Nancy Walsh

LIVERPOOL, ENGLAND — Maternal exposure to sunlight in late pregnancy can have a beneficial influence on the offspring's bone mineral density in later life, Dr. Nicola J. Goodson said at the annual meeting of the British Society for Rheumatology.

“In the United Kingdom, the main dietary sources of vitamin D are fish and fortified margarine, but more than 90% of the vitamin is obtained by casual exposure to the sun, and because of the latitude the majority of the population is vitamin D deficient for much of the year,” said Dr. Goodson of University Hospital Aintree, University of Liverpool (England).

Birth records and dual-energy x-ray absorptiometry (DXA) scan results were examined for 15,042 women and 2,160 men from the Morecambe Bay catchment district. The mean age was 62 years.

At the latitude of this district, 54 degrees north, the months with adequate sunlight are May through September. Patients therefore were categorized as having infant sunlight exposure if their birth months were between March and September and they could be expected to have at least 1 month of exposure to ultraviolet B light in the first 3 months of life. They were classified as antenatal exposure if their birth months were between May and November and they had at least 1 neonatal month of exposure to sunlight, said Dr. Goodson.

Overall, 51% of patients had BMD in the normal range. As expected, women had lower mean T scores, at −1.7, than did men, at −0.91, she said.

Analysis of sunlight exposure in the first 3 months of life and normal BMD, after adjustment for age at the time of the DXA scan, found no significant association, with an odds ratio (OR) of 1.

In contrast, for those categorized as antenatal exposure, there was a modest association with normal bone mineral density in adulthood, with an OR of 1.16, Dr. Goodson said. Those patients who had antenatal sunlight exposure also were likely to have osteopenia or osteoporosis: Those who were osteopenic had a 12% reduced odds of antenatal exposure and those who were osteoporotic had a 19% reduced odds of antenatal exposure, she said.

These associations were only seen among women.

In a separate analysis for those whose DXA scans were done before age 50, there was no association of early life sunlight exposure in either men or women. However, in these younger patients there was a very strong association of early life, rather than antenatal, exposure with osteoporosis. “Those patients in the osteoporotic range had a 49% reduced odds of having a birth month that enabled antenatal exposure to UVB,” she said.

In summary, she said, adult BMD was associated with birth month in this unselected DXA cohort.

“Maternal vitamin D levels should be optimized, particularly during the third trimester, either by diet or by safe UV exposure,” Dr. Goodson said.

LIVERPOOL, ENGLAND — Maternal exposure to sunlight in late pregnancy can have a beneficial influence on the offspring's bone mineral density in later life, Dr. Nicola J. Goodson said at the annual meeting of the British Society for Rheumatology.

“In the United Kingdom, the main dietary sources of vitamin D are fish and fortified margarine, but more than 90% of the vitamin is obtained by casual exposure to the sun, and because of the latitude the majority of the population is vitamin D deficient for much of the year,” said Dr. Goodson of University Hospital Aintree, University of Liverpool (England).

Birth records and dual-energy x-ray absorptiometry (DXA) scan results were examined for 15,042 women and 2,160 men from the Morecambe Bay catchment district. The mean age was 62 years.

At the latitude of this district, 54 degrees north, the months with adequate sunlight are May through September. Patients therefore were categorized as having infant sunlight exposure if their birth months were between March and September and they could be expected to have at least 1 month of exposure to ultraviolet B light in the first 3 months of life. They were classified as antenatal exposure if their birth months were between May and November and they had at least 1 neonatal month of exposure to sunlight, said Dr. Goodson.

Overall, 51% of patients had BMD in the normal range. As expected, women had lower mean T scores, at −1.7, than did men, at −0.91, she said.

Analysis of sunlight exposure in the first 3 months of life and normal BMD, after adjustment for age at the time of the DXA scan, found no significant association, with an odds ratio (OR) of 1.

In contrast, for those categorized as antenatal exposure, there was a modest association with normal bone mineral density in adulthood, with an OR of 1.16, Dr. Goodson said. Those patients who had antenatal sunlight exposure also were likely to have osteopenia or osteoporosis: Those who were osteopenic had a 12% reduced odds of antenatal exposure and those who were osteoporotic had a 19% reduced odds of antenatal exposure, she said.

These associations were only seen among women.

In a separate analysis for those whose DXA scans were done before age 50, there was no association of early life sunlight exposure in either men or women. However, in these younger patients there was a very strong association of early life, rather than antenatal, exposure with osteoporosis. “Those patients in the osteoporotic range had a 49% reduced odds of having a birth month that enabled antenatal exposure to UVB,” she said.

In summary, she said, adult BMD was associated with birth month in this unselected DXA cohort.

“Maternal vitamin D levels should be optimized, particularly during the third trimester, either by diet or by safe UV exposure,” Dr. Goodson said.

LIVERPOOL, ENGLAND — Maternal exposure to sunlight in late pregnancy can have a beneficial influence on the offspring's bone mineral density in later life, Dr. Nicola J. Goodson said at the annual meeting of the British Society for Rheumatology.

“In the United Kingdom, the main dietary sources of vitamin D are fish and fortified margarine, but more than 90% of the vitamin is obtained by casual exposure to the sun, and because of the latitude the majority of the population is vitamin D deficient for much of the year,” said Dr. Goodson of University Hospital Aintree, University of Liverpool (England).

Birth records and dual-energy x-ray absorptiometry (DXA) scan results were examined for 15,042 women and 2,160 men from the Morecambe Bay catchment district. The mean age was 62 years.

At the latitude of this district, 54 degrees north, the months with adequate sunlight are May through September. Patients therefore were categorized as having infant sunlight exposure if their birth months were between March and September and they could be expected to have at least 1 month of exposure to ultraviolet B light in the first 3 months of life. They were classified as antenatal exposure if their birth months were between May and November and they had at least 1 neonatal month of exposure to sunlight, said Dr. Goodson.

Overall, 51% of patients had BMD in the normal range. As expected, women had lower mean T scores, at −1.7, than did men, at −0.91, she said.

Analysis of sunlight exposure in the first 3 months of life and normal BMD, after adjustment for age at the time of the DXA scan, found no significant association, with an odds ratio (OR) of 1.

In contrast, for those categorized as antenatal exposure, there was a modest association with normal bone mineral density in adulthood, with an OR of 1.16, Dr. Goodson said. Those patients who had antenatal sunlight exposure also were likely to have osteopenia or osteoporosis: Those who were osteopenic had a 12% reduced odds of antenatal exposure and those who were osteoporotic had a 19% reduced odds of antenatal exposure, she said.

These associations were only seen among women.

In a separate analysis for those whose DXA scans were done before age 50, there was no association of early life sunlight exposure in either men or women. However, in these younger patients there was a very strong association of early life, rather than antenatal, exposure with osteoporosis. “Those patients in the osteoporotic range had a 49% reduced odds of having a birth month that enabled antenatal exposure to UVB,” she said.

In summary, she said, adult BMD was associated with birth month in this unselected DXA cohort.

“Maternal vitamin D levels should be optimized, particularly during the third trimester, either by diet or by safe UV exposure,” Dr. Goodson said.

NEW YORK — The contemporary use of minocycline for acne and hydralazine for heart failure is expanding the spectrum of drug-induced lupus.

Minocycline-induced lupus was first reported in the early 1990s, and more than 250 cases have now been reported to the World Health Organization. There is a 5:1 female-to-male predominance. Clinical features include fever, morning stiffness, myalgias, polyarthralgias, and symmetric arthritis. It is also characterized by large vessel vasculitis, and in more than 60% of patients, antineutrophil cytoplasmic antibodies are present and antihistone antibodies are not. This is in contrast to “classic” drug-induced lupus, in which antihistone antibodies are prominent.

