurred in about 2% of each groups. The study found significantly decreased risks of both GI and renal events with celecoxib, compared with either naproxen or ibuprofen. Celecoxib and naproxen were equivalent with regard to GI and renal events.
The subanalysis, released at the ACR meeting, adds important disease-specific context to the overall PRECISION results.
“We wanted to really delve into the subtle differences in how these two patient groups responded to these medications,” said PRECISION coinvestigator Elaine Husni, MD, vice chair of the department of rheumatic and immunologic diseases at the Cleveland Clinic.
“We learned that each of these NSAIDs has a unique safety profile that can be different in different groups. And in general, celecoxib seems less risky than the others.”
The cohort subanalysis broke down these endpoints among 21,600 patients with osteoarthritis and 2,400 with rheumatoid arthritis.
Among patients with osteoarthritis, celecoxib was also associated with a 16% decreased risk of a major adverse cardiovascular event, compared with ibuprofen. GI events were also less likely in this group: Celecoxib was associated with a 32% decreased risk, compared with ibuprofen, and a 27% decreased risk, compared with naproxen.
Renal outcomes were almost identical in all of the medications in both groups, Dr. Husni said.
In addition to the adverse event outcomes, the subanalysis examined how well patients responded to their assigned NSAID. There were also some subtle differences seen here, Dr. Solomon and Dr. Husni said.
For patients with RA, ibuprofen was slightly, but significantly, more effective than either celecoxib or ibuprofen at controlling pain as measured by a visual analog pain scale. Patients with osteoarthritis responded equally well to all of the drugs.
RA patients also responded best to ibuprofen as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). Again, patients with osteoarthritis responded equally well to all of the medications.
The overall findings, as well as the subanalysis, should be reassuring to both physicians and patients, said Dr. Solomon, chief of the section of clinical sciences in the divisions of rheumatology and pharmacoepidemiology at Brigham and Women’s Hospital, Boston.
“I can now stand in front of patients and say with confidence, ‘Each of these drugs is fairly safe, and together we can choose the one that will be best for you, based on your own individual history and your own individual risk factors.’ I feel good about that.”
Pfizer funded the trial. Dr. Husni has research grants from Genzyme/Sanofi on a knee osteoarthritis trial related to hyaluronic acid injections. Dr. Solomon has research grants from Pfizer on non-NSAID related topics. He also receives royalties from UpToDate on chapters related to NSAIDs and selective COX-2 inhibitors.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
msullivan@frontlinemedcom.com
On Twitter @alz_gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Compared with naproxen, celecoxib was associated with a 53% lower risk of overall mortality, although the clinical impact of that finding remains unknown.
Data source: PRECISION, which randomized more than 24,000 patients to celecoxib, ibuprofen, or naproxen.
Disclosures: Pfizer funded the trial. Dr. Husni has research grants from Genzyme/Sanofi on a knee osteoarthritis trial related to hyaluronic acid injections. Dr. Solomon has research grants from Pfizer on non-NSAID related topics. He also receives royalties from UpToDate on chapters related to NSAIDs and selective COX-2 inhibitors.
Tocilizumab makes big impression in giant cell arteritis treatment
WASHINGTON – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.
The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.
Tocilizumab, an IL-6 receptor-alpha inhibitor, is approved by the Food and Drug Administration for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis.
The difficulty in treating GCA is made evident by the fact that “at least 10% of patients with GCA lose their vision, and the long-term morbidity of glucocorticoid treatment – the only treatment thus far for this disease – is substantial,” he said. “For more than 65 years, no true steroid-sparing treatment has been proven effective.”
Remissions rise while flares and steroid use decline
GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.
“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.
Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).
Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.
Investigators were blinded to the prednisone taper regimen and the treatment.
Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.
The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.
“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.
The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.
Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.
“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.
According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.
There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.
“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.
Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.
WASHINGTON – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.
The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.
Tocilizumab, an IL-6 receptor-alpha inhibitor, is approved by the Food and Drug Administration for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis.
The difficulty in treating GCA is made evident by the fact that “at least 10% of patients with GCA lose their vision, and the long-term morbidity of glucocorticoid treatment – the only treatment thus far for this disease – is substantial,” he said. “For more than 65 years, no true steroid-sparing treatment has been proven effective.”