Other autoantibodies also can be seen in minocycline-induced lupus, including antinuclear antibody (ANA) and anti-double-stranded DNA, said Dr. Andrew G. Franks Jr.

“The likelihood of developing a lupuslike syndrome is elevated 8.5-fold with minocycline, so many clinicians are now moving away from using minocycline for acne and rosacea and switching to doxycycline,” said Dr. Franks of the department of dermatology at New York University Medical Center, New York.

Hydralazine, which had fallen out of favor as an antihypertensive, has regained popularity as part of combination therapy for heart failure in African Americans following the benefits seen in the African-American Heart Failure Trial (N. Engl. J. Med. 2004;351:2049-57).

Hydralazine is one of the “big five” causes of classic drug-induced lupus, along with procainamide, isoniazid, quinidine, and phenytoin, but more than 100 drugs have been implicated in the 15,000–20,000 cases reported in the United States annually, he said.

“In my opinion, patients starting hydralazine, or any drug in the big five for that matter, should have a baseline test for ANA, although that is somewhat controversial,” Dr. Franks said.

The third main type of drug-induced lupus is subacute cutaneous lupus erythematosus (SCLE), which also is associated with an ever-widening variety of agents, including the thiazide diuretics, antifungals, calcium channel blockers, and ACE inhibitors. There also have been reports involving statins, leflunomide, and tumor necrosis factor inhibitors.

SCLE can be difficult to sort out, with targetoid lesions mixed with papulosquamous or annular lesions. Presentation can also resemble erythema multiforme or toxic epidermal necrolysis, with disadhesion of the epidermal layer and sloughing of the skin. “Patients with this subtype have very high morbidity and mortality,” he said.

An audience member asked what happens when the offending drug is withdrawn. “It can sometimes take months for this to remit, and some patients require additional therapy, but 95% of patients ultimately do remit,” Dr. Franks said at a rheumatology meeting sponsored by New York University.

Another audience member asked what to do if a patient's baseline ANA is positive, and whether that represents a contraindication to hydralazine therapy, for example. “That is why I said doing a baseline ANA is controversial,” Dr. Franks replied. “A number of groups do not suggest doing this, but clearly autoantibodies and a loss of tolerance precede the development of lupus, so one could be prudent and repeat the ANA yearly and see if it turns positive and the titer starts rising,” he said.

Dr. Franks reported having no financial relationships to disclose.

NEW YORK — The contemporary use of minocycline for acne and hydralazine for heart failure is expanding the spectrum of drug-induced lupus.

Minocycline-induced lupus was first reported in the early 1990s, and more than 250 cases have now been reported to the World Health Organization. There is a 5:1 female-to-male predominance. Clinical features include fever, morning stiffness, myalgias, polyarthralgias, and symmetric arthritis. It is also characterized by large vessel vasculitis, and in more than 60% of patients, antineutrophil cytoplasmic antibodies are present and antihistone antibodies are not. This is in contrast to “classic” drug-induced lupus, in which antihistone antibodies are prominent.

Other autoantibodies also can be seen in minocycline-induced lupus, including antinuclear antibody (ANA) and anti-double-stranded DNA, said Dr. Andrew G. Franks Jr.

“The likelihood of developing a lupuslike syndrome is elevated 8.5-fold with minocycline, so many clinicians are now moving away from using minocycline for acne and rosacea and switching to doxycycline,” said Dr. Franks of the department of dermatology at New York University Medical Center, New York.

Hydralazine, which had fallen out of favor as an antihypertensive, has regained popularity as part of combination therapy for heart failure in African Americans following the benefits seen in the African-American Heart Failure Trial (N. Engl. J. Med. 2004;351:2049-57).

Hydralazine is one of the “big five” causes of classic drug-induced lupus, along with procainamide, isoniazid, quinidine, and phenytoin, but more than 100 drugs have been implicated in the 15,000–20,000 cases reported in the United States annually, he said.

“In my opinion, patients starting hydralazine, or any drug in the big five for that matter, should have a baseline test for ANA, although that is somewhat controversial,” Dr. Franks said.

The third main type of drug-induced lupus is subacute cutaneous lupus erythematosus (SCLE), which also is associated with an ever-widening variety of agents, including the thiazide diuretics, antifungals, calcium channel blockers, and ACE inhibitors. There also have been reports involving statins, leflunomide, and tumor necrosis factor inhibitors.

SCLE can be difficult to sort out, with targetoid lesions mixed with papulosquamous or annular lesions. Presentation can also resemble erythema multiforme or toxic epidermal necrolysis, with disadhesion of the epidermal layer and sloughing of the skin. “Patients with this subtype have very high morbidity and mortality,” he said.

An audience member asked what happens when the offending drug is withdrawn. “It can sometimes take months for this to remit, and some patients require additional therapy, but 95% of patients ultimately do remit,” Dr. Franks said at a rheumatology meeting sponsored by New York University.

Another audience member asked what to do if a patient's baseline ANA is positive, and whether that represents a contraindication to hydralazine therapy, for example. “That is why I said doing a baseline ANA is controversial,” Dr. Franks replied. “A number of groups do not suggest doing this, but clearly autoantibodies and a loss of tolerance precede the development of lupus, so one could be prudent and repeat the ANA yearly and see if it turns positive and the titer starts rising,” he said.

Dr. Franks reported having no financial relationships to disclose.

NEW YORK — The contemporary use of minocycline for acne and hydralazine for heart failure is expanding the spectrum of drug-induced lupus.

Minocycline-induced lupus was first reported in the early 1990s, and more than 250 cases have now been reported to the World Health Organization. There is a 5:1 female-to-male predominance. Clinical features include fever, morning stiffness, myalgias, polyarthralgias, and symmetric arthritis. It is also characterized by large vessel vasculitis, and in more than 60% of patients, antineutrophil cytoplasmic antibodies are present and antihistone antibodies are not. This is in contrast to “classic” drug-induced lupus, in which antihistone antibodies are prominent.

Other autoantibodies also can be seen in minocycline-induced lupus, including antinuclear antibody (ANA) and anti-double-stranded DNA, said Dr. Andrew G. Franks Jr.

“The likelihood of developing a lupuslike syndrome is elevated 8.5-fold with minocycline, so many clinicians are now moving away from using minocycline for acne and rosacea and switching to doxycycline,” said Dr. Franks of the department of dermatology at New York University Medical Center, New York.

Hydralazine, which had fallen out of favor as an antihypertensive, has regained popularity as part of combination therapy for heart failure in African Americans following the benefits seen in the African-American Heart Failure Trial (N. Engl. J. Med. 2004;351:2049-57).

Hydralazine is one of the “big five” causes of classic drug-induced lupus, along with procainamide, isoniazid, quinidine, and phenytoin, but more than 100 drugs have been implicated in the 15,000–20,000 cases reported in the United States annually, he said.

“In my opinion, patients starting hydralazine, or any drug in the big five for that matter, should have a baseline test for ANA, although that is somewhat controversial,” Dr. Franks said.

The third main type of drug-induced lupus is subacute cutaneous lupus erythematosus (SCLE), which also is associated with an ever-widening variety of agents, including the thiazide diuretics, antifungals, calcium channel blockers, and ACE inhibitors. There also have been reports involving statins, leflunomide, and tumor necrosis factor inhibitors.

SCLE can be difficult to sort out, with targetoid lesions mixed with papulosquamous or annular lesions. Presentation can also resemble erythema multiforme or toxic epidermal necrolysis, with disadhesion of the epidermal layer and sloughing of the skin. “Patients with this subtype have very high morbidity and mortality,” he said.

An audience member asked what happens when the offending drug is withdrawn. “It can sometimes take months for this to remit, and some patients require additional therapy, but 95% of patients ultimately do remit,” Dr. Franks said at a rheumatology meeting sponsored by New York University.

Another audience member asked what to do if a patient's baseline ANA is positive, and whether that represents a contraindication to hydralazine therapy, for example. “That is why I said doing a baseline ANA is controversial,” Dr. Franks replied. “A number of groups do not suggest doing this, but clearly autoantibodies and a loss of tolerance precede the development of lupus, so one could be prudent and repeat the ANA yearly and see if it turns positive and the titer starts rising,” he said.

Dr. Franks reported having no financial relationships to disclose.

LIVERPOOL, ENGLAND — Giant cell arteritis is a critical ischemic process and should be considered a preventable stroke in the eye, yet vision loss almost always occurs before treatment is begun, according to Dr. Bhaskar Dasgupta.

Giant cell arteritis (GCA), the most common of the vasculitides, has an incidence of 7–29/100,000 people aged 50 and older in Europe, notably among women. The mean age of onset is 70 years.

GCA predominantly affects the cranial branches of arteries arising from the arch of the aorta, and often coexists with polymyalgia rheumatica (a generalized stiffness and aching of the muscles around the neck and shoulders), said Dr. Dasgupta, who headed a working group of the British Society for Rheumatology that has drafted guidelines for the management of GCA.

While new onset headache and elevated inflammatory markers are typical, GCA does not always present classically—particularly in patients at highest risk for neuro-ophthalmic complications.

“Pitfalls for the unwary include the fact that GCA does not always present with headache, and we now know that jaw claudication is a cardinal red flag warning of imminent vision loss,” Dr. Dasgupta said at the annual meeting of the British Society for Rheumatology.

Immediate institution of high-dose corticosteroids is needed to avoid loss of vision. Biopsy of the temporal artery also should be done, but treatment should not be delayed in the interim.

American College of Rheumatology criteria for GCA include age of onset 50 years or more, new onset headache, temporal artery abnormalities, elevated erythrocyte sedimentation rate, and abnormal artery biopsy. But other features—jaw and tongue claudication, diplopia, and amaurosis fugax—should be considered the “TIAs” of critical ischemia, said Dr. Dasgupta, a consultant rheumatologist at Southend University Hospital, Westcliff (England).

“The concept of symptom-to-thrombolysis time in myocardial infarct and stroke is well established. We believed that 'symptom-to-steroid' time should be adopted as an audit standard in GCA,” Dr. Dasgupta said in an interview.

Histologic findings on biopsy of the temporal artery can include mononuclear cell infiltration; granulomatous inflammation, usually with multinucleated giant cells, intimal proliferation, and vascular occlusion. The biopsy should preferably be done within a week of starting steroid therapy, but may remain positive for 14–28 days after treatment is initiated. A trial of corticosteroids should not substitute for the biopsy, Dr. Dasgupta said.

The usual starting dose of prednisone 40–60 mg/day should be continued until symptoms and laboratory abnormalities resolve. However, in the setting of evolving vision loss or amaurosis fugax, intravenous methylprednisolone, 500 mg to 1 g daily for 3 days followed by oral prednisone, should be used.

The steroids should not be tapered too quickly—certainly not before 4 weeks, Dr. Dasgupta cautioned. But because GCA tends to follow a chronic relapsing course and long-term corticosteroid therapy in these patients is associated with a high rate of adverse events—in one series nearly half of patients had fractures—various immunosuppressive therapies have been tried. Though methotrexate trials have had conflicting results, the drug was shown in a meta-analysis to have a small effect in preventing relapses, he said. There have also been promising case reports of biologics.

“In my view the timing of treatment is the most important factor. Our approach to GCA today is almost leisurely compared to the modern approach to critical ischemia at other sites such as the myocardium and the brain,” Dr. Dasgupta said.

At left: optic neuritis associated with GCA, characterized by a pale disc with diffuse edema, splinter shaped hemorrhages, and optic atrophy. Center: an example of central retinal artery occlusion in GCA. At right: a histology of giant cell arteritis. Photos courtesy Dr. Bhaskar Dasgupta

Jaw Claudication: An Important Sign

Dr. Dasgupta also presented a poster at the meeting of the case of an 81-year-old woman with a 3-day history of complete vision loss in the right eye and 2 weeks of intermittent blurred vision in the left eye.

She had been seen by her general practitioner 4 weeks earlier with jaw claudication but had no history of headache, scalp tenderness, or polymyalgia rheumatica. She was not referred for exclusion of giant cell arteritis (GCA) or given corticosteroids.

At Southend Hospital, she was unable to perceive light in her right eye and had minimal vision in the left. The right optic disc was swollen and pale and the retinal arteries were attenuated, while there was pallor and blurring of nasal margin of the left optic disc. Both temporal arteries were thickened, wrote Dr. Frances A. Borg, Dr. Dasgupta's colleague. Erythrocyte sedimentation rate was 27 mm/hr and C-reactive protein (CRP) was 13 mg/L. Temporal artery biopsy confirmed GCA, revealing severe mediointimal proliferation.

She was treated with IV methylprednisolone for 3 days, with vision improvement in the left eye and a fall in CRP to 2 mg/L, but when she was switched to oral prednisone the left-sided vision again deteriorated. Her vision is currently 20/200 in the left eye, and she cannot perceive light in her right.

“This case illustrates the importance of recognizing jaw claudication as a predictor of vision loss in GCA. This patient had none of the other well-recognized features of GCA, and only a modest rise in her inflammatory markers. We suspect that if she had described headache, the diagnosis would have been recognized when she initially presented, and steroid therapy would have been instituted in time to save her vision,” Dr. Borg wrote.

LIVERPOOL, ENGLAND — Giant cell arteritis is a critical ischemic process and should be considered a preventable stroke in the eye, yet vision loss almost always occurs before treatment is begun, according to Dr. Bhaskar Dasgupta.

Giant cell arteritis (GCA), the most common of the vasculitides, has an incidence of 7–29/100,000 people aged 50 and older in Europe, notably among women. The mean age of onset is 70 years.

GCA predominantly affects the cranial branches of arteries arising from the arch of the aorta, and often coexists with polymyalgia rheumatica (a generalized stiffness and aching of the muscles around the neck and shoulders), said Dr. Dasgupta, who headed a working group of the British Society for Rheumatology that has drafted guidelines for the management of GCA.

While new onset headache and elevated inflammatory markers are typical, GCA does not always present classically—particularly in patients at highest risk for neuro-ophthalmic complications.

“Pitfalls for the unwary include the fact that GCA does not always present with headache, and we now know that jaw claudication is a cardinal red flag warning of imminent vision loss,” Dr. Dasgupta said at the annual meeting of the British Society for Rheumatology.

Immediate institution of high-dose corticosteroids is needed to avoid loss of vision. Biopsy of the temporal artery also should be done, but treatment should not be delayed in the interim.

American College of Rheumatology criteria for GCA include age of onset 50 years or more, new onset headache, temporal artery abnormalities, elevated erythrocyte sedimentation rate, and abnormal artery biopsy. But other features—jaw and tongue claudication, diplopia, and amaurosis fugax—should be considered the “TIAs” of critical ischemia, said Dr. Dasgupta, a consultant rheumatologist at Southend University Hospital, Westcliff (England).

“The concept of symptom-to-thrombolysis time in myocardial infarct and stroke is well established. We believed that 'symptom-to-steroid' time should be adopted as an audit standard in GCA,” Dr. Dasgupta said in an interview.

Histologic findings on biopsy of the temporal artery can include mononuclear cell infiltration; granulomatous inflammation, usually with multinucleated giant cells, intimal proliferation, and vascular occlusion. The biopsy should preferably be done within a week of starting steroid therapy, but may remain positive for 14–28 days after treatment is initiated. A trial of corticosteroids should not substitute for the biopsy, Dr. Dasgupta said.