Remissions rise while flares and steroid use decline
GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.
“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.
Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).
Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.
Investigators were blinded to the prednisone taper regimen and the treatment.
Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.
The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.
“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.
The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.
Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.
“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.
According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.
There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.
“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.
Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.
WASHINGTON – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.
The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.
Tocilizumab, an IL-6 receptor-alpha inhibitor, is approved by the Food and Drug Administration for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis.
The difficulty in treating GCA is made evident by the fact that “at least 10% of patients with GCA lose their vision, and the long-term morbidity of glucocorticoid treatment – the only treatment thus far for this disease – is substantial,” he said. “For more than 65 years, no true steroid-sparing treatment has been proven effective.”
Remissions rise while flares and steroid use decline
GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.
“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.
Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).
Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.
Investigators were blinded to the prednisone taper regimen and the treatment.
Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.
The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.
“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.
The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.
Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.
“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.
According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.
There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.
“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.
Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The rate of sustained remission at 52 weeks was 56% with tocilizumab versus 14% for short course prednisone and 18% for long-course prednisone.
Data source: Randomized, double-blind, placebo-controlled trial of 251 patients.
Disclosures: Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.
VIDEO: Cardiac inflammation present in RA patients, but resolves with RA therapy
WASHINGTON – Chronic cardiac inflammation is present in rheumatoid arthritis patients and appears to resolve when they achieve a good clinical response to medical therapy.
The findings of two cardiac imaging studies offer a tantalizing clue to the link between RA and heart failure, said Isabelle Amigues, MD, who reported the findings at the annual meeting of the American College of Rheumatology.
“We know that the inflammation of RA is not just restricted to joints,” said Dr. Amigues, a rheumatology fellow at Columbia University, New York. “We see it throughout the body, so of course it makes sense that we would see it in the heart as well. And now we see that we may be able to manage this with good disease management.
The study that found improvement of myocarditis with RA therapy was very small – just 8 patients and 12 controls – but the results were surprising and encouraging, Dr. Amigues said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The initial study examined chronic myocarditis in 119 patients with active RA; most (76%) were positive for anti-cyclic citrullinated peptides. They had a mean disease duration of 7 years. The mean Disease Activity Score was 3.8; 28% had low disease activity. About a third of the patients were taking a tumor necrosis factor inhibitor.
These patients were age- and gender-matched with 13 controls who did not have RA. All underwent cardiac FDG-PET scans as a marker of inflammation, as well as 3-D echocardiography to assess left ventricular mass and volume, and both systolic and diastolic function.
The maximum standard uptake value (SUVmax) in the scans was 12% higher in study patients than in the controls. This finding was associated with a higher body mass index and moderate to severe disease activity. After adjustment for BMI and RA treatment, the mean SUVmax was 30% higher for the patients with moderate to severe disease activity than in those who had low disease activity. Patients taking non-TNF biologics had 35% less cardiac inflammation than did those taking a TNF inhibitor or those not taking a biologic.
There were no significant associations with age, gender, race, diabetes, C-reactive protein or IL-6, coronary flow reserve, or coronary calcium. Inflammation was not related to any measure of cardiac structure or function on echocardiography.
“This finding makes sense, because we know that RA causes systemic inflammation, so it’s not surprising to see inflammation at the level of the heart,” Dr. Amigues said in an interview. “We do need longitudinal studies though to determine if structural or functional changes occur later on in the disease process.”
While the initial study didn’t look at cardiac changes in the disease process, Dr. Amigues’ subsequent study did find these associated with successful RA treatment. This follow-up study comprised eight patients who underwent PET scans and 3-D echocardiography at baseline and 6 months after initiation of a step-up treatment regimen. These were compared to 12 age- and gender-matched controls without RA, who had one baseline scan.
Most patients (87%) were women; their mean age was 62 years, and mean disease duration, 5 months. Most of the patients received TNF inhibitors with methotrexate as their step-up therapy; the rest were given triple therapy.
At the baseline scan, mean SUVmax was significantly higher in the patients than in controls (7.2 vs. 3.4 units). After 6 months of treatment, the mean DAS28 score among patients had decreased more than 1 point (4.57-3.51). Their mean SUVmax had also decreased to the level seen in controls. This was a significant improvement, Dr. Amigues said.
Again, there were no structural or functional differences between the two groups at baseline or follow-up, suggesting that cardiac inflammation is not inducing structural change – at least early in the RA disease process, Dr. Amigues said.
She reported having no relevant financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
WASHINGTON – Chronic cardiac inflammation is present in rheumatoid arthritis patients and appears to resolve when they achieve a good clinical response to medical therapy.
The findings of two cardiac imaging studies offer a tantalizing clue to the link between RA and heart failure, said Isabelle Amigues, MD, who reported the findings at the annual meeting of the American College of Rheumatology.
“We know that the inflammation of RA is not just restricted to joints,” said Dr. Amigues, a rheumatology fellow at Columbia University, New York. “We see it throughout the body, so of course it makes sense that we would see it in the heart as well. And now we see that we may be able to manage this with good disease management.
The study that found improvement of myocarditis with RA therapy was very small – just 8 patients and 12 controls – but the results were surprising and encouraging, Dr. Amigues said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The initial study examined chronic myocarditis in 119 patients with active RA; most (76%) were positive for anti-cyclic citrullinated peptides. They had a mean disease duration of 7 years. The mean Disease Activity Score was 3.8; 28% had low disease activity. About a third of the patients were taking a tumor necrosis factor inhibitor.
These patients were age- and gender-matched with 13 controls who did not have RA. All underwent cardiac FDG-PET scans as a marker of inflammation, as well as 3-D echocardiography to assess left ventricular mass and volume, and both systolic and diastolic function.
The maximum standard uptake value (SUVmax) in the scans was 12% higher in study patients than in the controls. This finding was associated with a higher body mass index and moderate to severe disease activity. After adjustment for BMI and RA treatment, the mean SUVmax was 30% higher for the patients with moderate to severe disease activity than in those who had low disease activity. Patients taking non-TNF biologics had 35% less cardiac inflammation than did those taking a TNF inhibitor or those not taking a biologic.
There were no significant associations with age, gender, race, diabetes, C-reactive protein or IL-6, coronary flow reserve, or coronary calcium. Inflammation was not related to any measure of cardiac structure or function on echocardiography.
“This finding makes sense, because we know that RA causes systemic inflammation, so it’s not surprising to see inflammation at the level of the heart,” Dr. Amigues said in an interview. “We do need longitudinal studies though to determine if structural or functional changes occur later on in the disease process.”
While the initial study didn’t look at cardiac changes in the disease process, Dr. Amigues’ subsequent study did find these associated with successful RA treatment. This follow-up study comprised eight patients who underwent PET scans and 3-D echocardiography at baseline and 6 months after initiation of a step-up treatment regimen. These were compared to 12 age- and gender-matched controls without RA, who had one baseline scan.
Most patients (87%) were women; their mean age was 62 years, and mean disease duration, 5 months. Most of the patients received TNF inhibitors with methotrexate as their step-up therapy; the rest were given triple therapy.
At the baseline scan, mean SUVmax was significantly higher in the patients than in controls (7.2 vs. 3.4 units). After 6 months of treatment, the mean DAS28 score among patients had decreased more than 1 point (4.57-3.51). Their mean SUVmax had also decreased to the level seen in controls. This was a significant improvement, Dr. Amigues said.
Again, there were no structural or functional differences between the two groups at baseline or follow-up, suggesting that cardiac inflammation is not inducing structural change – at least early in the RA disease process, Dr. Amigues said.
She reported having no relevant financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
WASHINGTON – Chronic cardiac inflammation is present in rheumatoid arthritis patients and appears to resolve when they achieve a good clinical response to medical therapy.
The findings of two cardiac imaging studies offer a tantalizing clue to the link between RA and heart failure, said Isabelle Amigues, MD, who reported the findings at the annual meeting of the American College of Rheumatology.
“We know that the inflammation of RA is not just restricted to joints,” said Dr. Amigues, a rheumatology fellow at Columbia University, New York. “We see it throughout the body, so of course it makes sense that we would see it in the heart as well. And now we see that we may be able to manage this with good disease management.