The usual starting dose of prednisone 40–60 mg/day should be continued until symptoms and laboratory abnormalities resolve. However, in the setting of evolving vision loss or amaurosis fugax, intravenous methylprednisolone, 500 mg to 1 g daily for 3 days followed by oral prednisone, should be used.

The steroids should not be tapered too quickly—certainly not before 4 weeks, Dr. Dasgupta cautioned. But because GCA tends to follow a chronic relapsing course and long-term corticosteroid therapy in these patients is associated with a high rate of adverse events—in one series nearly half of patients had fractures—various immunosuppressive therapies have been tried. Though methotrexate trials have had conflicting results, the drug was shown in a meta-analysis to have a small effect in preventing relapses, he said. There have also been promising case reports of biologics.

“In my view the timing of treatment is the most important factor. Our approach to GCA today is almost leisurely compared to the modern approach to critical ischemia at other sites such as the myocardium and the brain,” Dr. Dasgupta said.

At left: optic neuritis associated with GCA, characterized by a pale disc with diffuse edema, splinter shaped hemorrhages, and optic atrophy. Center: an example of central retinal artery occlusion in GCA. At right: a histology of giant cell arteritis. Photos courtesy Dr. Bhaskar Dasgupta

Jaw Claudication: An Important Sign

Dr. Dasgupta also presented a poster at the meeting of the case of an 81-year-old woman with a 3-day history of complete vision loss in the right eye and 2 weeks of intermittent blurred vision in the left eye.

She had been seen by her general practitioner 4 weeks earlier with jaw claudication but had no history of headache, scalp tenderness, or polymyalgia rheumatica. She was not referred for exclusion of giant cell arteritis (GCA) or given corticosteroids.

At Southend Hospital, she was unable to perceive light in her right eye and had minimal vision in the left. The right optic disc was swollen and pale and the retinal arteries were attenuated, while there was pallor and blurring of nasal margin of the left optic disc. Both temporal arteries were thickened, wrote Dr. Frances A. Borg, Dr. Dasgupta's colleague. Erythrocyte sedimentation rate was 27 mm/hr and C-reactive protein (CRP) was 13 mg/L. Temporal artery biopsy confirmed GCA, revealing severe mediointimal proliferation.

She was treated with IV methylprednisolone for 3 days, with vision improvement in the left eye and a fall in CRP to 2 mg/L, but when she was switched to oral prednisone the left-sided vision again deteriorated. Her vision is currently 20/200 in the left eye, and she cannot perceive light in her right.

“This case illustrates the importance of recognizing jaw claudication as a predictor of vision loss in GCA. This patient had none of the other well-recognized features of GCA, and only a modest rise in her inflammatory markers. We suspect that if she had described headache, the diagnosis would have been recognized when she initially presented, and steroid therapy would have been instituted in time to save her vision,” Dr. Borg wrote.

LIVERPOOL, ENGLAND — Giant cell arteritis is a critical ischemic process and should be considered a preventable stroke in the eye, yet vision loss almost always occurs before treatment is begun, according to Dr. Bhaskar Dasgupta.

Giant cell arteritis (GCA), the most common of the vasculitides, has an incidence of 7–29/100,000 people aged 50 and older in Europe, notably among women. The mean age of onset is 70 years.

GCA predominantly affects the cranial branches of arteries arising from the arch of the aorta, and often coexists with polymyalgia rheumatica (a generalized stiffness and aching of the muscles around the neck and shoulders), said Dr. Dasgupta, who headed a working group of the British Society for Rheumatology that has drafted guidelines for the management of GCA.

While new onset headache and elevated inflammatory markers are typical, GCA does not always present classically—particularly in patients at highest risk for neuro-ophthalmic complications.

“Pitfalls for the unwary include the fact that GCA does not always present with headache, and we now know that jaw claudication is a cardinal red flag warning of imminent vision loss,” Dr. Dasgupta said at the annual meeting of the British Society for Rheumatology.

Immediate institution of high-dose corticosteroids is needed to avoid loss of vision. Biopsy of the temporal artery also should be done, but treatment should not be delayed in the interim.

American College of Rheumatology criteria for GCA include age of onset 50 years or more, new onset headache, temporal artery abnormalities, elevated erythrocyte sedimentation rate, and abnormal artery biopsy. But other features—jaw and tongue claudication, diplopia, and amaurosis fugax—should be considered the “TIAs” of critical ischemia, said Dr. Dasgupta, a consultant rheumatologist at Southend University Hospital, Westcliff (England).

“The concept of symptom-to-thrombolysis time in myocardial infarct and stroke is well established. We believed that 'symptom-to-steroid' time should be adopted as an audit standard in GCA,” Dr. Dasgupta said in an interview.

Histologic findings on biopsy of the temporal artery can include mononuclear cell infiltration; granulomatous inflammation, usually with multinucleated giant cells, intimal proliferation, and vascular occlusion. The biopsy should preferably be done within a week of starting steroid therapy, but may remain positive for 14–28 days after treatment is initiated. A trial of corticosteroids should not substitute for the biopsy, Dr. Dasgupta said.

The usual starting dose of prednisone 40–60 mg/day should be continued until symptoms and laboratory abnormalities resolve. However, in the setting of evolving vision loss or amaurosis fugax, intravenous methylprednisolone, 500 mg to 1 g daily for 3 days followed by oral prednisone, should be used.

The steroids should not be tapered too quickly—certainly not before 4 weeks, Dr. Dasgupta cautioned. But because GCA tends to follow a chronic relapsing course and long-term corticosteroid therapy in these patients is associated with a high rate of adverse events—in one series nearly half of patients had fractures—various immunosuppressive therapies have been tried. Though methotrexate trials have had conflicting results, the drug was shown in a meta-analysis to have a small effect in preventing relapses, he said. There have also been promising case reports of biologics.

“In my view the timing of treatment is the most important factor. Our approach to GCA today is almost leisurely compared to the modern approach to critical ischemia at other sites such as the myocardium and the brain,” Dr. Dasgupta said.

At left: optic neuritis associated with GCA, characterized by a pale disc with diffuse edema, splinter shaped hemorrhages, and optic atrophy. Center: an example of central retinal artery occlusion in GCA. At right: a histology of giant cell arteritis. Photos courtesy Dr. Bhaskar Dasgupta

Jaw Claudication: An Important Sign

Dr. Dasgupta also presented a poster at the meeting of the case of an 81-year-old woman with a 3-day history of complete vision loss in the right eye and 2 weeks of intermittent blurred vision in the left eye.

She had been seen by her general practitioner 4 weeks earlier with jaw claudication but had no history of headache, scalp tenderness, or polymyalgia rheumatica. She was not referred for exclusion of giant cell arteritis (GCA) or given corticosteroids.

At Southend Hospital, she was unable to perceive light in her right eye and had minimal vision in the left. The right optic disc was swollen and pale and the retinal arteries were attenuated, while there was pallor and blurring of nasal margin of the left optic disc. Both temporal arteries were thickened, wrote Dr. Frances A. Borg, Dr. Dasgupta's colleague. Erythrocyte sedimentation rate was 27 mm/hr and C-reactive protein (CRP) was 13 mg/L. Temporal artery biopsy confirmed GCA, revealing severe mediointimal proliferation.

She was treated with IV methylprednisolone for 3 days, with vision improvement in the left eye and a fall in CRP to 2 mg/L, but when she was switched to oral prednisone the left-sided vision again deteriorated. Her vision is currently 20/200 in the left eye, and she cannot perceive light in her right.