The study that found improvement of myocarditis with RA therapy was very small – just 8 patients and 12 controls – but the results were surprising and encouraging, Dr. Amigues said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The initial study examined chronic myocarditis in 119 patients with active RA; most (76%) were positive for anti-cyclic citrullinated peptides. They had a mean disease duration of 7 years. The mean Disease Activity Score was 3.8; 28% had low disease activity. About a third of the patients were taking a tumor necrosis factor inhibitor.
These patients were age- and gender-matched with 13 controls who did not have RA. All underwent cardiac FDG-PET scans as a marker of inflammation, as well as 3-D echocardiography to assess left ventricular mass and volume, and both systolic and diastolic function.
The maximum standard uptake value (SUVmax) in the scans was 12% higher in study patients than in the controls. This finding was associated with a higher body mass index and moderate to severe disease activity. After adjustment for BMI and RA treatment, the mean SUVmax was 30% higher for the patients with moderate to severe disease activity than in those who had low disease activity. Patients taking non-TNF biologics had 35% less cardiac inflammation than did those taking a TNF inhibitor or those not taking a biologic.
There were no significant associations with age, gender, race, diabetes, C-reactive protein or IL-6, coronary flow reserve, or coronary calcium. Inflammation was not related to any measure of cardiac structure or function on echocardiography.
“This finding makes sense, because we know that RA causes systemic inflammation, so it’s not surprising to see inflammation at the level of the heart,” Dr. Amigues said in an interview. “We do need longitudinal studies though to determine if structural or functional changes occur later on in the disease process.”
While the initial study didn’t look at cardiac changes in the disease process, Dr. Amigues’ subsequent study did find these associated with successful RA treatment. This follow-up study comprised eight patients who underwent PET scans and 3-D echocardiography at baseline and 6 months after initiation of a step-up treatment regimen. These were compared to 12 age- and gender-matched controls without RA, who had one baseline scan.
Most patients (87%) were women; their mean age was 62 years, and mean disease duration, 5 months. Most of the patients received TNF inhibitors with methotrexate as their step-up therapy; the rest were given triple therapy.
At the baseline scan, mean SUVmax was significantly higher in the patients than in controls (7.2 vs. 3.4 units). After 6 months of treatment, the mean DAS28 score among patients had decreased more than 1 point (4.57-3.51). Their mean SUVmax had also decreased to the level seen in controls. This was a significant improvement, Dr. Amigues said.
Again, there were no structural or functional differences between the two groups at baseline or follow-up, suggesting that cardiac inflammation is not inducing structural change – at least early in the RA disease process, Dr. Amigues said.
She reported having no relevant financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_Gal
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: PET imaging showed 12% more inflammatory activity in the hearts of patients than in those of controls; this decreased significantly as disease activity remitted with treatment.
Data source: The myocarditis study comprised 119 patients; the therapeutic response study comprised 8 patients and 12 controls.
Disclosures: Dr. Amigues reported having no relevant financial disclosures.
VIDEO: Allopurinol may not raise kidney disease risk in gout
WASHINGTON – Urate-lowering therapy (ULT) with allopurinol does not appear to increase the risk of chronic kidney disease in patients with gout who have normal or near-normal kidney function at diagnosis, according to a large retrospective study presented at the annual meeting of the American College of Rheumatology.
The study was based on electronic health records from The Health Improvement Network (THIN), a database that includes patients treated by general practitioners in the United Kingdom.
“It is sad in my practice to see how many gout patients are not treated with ULT because patients fear the side effects of medication or just don’t want to be treated, especially when they are not in flare. Many general practitioners also don’t view gout as a serious condition requiring medication,” said lead author Ana Beatriz Vargas-Santos, PhD, a research fellow at Boston University and a rheumatologist at the State University of Rio de Janeiro in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who started ULT)with allopurinol and compared them with 13,608 gout patients in the THIN database who did not start ULT.
At a mean follow-up of 4 years, there was no increased risk of developing chronic kidney disease (CKD) stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher.
“Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence is in the same direction. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos stated.
Dr. Vargas-Santos had no financial disclosures.
WASHINGTON – Urate-lowering therapy (ULT) with allopurinol does not appear to increase the risk of chronic kidney disease in patients with gout who have normal or near-normal kidney function at diagnosis, according to a large retrospective study presented at the annual meeting of the American College of Rheumatology.
The study was based on electronic health records from The Health Improvement Network (THIN), a database that includes patients treated by general practitioners in the United Kingdom.
“It is sad in my practice to see how many gout patients are not treated with ULT because patients fear the side effects of medication or just don’t want to be treated, especially when they are not in flare. Many general practitioners also don’t view gout as a serious condition requiring medication,” said lead author Ana Beatriz Vargas-Santos, PhD, a research fellow at Boston University and a rheumatologist at the State University of Rio de Janeiro in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who started ULT)with allopurinol and compared them with 13,608 gout patients in the THIN database who did not start ULT.
At a mean follow-up of 4 years, there was no increased risk of developing chronic kidney disease (CKD) stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher.
“Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence is in the same direction. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos stated.
Dr. Vargas-Santos had no financial disclosures.
WASHINGTON – Urate-lowering therapy (ULT) with allopurinol does not appear to increase the risk of chronic kidney disease in patients with gout who have normal or near-normal kidney function at diagnosis, according to a large retrospective study presented at the annual meeting of the American College of Rheumatology.
The study was based on electronic health records from The Health Improvement Network (THIN), a database that includes patients treated by general practitioners in the United Kingdom.
“It is sad in my practice to see how many gout patients are not treated with ULT because patients fear the side effects of medication or just don’t want to be treated, especially when they are not in flare. Many general practitioners also don’t view gout as a serious condition requiring medication,” said lead author Ana Beatriz Vargas-Santos, PhD, a research fellow at Boston University and a rheumatologist at the State University of Rio de Janeiro in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who started ULT)with allopurinol and compared them with 13,608 gout patients in the THIN database who did not start ULT.
At a mean follow-up of 4 years, there was no increased risk of developing chronic kidney disease (CKD) stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher.
“Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence is in the same direction. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos stated.
Dr. Vargas-Santos had no financial disclosures.
AT THE ACR ANNUAL MEETING
Rheumatology malpractice litigation investigated for first time
WASHINGTON – Failure to diagnose and a failure to treat in a timely manner were the two most commonly alleged malpractice claims in an analysis of rheumatic disease–related cases presented at the annual meeting of the American College of Rheumatology.
The study of 20 rheumatic disease cases during a 31-year period is thought by the investigators to be the first analysis of malpractice litigation in rheumatology.
Rheumatologists accounted for one-third of all named defendants in the 20 cases, which constituted a convenience sample. They excluded 10 cases because of duplication or lack of relevance to rheumatology. They searched the online legal database WestLaw using the terms “rheumatology” and “medical malpractice” to find all state and federal jury verdicts and settlements related to rheumatology during 1985-2015. The 20 cases occurred in 10 states. The plaintiffs had a mean age of about 52 years, and 45% were female.
Plaintiffs in the medical malpractice suits won only four of the cases, but those had a mean payout of about $2.78 million, which Mr. Prabhu described as lower than what’s been reported in other specialties that he and his colleagues are investigating, such as oncology and neurosurgery. The jury found in favor of the defendant in 12 of the cases, and in 3 cases the parties reached a settlement in which most payouts were not disclosed. The verdict was undisclosed in one case.
Mr. Prabhu said that the investigators discovered an additional 34 cases in their search of the database that they plan on characterizing in another study.
The researchers reported having no relevant financial disclosures.
WASHINGTON – Failure to diagnose and a failure to treat in a timely manner were the two most commonly alleged malpractice claims in an analysis of rheumatic disease–related cases presented at the annual meeting of the American College of Rheumatology.
The study of 20 rheumatic disease cases during a 31-year period is thought by the investigators to be the first analysis of malpractice litigation in rheumatology.
Rheumatologists accounted for one-third of all named defendants in the 20 cases, which constituted a convenience sample. They excluded 10 cases because of duplication or lack of relevance to rheumatology. They searched the online legal database WestLaw using the terms “rheumatology” and “medical malpractice” to find all state and federal jury verdicts and settlements related to rheumatology during 1985-2015. The 20 cases occurred in 10 states. The plaintiffs had a mean age of about 52 years, and 45% were female.