“This case illustrates the importance of recognizing jaw claudication as a predictor of vision loss in GCA. This patient had none of the other well-recognized features of GCA, and only a modest rise in her inflammatory markers. We suspect that if she had described headache, the diagnosis would have been recognized when she initially presented, and steroid therapy would have been instituted in time to save her vision,” Dr. Borg wrote.

LIVERPOOL, ENGLAND — Patients with rheumatoid arthritis who have a history of cigarette smoking are more likely to have a poor response to anti-tumor necrosis factor therapy than are those who have never smoked.

Recent studies have provided strong evidence that cigarette smoking is a risk factor in susceptibility to rheumatoid arthritis (RA) and more severe disease. Smokers with RA appear to have increased production of cytokines like tumor necrosis factor, and autoantibodies such as rheumatoid factor. A recent study from the British Society for Rheumatology's biologics register found current smokers had a low response rate to infliximab (Rheumatology [Oxford] 2006;45:1558-65).

“To see if smoking affects the response to therapy in our patients and to determine if there is a relationship between response and pack-year history, we collected demographic data and smoking histories for all patients at our hospital who were started on anti-TNF drugs since 2002,” said Dr. Derek L. Mattey of Staffordshire Rheumatology Centre, University Hospital of North Staffordshire, Stoke-on-Trent (England). A total of 154 patients whose mean age was 65 years were included. Infliximab was the agent used by 83 patients, etanercept by 55, and adalimumab by 16.

Two-thirds of the patients reported ever having smoked, but only 25% were still current smokers at the time they initiated treatment.

The extent of previous smoking was quantified, with one pack-year being equivalent to 20 cigarettes per day for 1 year, and intensity of smoking stratified as never (0 pack-years), light (1–15 pack-years), moderate (16–30 pack-years), and heavy (more than 30 pack-years).

At baseline, smokers were more likely to be rheumatoid factor positive and have nodular disease, but smokers and nonsmokers did not differ in baseline Disease Activity Score (DAS) 28, Health Assessment Questionnaire (HAQ) scores, pain scores, or C-reactive protein level, Dr. Mattey said.

Response was defined according to the EULAR (European League AgainstRheumatism) improvement criteria, based on 3-month DAS28 and absolute change in DAS28 from baseline.

At 3 months, there were significant differences between the groups, with patients whose smoking history exceeded 30 pack-years having an odds ratio of 7.4 for nonresponse versus patients who never smoked. The odds ratios for those in the light and moderate groups were 1.9 and 1.8, respectively.

Multivariate logistic regression analysis showed that the association of pack-year history with nonresponse was independent of age, sex, disease duration, baseline DAS28, and HAQ scores.

Moreover, the association was independent of smoking status at initiation of anti-TNF treatment.

Analysis also determined that the association of smoking and nonresponse was significant at 3 months only for infliximab, but there also was a trend for nonresponse by 12 months for etanercept.

On the DAS28, the subjective areas of patient global assessment and tender joint count were associated with increased pack-year history, unlike the objective areas of erythrocyte sedimentation rate and swollen joint count. “There also was an inverse relationship between pack-years smoked and change in pain scores,” he said at the annual meeting of the British Society for Rheumatology.

Dr. Mattey also undertook an analysis of the cytokine and metalloproteinase profiles in a group of 80 patients with early RA, to identify the possible impact of smoking at this level. In a poster, they reported that on ELISA and multiplex analyses, elevated levels of interleukin-8, vascular endothelial growth factor, and metalloproteinases 1, 8, and 9 were associated with smoking, and vascular endothelial growth factor and metalloproteinases 8 and 9 showed significant associations with number of pack-years.

LIVERPOOL, ENGLAND — Patients with rheumatoid arthritis who have a history of cigarette smoking are more likely to have a poor response to anti-tumor necrosis factor therapy than are those who have never smoked.

Recent studies have provided strong evidence that cigarette smoking is a risk factor in susceptibility to rheumatoid arthritis (RA) and more severe disease. Smokers with RA appear to have increased production of cytokines like tumor necrosis factor, and autoantibodies such as rheumatoid factor. A recent study from the British Society for Rheumatology's biologics register found current smokers had a low response rate to infliximab (Rheumatology [Oxford] 2006;45:1558-65).

“To see if smoking affects the response to therapy in our patients and to determine if there is a relationship between response and pack-year history, we collected demographic data and smoking histories for all patients at our hospital who were started on anti-TNF drugs since 2002,” said Dr. Derek L. Mattey of Staffordshire Rheumatology Centre, University Hospital of North Staffordshire, Stoke-on-Trent (England). A total of 154 patients whose mean age was 65 years were included. Infliximab was the agent used by 83 patients, etanercept by 55, and adalimumab by 16.

Two-thirds of the patients reported ever having smoked, but only 25% were still current smokers at the time they initiated treatment.

The extent of previous smoking was quantified, with one pack-year being equivalent to 20 cigarettes per day for 1 year, and intensity of smoking stratified as never (0 pack-years), light (1–15 pack-years), moderate (16–30 pack-years), and heavy (more than 30 pack-years).

At baseline, smokers were more likely to be rheumatoid factor positive and have nodular disease, but smokers and nonsmokers did not differ in baseline Disease Activity Score (DAS) 28, Health Assessment Questionnaire (HAQ) scores, pain scores, or C-reactive protein level, Dr. Mattey said.

Response was defined according to the EULAR (European League AgainstRheumatism) improvement criteria, based on 3-month DAS28 and absolute change in DAS28 from baseline.

At 3 months, there were significant differences between the groups, with patients whose smoking history exceeded 30 pack-years having an odds ratio of 7.4 for nonresponse versus patients who never smoked. The odds ratios for those in the light and moderate groups were 1.9 and 1.8, respectively.

Multivariate logistic regression analysis showed that the association of pack-year history with nonresponse was independent of age, sex, disease duration, baseline DAS28, and HAQ scores.

Moreover, the association was independent of smoking status at initiation of anti-TNF treatment.

Analysis also determined that the association of smoking and nonresponse was significant at 3 months only for infliximab, but there also was a trend for nonresponse by 12 months for etanercept.

On the DAS28, the subjective areas of patient global assessment and tender joint count were associated with increased pack-year history, unlike the objective areas of erythrocyte sedimentation rate and swollen joint count. “There also was an inverse relationship between pack-years smoked and change in pain scores,” he said at the annual meeting of the British Society for Rheumatology.

Dr. Mattey also undertook an analysis of the cytokine and metalloproteinase profiles in a group of 80 patients with early RA, to identify the possible impact of smoking at this level. In a poster, they reported that on ELISA and multiplex analyses, elevated levels of interleukin-8, vascular endothelial growth factor, and metalloproteinases 1, 8, and 9 were associated with smoking, and vascular endothelial growth factor and metalloproteinases 8 and 9 showed significant associations with number of pack-years.

LIVERPOOL, ENGLAND — Patients with rheumatoid arthritis who have a history of cigarette smoking are more likely to have a poor response to anti-tumor necrosis factor therapy than are those who have never smoked.

Recent studies have provided strong evidence that cigarette smoking is a risk factor in susceptibility to rheumatoid arthritis (RA) and more severe disease. Smokers with RA appear to have increased production of cytokines like tumor necrosis factor, and autoantibodies such as rheumatoid factor. A recent study from the British Society for Rheumatology's biologics register found current smokers had a low response rate to infliximab (Rheumatology [Oxford] 2006;45:1558-65).

“To see if smoking affects the response to therapy in our patients and to determine if there is a relationship between response and pack-year history, we collected demographic data and smoking histories for all patients at our hospital who were started on anti-TNF drugs since 2002,” said Dr. Derek L. Mattey of Staffordshire Rheumatology Centre, University Hospital of North Staffordshire, Stoke-on-Trent (England). A total of 154 patients whose mean age was 65 years were included. Infliximab was the agent used by 83 patients, etanercept by 55, and adalimumab by 16.