Plaintiffs in the medical malpractice suits won only four of the cases, but those had a mean payout of about $2.78 million, which Mr. Prabhu described as lower than what’s been reported in other specialties that he and his colleagues are investigating, such as oncology and neurosurgery. The jury found in favor of the defendant in 12 of the cases, and in 3 cases the parties reached a settlement in which most payouts were not disclosed. The verdict was undisclosed in one case.
Mr. Prabhu said that the investigators discovered an additional 34 cases in their search of the database that they plan on characterizing in another study.
The researchers reported having no relevant financial disclosures.
WASHINGTON – Failure to diagnose and a failure to treat in a timely manner were the two most commonly alleged malpractice claims in an analysis of rheumatic disease–related cases presented at the annual meeting of the American College of Rheumatology.
The study of 20 rheumatic disease cases during a 31-year period is thought by the investigators to be the first analysis of malpractice litigation in rheumatology.
Rheumatologists accounted for one-third of all named defendants in the 20 cases, which constituted a convenience sample. They excluded 10 cases because of duplication or lack of relevance to rheumatology. They searched the online legal database WestLaw using the terms “rheumatology” and “medical malpractice” to find all state and federal jury verdicts and settlements related to rheumatology during 1985-2015. The 20 cases occurred in 10 states. The plaintiffs had a mean age of about 52 years, and 45% were female.
Plaintiffs in the medical malpractice suits won only four of the cases, but those had a mean payout of about $2.78 million, which Mr. Prabhu described as lower than what’s been reported in other specialties that he and his colleagues are investigating, such as oncology and neurosurgery. The jury found in favor of the defendant in 12 of the cases, and in 3 cases the parties reached a settlement in which most payouts were not disclosed. The verdict was undisclosed in one case.
Mr. Prabhu said that the investigators discovered an additional 34 cases in their search of the database that they plan on characterizing in another study.
The researchers reported having no relevant financial disclosures.
Key clinical point:
Major finding: Plaintiffs in the malpractice suits won only 20% of the cases, but those had a mean payout of about $2.78 million.
Data source: A retrospective study of 20 rheumatic disease malpractice cases occurring in 1985-2015.
Disclosures: The researchers reported having no relevant financial disclosures.
Genetic markers may predict response to biologics in rheumatoid arthritis
WASHINGTON – Three gene expression markers appear to predict response to some of the most common and powerful rheumatoid arthritis drugs employed in clinical practice.
In the largest gene-expression study of these drugs to date, researchers from Glasgow found 23 genes that predicted response to TNF inhibitors, and 23 more that predicted response to rituximab. They also found eight genes that predicted positive response to both types of drugs.
Just as important, the team found that 10% of patients in the study had none of the markers, Duncan Porter, MD, said during a press briefing at the annual meeting of the American College of Rheumatology.
If confirmed in independent validation cohorts, the findings could revolutionize medical therapy for rheumatoid arthritis, Dr. Porter said in an interview.
“Right now, the choice of treatment is mostly a flip of the coin,” said Dr. Porter, a rheumatologist at Queen Elizabeth University Hospital in Glasgow. “We don’t have a lot of comparative data to support one drug over the other, and most head-to-head studies show noninferiority.
“So, it would be ideal to be able to identify patients who will respond to one class or the other, and give them the right medicine the first time,” he noted. “If we can do that, we have the beginnings of really meaningful personalized therapy in RA.”
Dr. Porter reported a transcriptome-wide association study of 250 patients with RA who were enrolled in the ORBIT trial (Lancet. 2016 Jul 16;388[10041]:239-47). Dr. Porter was the study’s primary investigator.
ORBIT comprised 295 patients with active, seropositive rheumatoid arthritis who had failed disease-modifying antirheumatic therapy. They were randomized to B-cell depletion with rituximab or to the TNF inhibitors adalimumab or etanercept. ORBIT concluded that clinical response was similar with all three drugs. However, while most patients did well on their assigned drug, no matter which class, 20% failed their initial assignment.
The genetic study examined RNA transcripts in whole blood samples among a subset of the ORBIT patients. Most of the samples (70%) were used to identify markers and created a prediction model; that was then verified in the remaining 30% of samples. Markers were correlated to clinical response associated with rituximab and TNF inhibition. Clinical response was defined as a 1.2-point decline in the Disease Activity Score from baseline to 3 months of therapy.
At least 1 of the 54 genetic response markers was present in 90% of the population; 50% would have responded well to either drug, or 40% to just one of them.
But 10% of the population lacked either of the response markers – a very important finding, Dr. Porter noted, because if identified early, these patients could potentially avoid ineffective medication trials.
The markers’ predictive values were uniformly high, with a sensitivity of 93% and specificity of 91%. The positive predictive value was 96%, and the negative predictive value was 86%. Patients predicted to respond at 3 months were also more likely to have a good response (43% vs. 23%) or remission (23% vs. 10%), as measured by the Disease Activity Score 28 at 12 months.
While Dr. Porter was excited about the findings, he eyed them cautiously.
“The landscape is littered with biomarkers that had great early promise but failed in later validation studies,” he said. “We must be very careful in interpreting this. However, the other response studies have been small, and have not compared two drugs. This study was large with robust results, so we are encouraged.”
Dr Porter is now designing the protocol for a large external validation cohort study, which he hopes to launch in 2017.
Roche funded aspects of the ORBIT trial and the genetic substudy. Dr. Porter has been a consultant for Roche, as well as for AbbVie and Pfizer.
msullivan@frontlinemedcom.comOn Twitter @alz_gal
WASHINGTON – Three gene expression markers appear to predict response to some of the most common and powerful rheumatoid arthritis drugs employed in clinical practice.
In the largest gene-expression study of these drugs to date, researchers from Glasgow found 23 genes that predicted response to TNF inhibitors, and 23 more that predicted response to rituximab. They also found eight genes that predicted positive response to both types of drugs.
Just as important, the team found that 10% of patients in the study had none of the markers, Duncan Porter, MD, said during a press briefing at the annual meeting of the American College of Rheumatology.
If confirmed in independent validation cohorts, the findings could revolutionize medical therapy for rheumatoid arthritis, Dr. Porter said in an interview.
“Right now, the choice of treatment is mostly a flip of the coin,” said Dr. Porter, a rheumatologist at Queen Elizabeth University Hospital in Glasgow. “We don’t have a lot of comparative data to support one drug over the other, and most head-to-head studies show noninferiority.
“So, it would be ideal to be able to identify patients who will respond to one class or the other, and give them the right medicine the first time,” he noted. “If we can do that, we have the beginnings of really meaningful personalized therapy in RA.”
Dr. Porter reported a transcriptome-wide association study of 250 patients with RA who were enrolled in the ORBIT trial (Lancet. 2016 Jul 16;388[10041]:239-47). Dr. Porter was the study’s primary investigator.
ORBIT comprised 295 patients with active, seropositive rheumatoid arthritis who had failed disease-modifying antirheumatic therapy. They were randomized to B-cell depletion with rituximab or to the TNF inhibitors adalimumab or etanercept. ORBIT concluded that clinical response was similar with all three drugs. However, while most patients did well on their assigned drug, no matter which class, 20% failed their initial assignment.
The genetic study examined RNA transcripts in whole blood samples among a subset of the ORBIT patients. Most of the samples (70%) were used to identify markers and created a prediction model; that was then verified in the remaining 30% of samples. Markers were correlated to clinical response associated with rituximab and TNF inhibition. Clinical response was defined as a 1.2-point decline in the Disease Activity Score from baseline to 3 months of therapy.
At least 1 of the 54 genetic response markers was present in 90% of the population; 50% would have responded well to either drug, or 40% to just one of them.
But 10% of the population lacked either of the response markers – a very important finding, Dr. Porter noted, because if identified early, these patients could potentially avoid ineffective medication trials.
The markers’ predictive values were uniformly high, with a sensitivity of 93% and specificity of 91%. The positive predictive value was 96%, and the negative predictive value was 86%. Patients predicted to respond at 3 months were also more likely to have a good response (43% vs. 23%) or remission (23% vs. 10%), as measured by the Disease Activity Score 28 at 12 months.
While Dr. Porter was excited about the findings, he eyed them cautiously.