Two-thirds of the patients reported ever having smoked, but only 25% were still current smokers at the time they initiated treatment.

The extent of previous smoking was quantified, with one pack-year being equivalent to 20 cigarettes per day for 1 year, and intensity of smoking stratified as never (0 pack-years), light (1–15 pack-years), moderate (16–30 pack-years), and heavy (more than 30 pack-years).

At baseline, smokers were more likely to be rheumatoid factor positive and have nodular disease, but smokers and nonsmokers did not differ in baseline Disease Activity Score (DAS) 28, Health Assessment Questionnaire (HAQ) scores, pain scores, or C-reactive protein level, Dr. Mattey said.

Response was defined according to the EULAR (European League AgainstRheumatism) improvement criteria, based on 3-month DAS28 and absolute change in DAS28 from baseline.

At 3 months, there were significant differences between the groups, with patients whose smoking history exceeded 30 pack-years having an odds ratio of 7.4 for nonresponse versus patients who never smoked. The odds ratios for those in the light and moderate groups were 1.9 and 1.8, respectively.

Multivariate logistic regression analysis showed that the association of pack-year history with nonresponse was independent of age, sex, disease duration, baseline DAS28, and HAQ scores.

Moreover, the association was independent of smoking status at initiation of anti-TNF treatment.

Analysis also determined that the association of smoking and nonresponse was significant at 3 months only for infliximab, but there also was a trend for nonresponse by 12 months for etanercept.

On the DAS28, the subjective areas of patient global assessment and tender joint count were associated with increased pack-year history, unlike the objective areas of erythrocyte sedimentation rate and swollen joint count. “There also was an inverse relationship between pack-years smoked and change in pain scores,” he said at the annual meeting of the British Society for Rheumatology.

Dr. Mattey also undertook an analysis of the cytokine and metalloproteinase profiles in a group of 80 patients with early RA, to identify the possible impact of smoking at this level. In a poster, they reported that on ELISA and multiplex analyses, elevated levels of interleukin-8, vascular endothelial growth factor, and metalloproteinases 1, 8, and 9 were associated with smoking, and vascular endothelial growth factor and metalloproteinases 8 and 9 showed significant associations with number of pack-years.

LIVERPOOL, ENGLAND — Rituximab has been used successfully in a real-world setting as a first-line biologic therapy for rheumatoid arthritis that does not respond to conventional disease-modifying drugs, Dr. Ai Lyn Tan reported at the annual meeting of the British Society for Rheumatology.

Rituximab is licensed in the United Kingdom for the treatment of adults with rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, conventional disease-modifying anti-rheumatic drugs (DMARDs) and to one or more tumor necrosis factor (TNF) inhibitors. In the United States it is licensed for use in combination with methotrexate for management of moderately to severely active RA that has not responded to treatment with one or more anti-TNF agents.

Licensure of the TNF inhibitors posed financial strains on the U.K. health care system, and the drugs were restricted in availability in some areas. Because of this lack of availability and the fact that rituximab had been shown to be effective in RA in trials of patients who had not previously received anti-TNF therapy, this drug has been used as a first-line biologic since 2004 by Dr. Tan and her colleagues at the University of Leeds (England) and Chapel Allerton Hospital, Leeds.

A total of 39 patients who had failed at least one DMARD have received two initial infusions of rituximab 2 weeks apart. In 17 patients the doses were 1,000 mg each, and in 22 the doses were 500 mg each.

Two-thirds of the patients were women. Their median age was 58 years and median disease duration was 7 years. Thirty of the patients were rheumatoid factor (RF) positive at baseline, and 16 were also antinuclear antibody (ANA) positive.

Clinical outcome data were available for 37 patients and safety data for all 39.

Clinical assessments using the Disease Activity Score (DAS)28 and EULAR response criteria were done at 3, 6, 9, and 12 months. The EULAR response criteria use the change in DAS and the level of DAS achieved to classify patients as good, moderate, or nonresponders.

At all time points, there was a significant improvement in DAS28. EULAR good responses were seen in 40% of patients at 3 months and in 50% of patients at 12 months, while overall EULAR responses were seen in 88% and 77%, respectively, at those time points.

By 6 months ANA became negative in 40% of patients in whom it had been positive at baseline, and in 88% of RF-positive patients the antibody level had fallen. Four of the previously RF-positive patients became seronegative by 6 months, and these reductions were sustained at 12 months, Dr. Tan wrote in a poster presented at the meeting.

Slightly better responses were seen in patients who received the higher dose, with 82% in the 500-mg group and 94% of those in the 1,000-mg group achieving EULAR responses. Nonetheless, she suggested that it might be “prudent” to start on lower doses since treatment is likely to be needed long term.

Thus far 25 patients have been retreated, at a median of 13 months after the initial infusions, and 7 have received a third treatment, at a median of 11 months after the second treatment.

Two patients were switched to anti-TNF therapy following early treatment failure and a third was switched following an allergic reaction to the second infusion of rituximab, according to Dr. Tan, who declared no conflicts of interest.

One 67-year-old patient with preexisting lung disease died 3 months after treatment from presumed bilateral bronchopneumonia and possible methotrexate pneumonitis, and a second 61-year-old man died of a myocardial infarction while awaiting coronary angiography for angina pectoris. This outcome was not considered to be related to therapy.

In an interview, Dr. Tan said that her study showed that rituximab is effective as first-line therapy in patients with severe RA. “This is important because it can be used in patients in whom the TNF blockers are contraindicated,” she said.

Almost half of the patients in this study had disease features that could have caused concerns with TNF blockade, such as risks of infection and strong ANA positivity (Rheumatology 2008:47;865-7).

“I think this will be an important role for rituximab in RA,” Dr. Tan said.

LIVERPOOL, ENGLAND — Rituximab has been used successfully in a real-world setting as a first-line biologic therapy for rheumatoid arthritis that does not respond to conventional disease-modifying drugs, Dr. Ai Lyn Tan reported at the annual meeting of the British Society for Rheumatology.

Rituximab is licensed in the United Kingdom for the treatment of adults with rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, conventional disease-modifying anti-rheumatic drugs (DMARDs) and to one or more tumor necrosis factor (TNF) inhibitors. In the United States it is licensed for use in combination with methotrexate for management of moderately to severely active RA that has not responded to treatment with one or more anti-TNF agents.

Licensure of the TNF inhibitors posed financial strains on the U.K. health care system, and the drugs were restricted in availability in some areas. Because of this lack of availability and the fact that rituximab had been shown to be effective in RA in trials of patients who had not previously received anti-TNF therapy, this drug has been used as a first-line biologic since 2004 by Dr. Tan and her colleagues at the University of Leeds (England) and Chapel Allerton Hospital, Leeds.

A total of 39 patients who had failed at least one DMARD have received two initial infusions of rituximab 2 weeks apart. In 17 patients the doses were 1,000 mg each, and in 22 the doses were 500 mg each.

Two-thirds of the patients were women. Their median age was 58 years and median disease duration was 7 years. Thirty of the patients were rheumatoid factor (RF) positive at baseline, and 16 were also antinuclear antibody (ANA) positive.

Clinical outcome data were available for 37 patients and safety data for all 39.

Clinical assessments using the Disease Activity Score (DAS)28 and EULAR response criteria were done at 3, 6, 9, and 12 months. The EULAR response criteria use the change in DAS and the level of DAS achieved to classify patients as good, moderate, or nonresponders.

At all time points, there was a significant improvement in DAS28. EULAR good responses were seen in 40% of patients at 3 months and in 50% of patients at 12 months, while overall EULAR responses were seen in 88% and 77%, respectively, at those time points.

By 6 months ANA became negative in 40% of patients in whom it had been positive at baseline, and in 88% of RF-positive patients the antibody level had fallen. Four of the previously RF-positive patients became seronegative by 6 months, and these reductions were sustained at 12 months, Dr. Tan wrote in a poster presented at the meeting.

Slightly better responses were seen in patients who received the higher dose, with 82% in the 500-mg group and 94% of those in the 1,000-mg group achieving EULAR responses. Nonetheless, she suggested that it might be “prudent” to start on lower doses since treatment is likely to be needed long term.

Thus far 25 patients have been retreated, at a median of 13 months after the initial infusions, and 7 have received a third treatment, at a median of 11 months after the second treatment.

Two patients were switched to anti-TNF therapy following early treatment failure and a third was switched following an allergic reaction to the second infusion of rituximab, according to Dr. Tan, who declared no conflicts of interest.

One 67-year-old patient with preexisting lung disease died 3 months after treatment from presumed bilateral bronchopneumonia and possible methotrexate pneumonitis, and a second 61-year-old man died of a myocardial infarction while awaiting coronary angiography for angina pectoris. This outcome was not considered to be related to therapy.

In an interview, Dr. Tan said that her study showed that rituximab is effective as first-line therapy in patients with severe RA. “This is important because it can be used in patients in whom the TNF blockers are contraindicated,” she said.

Almost half of the patients in this study had disease features that could have caused concerns with TNF blockade, such as risks of infection and strong ANA positivity (Rheumatology 2008:47;865-7).

“I think this will be an important role for rituximab in RA,” Dr. Tan said.

LIVERPOOL, ENGLAND — Rituximab has been used successfully in a real-world setting as a first-line biologic therapy for rheumatoid arthritis that does not respond to conventional disease-modifying drugs, Dr. Ai Lyn Tan reported at the annual meeting of the British Society for Rheumatology.

Rituximab is licensed in the United Kingdom for the treatment of adults with rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, conventional disease-modifying anti-rheumatic drugs (DMARDs) and to one or more tumor necrosis factor (TNF) inhibitors. In the United States it is licensed for use in combination with methotrexate for management of moderately to severely active RA that has not responded to treatment with one or more anti-TNF agents.

Licensure of the TNF inhibitors posed financial strains on the U.K. health care system, and the drugs were restricted in availability in some areas. Because of this lack of availability and the fact that rituximab had been shown to be effective in RA in trials of patients who had not previously received anti-TNF therapy, this drug has been used as a first-line biologic since 2004 by Dr. Tan and her colleagues at the University of Leeds (England) and Chapel Allerton Hospital, Leeds.

A total of 39 patients who had failed at least one DMARD have received two initial infusions of rituximab 2 weeks apart. In 17 patients the doses were 1,000 mg each, and in 22 the doses were 500 mg each.

Two-thirds of the patients were women. Their median age was 58 years and median disease duration was 7 years. Thirty of the patients were rheumatoid factor (RF) positive at baseline, and 16 were also antinuclear antibody (ANA) positive.

Clinical outcome data were available for 37 patients and safety data for all 39.

Clinical assessments using the Disease Activity Score (DAS)28 and EULAR response criteria were done at 3, 6, 9, and 12 months. The EULAR response criteria use the change in DAS and the level of DAS achieved to classify patients as good, moderate, or nonresponders.

At all time points, there was a significant improvement in DAS28. EULAR good responses were seen in 40% of patients at 3 months and in 50% of patients at 12 months, while overall EULAR responses were seen in 88% and 77%, respectively, at those time points.

By 6 months ANA became negative in 40% of patients in whom it had been positive at baseline, and in 88% of RF-positive patients the antibody level had fallen. Four of the previously RF-positive patients became seronegative by 6 months, and these reductions were sustained at 12 months, Dr. Tan wrote in a poster presented at the meeting.

Slightly better responses were seen in patients who received the higher dose, with 82% in the 500-mg group and 94% of those in the 1,000-mg group achieving EULAR responses. Nonetheless, she suggested that it might be “prudent” to start on lower doses since treatment is likely to be needed long term.

Thus far 25 patients have been retreated, at a median of 13 months after the initial infusions, and 7 have received a third treatment, at a median of 11 months after the second treatment.

Two patients were switched to anti-TNF therapy following early treatment failure and a third was switched following an allergic reaction to the second infusion of rituximab, according to Dr. Tan, who declared no conflicts of interest.

One 67-year-old patient with preexisting lung disease died 3 months after treatment from presumed bilateral bronchopneumonia and possible methotrexate pneumonitis, and a second 61-year-old man died of a myocardial infarction while awaiting coronary angiography for angina pectoris. This outcome was not considered to be related to therapy.

In an interview, Dr. Tan said that her study showed that rituximab is effective as first-line therapy in patients with severe RA. “This is important because it can be used in patients in whom the TNF blockers are contraindicated,” she said.

Almost half of the patients in this study had disease features that could have caused concerns with TNF blockade, such as risks of infection and strong ANA positivity (Rheumatology 2008:47;865-7).

“I think this will be an important role for rituximab in RA,” Dr. Tan said.

LIVERPOOL, ENGLAND — Serious and even fatal infections continue to occur in patients being treated with tumor necrosis factor-blocking agents and other biologics, emphasizing the need for heightened vigilance.

This was demonstrated in a series of posters presented at the annual meeting of the British Society for Rheumatology. In one case report, a 49-year-old woman with rheumatoid arthritis (RA) who had been treated unsuccessfully with methotrexate, sulfasalazine, leflunomide, and high doses of prednisone was started on etanercept. She developed lesions on her palms and soles typical of pustular psoriasis, and was then switched to infliximab, prednisone, and methotrexate. Following the third infusion she was hospitalized with fever and a widespread vesicular rash, according to Dr. Elizabeth A. Justice of University Hospital Birmingham (England).

The patient's C-reactive protein level was 153 mg/L, but the results of a sepsis screen and chest x-ray were normal. Fluid from the skin vesicles was found to contain herpes simplex virus type 1 (HSV-1).

The TNF blocker was stopped and acyclovir was given in dosages of 800 mg five times daily. The rash began to resolve within 48 hours, and after 2 weeks the acyclovir dosage was reduced to 400 mg twice daily.

Two months later she commenced adalimumab, 40 mg every other week, continuing on acyclovir prophylaxis in dosages of 200 mg every other day, with no recurrence of the HSV lesions.

“This is the first reported case of disseminated cutaneous HSV-1 infection following treatment with infliximab, an unusual adverse reaction we believe to be a direct result of her immunosuppressive therapy,” Dr. Justice wrote.

A second case involved a 49-year-old man with a 14-year history of seropositive nonerosive eosinophilic RA. He presented with shortness of breath but no cough, fever, or chest pain, said Dr. Deepak R. Jadon. The patient had been treated previously with etanercept and adalimumab with limited benefit, and 2 months earlier he had begun treatment with rituximab. He also had previously been on sulfasalazine for 13 years, but 2 months earlier switched to leflunomide, 10 mg/day, plus methotrexate, 15 mg/wk. He developed low-grade fever, tachycardia, dyspnea, and orthopnea, with end-inspiratory crackles audible bilaterally in the mid-lower chest. Arterial blood gases showed saturation of 75% and partial pressure of oxygen of 5.63 mm Hg. He also had neutrophilia and eosinopenia, and his C-reactive protein level was 174 mg/L.

A chest film showed patchy shadowing, and a CT scan revealed extensive ground glass parenchymal abnormalities affecting both mid and lower zones, according to Dr. Jadon of the department of rheumatology, Royal Berkshire Hospital, Reading (England).