“The landscape is littered with biomarkers that had great early promise but failed in later validation studies,” he said. “We must be very careful in interpreting this. However, the other response studies have been small, and have not compared two drugs. This study was large with robust results, so we are encouraged.”
Dr Porter is now designing the protocol for a large external validation cohort study, which he hopes to launch in 2017.
Roche funded aspects of the ORBIT trial and the genetic substudy. Dr. Porter has been a consultant for Roche, as well as for AbbVie and Pfizer.
msullivan@frontlinemedcom.comOn Twitter @alz_gal
WASHINGTON – Three gene expression markers appear to predict response to some of the most common and powerful rheumatoid arthritis drugs employed in clinical practice.
In the largest gene-expression study of these drugs to date, researchers from Glasgow found 23 genes that predicted response to TNF inhibitors, and 23 more that predicted response to rituximab. They also found eight genes that predicted positive response to both types of drugs.
Just as important, the team found that 10% of patients in the study had none of the markers, Duncan Porter, MD, said during a press briefing at the annual meeting of the American College of Rheumatology.
If confirmed in independent validation cohorts, the findings could revolutionize medical therapy for rheumatoid arthritis, Dr. Porter said in an interview.
“Right now, the choice of treatment is mostly a flip of the coin,” said Dr. Porter, a rheumatologist at Queen Elizabeth University Hospital in Glasgow. “We don’t have a lot of comparative data to support one drug over the other, and most head-to-head studies show noninferiority.
“So, it would be ideal to be able to identify patients who will respond to one class or the other, and give them the right medicine the first time,” he noted. “If we can do that, we have the beginnings of really meaningful personalized therapy in RA.”
Dr. Porter reported a transcriptome-wide association study of 250 patients with RA who were enrolled in the ORBIT trial (Lancet. 2016 Jul 16;388[10041]:239-47). Dr. Porter was the study’s primary investigator.
ORBIT comprised 295 patients with active, seropositive rheumatoid arthritis who had failed disease-modifying antirheumatic therapy. They were randomized to B-cell depletion with rituximab or to the TNF inhibitors adalimumab or etanercept. ORBIT concluded that clinical response was similar with all three drugs. However, while most patients did well on their assigned drug, no matter which class, 20% failed their initial assignment.
The genetic study examined RNA transcripts in whole blood samples among a subset of the ORBIT patients. Most of the samples (70%) were used to identify markers and created a prediction model; that was then verified in the remaining 30% of samples. Markers were correlated to clinical response associated with rituximab and TNF inhibition. Clinical response was defined as a 1.2-point decline in the Disease Activity Score from baseline to 3 months of therapy.
At least 1 of the 54 genetic response markers was present in 90% of the population; 50% would have responded well to either drug, or 40% to just one of them.
But 10% of the population lacked either of the response markers – a very important finding, Dr. Porter noted, because if identified early, these patients could potentially avoid ineffective medication trials.
The markers’ predictive values were uniformly high, with a sensitivity of 93% and specificity of 91%. The positive predictive value was 96%, and the negative predictive value was 86%. Patients predicted to respond at 3 months were also more likely to have a good response (43% vs. 23%) or remission (23% vs. 10%), as measured by the Disease Activity Score 28 at 12 months.
While Dr. Porter was excited about the findings, he eyed them cautiously.
“The landscape is littered with biomarkers that had great early promise but failed in later validation studies,” he said. “We must be very careful in interpreting this. However, the other response studies have been small, and have not compared two drugs. This study was large with robust results, so we are encouraged.”
Dr Porter is now designing the protocol for a large external validation cohort study, which he hopes to launch in 2017.
Roche funded aspects of the ORBIT trial and the genetic substudy. Dr. Porter has been a consultant for Roche, as well as for AbbVie and Pfizer.
msullivan@frontlinemedcom.comOn Twitter @alz_gal
Key clinical point:
Major finding: The markers’ sensitivity and specificity for clinical response exceeded 90%.
Data source: The genetic-association study comprised 250 patients.
Disclosures: Roche funded aspects of the ORBIT trial and the genetic substudy. Dr. Porter has been a consultant for Roche, as well as for AbbVie and Pfizer.