Methotrexate and leflunomide were stopped, and calcium folinate (leucovorin calcium), 15 mg four times a day, and cholestyramine, 8 g three times a day, were administered. Three 1-g doses of intravenous methylprednisolone were given, along with amoxicillin with clavulanic acid in doses of 1.2 g intravenously three times daily. (There is no parenteral preparation of amoxicillin with clavulanic acid available in the United States.)

“This is the first-ever reported case of leflunomide-associated pneumonitis in a patient concurrently on rituximab and methotrexate. The patient was diagnosed early, therapy initiated promptly, and he survived the ordeal,” Dr. Jadon wrote. Leflunomide should be used with caution in patients with preexisting lung disease or in combination with rituximab and methotrexate, he said.

A third case, presented by Dr. Ahmad A. Al-Shami, was a 51-year-old woman diagnosed with RA at age 37. She was treated initially with steroids and azathioprine, but developed neutropenia, which necessitated withdrawal of the azathioprine. She later was started on sulfasalazine and then methotrexate in dosages of 22.5 mg/wk.

Because the disease remained active she was started on infliximab, but after two doses she developed fever and headache. The results of blood cultures, chest x-ray, and cerebrospinal fluid were normal, so she was restarted on infliximab but 3 months later she was readmitted with dyspnea, erythema nodosum, and ocular pruritus. The TNF blocker was once again stopped.

A chest x-ray at this time showed bilateral hilar lymphadenopathy, pulmonary function testing found reduced gas transfer, and a CT scan of the chest confirmed the hilar lymphadenopathy as well as mediastinal lymphadenopathy. Test results for tuberculosis and fungi were negative.

Transbronchial biopsy showed nonnecrotizing granulomatous inflammation, and she was diagnosed with sarcoidosis and treated with prednisone. “Hitherto there have been two case reports of pulmonary and extrapulmonary sarcoidosis, both in patients on etanercept, and we believe this is the first report on infliximab as a possible cause for sarcoidosis. We should be vigilant for this new adverse event,” wrote Dr. Al-Shami of University Hospitals of Leicester (England).

Finally, a 33-year-old man with stage IVB non-Hodgkin's lymphoma presented following a third cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. He had received a total of 2,190 mg of rituximab in three divided doses given at 21-day intervals, according to Dr. Charlotte M. Ford of the department of hematology, Newham University, London.

He had pyrexia, diarrhea, and a dry cough, along with clinical and radiologic evidence of left lower lobe pneumonia that persisted despite treatment with antibiotics and granulocyte colony-stimulating factor.

Adenovirus was isolated from bronchoalveolar lavage fluid, blood, and stool samples, and despite treatment with immunoglobulin and cidofovir plus intensive supportive care, he died on day 22.

Adenoviridae are lytic DNA viruses with varying degrees of pathogenicity, and infection is rarely fatal in otherwise healthy patients. “To our knowledge, this is the first case of fulminant adenovirus infection following rituximab therapy in doses similar to those used in the treatment of RA. Adenovirus infection should be considered in any patient presenting post rituximab with a febrile illness,” Dr. Ford wrote.

LIVERPOOL, ENGLAND — Serious and even fatal infections continue to occur in patients being treated with tumor necrosis factor-blocking agents and other biologics, emphasizing the need for heightened vigilance.

This was demonstrated in a series of posters presented at the annual meeting of the British Society for Rheumatology. In one case report, a 49-year-old woman with rheumatoid arthritis (RA) who had been treated unsuccessfully with methotrexate, sulfasalazine, leflunomide, and high doses of prednisone was started on etanercept. She developed lesions on her palms and soles typical of pustular psoriasis, and was then switched to infliximab, prednisone, and methotrexate. Following the third infusion she was hospitalized with fever and a widespread vesicular rash, according to Dr. Elizabeth A. Justice of University Hospital Birmingham (England).

The patient's C-reactive protein level was 153 mg/L, but the results of a sepsis screen and chest x-ray were normal. Fluid from the skin vesicles was found to contain herpes simplex virus type 1 (HSV-1).

The TNF blocker was stopped and acyclovir was given in dosages of 800 mg five times daily. The rash began to resolve within 48 hours, and after 2 weeks the acyclovir dosage was reduced to 400 mg twice daily.

Two months later she commenced adalimumab, 40 mg every other week, continuing on acyclovir prophylaxis in dosages of 200 mg every other day, with no recurrence of the HSV lesions.

“This is the first reported case of disseminated cutaneous HSV-1 infection following treatment with infliximab, an unusual adverse reaction we believe to be a direct result of her immunosuppressive therapy,” Dr. Justice wrote.

A second case involved a 49-year-old man with a 14-year history of seropositive nonerosive eosinophilic RA. He presented with shortness of breath but no cough, fever, or chest pain, said Dr. Deepak R. Jadon. The patient had been treated previously with etanercept and adalimumab with limited benefit, and 2 months earlier he had begun treatment with rituximab. He also had previously been on sulfasalazine for 13 years, but 2 months earlier switched to leflunomide, 10 mg/day, plus methotrexate, 15 mg/wk. He developed low-grade fever, tachycardia, dyspnea, and orthopnea, with end-inspiratory crackles audible bilaterally in the mid-lower chest. Arterial blood gases showed saturation of 75% and partial pressure of oxygen of 5.63 mm Hg. He also had neutrophilia and eosinopenia, and his C-reactive protein level was 174 mg/L.

A chest film showed patchy shadowing, and a CT scan revealed extensive ground glass parenchymal abnormalities affecting both mid and lower zones, according to Dr. Jadon of the department of rheumatology, Royal Berkshire Hospital, Reading (England).

Methotrexate and leflunomide were stopped, and calcium folinate (leucovorin calcium), 15 mg four times a day, and cholestyramine, 8 g three times a day, were administered. Three 1-g doses of intravenous methylprednisolone were given, along with amoxicillin with clavulanic acid in doses of 1.2 g intravenously three times daily. (There is no parenteral preparation of amoxicillin with clavulanic acid available in the United States.)

“This is the first-ever reported case of leflunomide-associated pneumonitis in a patient concurrently on rituximab and methotrexate. The patient was diagnosed early, therapy initiated promptly, and he survived the ordeal,” Dr. Jadon wrote. Leflunomide should be used with caution in patients with preexisting lung disease or in combination with rituximab and methotrexate, he said.

A third case, presented by Dr. Ahmad A. Al-Shami, was a 51-year-old woman diagnosed with RA at age 37. She was treated initially with steroids and azathioprine, but developed neutropenia, which necessitated withdrawal of the azathioprine. She later was started on sulfasalazine and then methotrexate in dosages of 22.5 mg/wk.

Because the disease remained active she was started on infliximab, but after two doses she developed fever and headache. The results of blood cultures, chest x-ray, and cerebrospinal fluid were normal, so she was restarted on infliximab but 3 months later she was readmitted with dyspnea, erythema nodosum, and ocular pruritus. The TNF blocker was once again stopped.

A chest x-ray at this time showed bilateral hilar lymphadenopathy, pulmonary function testing found reduced gas transfer, and a CT scan of the chest confirmed the hilar lymphadenopathy as well as mediastinal lymphadenopathy. Test results for tuberculosis and fungi were negative.

Transbronchial biopsy showed nonnecrotizing granulomatous inflammation, and she was diagnosed with sarcoidosis and treated with prednisone. “Hitherto there have been two case reports of pulmonary and extrapulmonary sarcoidosis, both in patients on etanercept, and we believe this is the first report on infliximab as a possible cause for sarcoidosis. We should be vigilant for this new adverse event,” wrote Dr. Al-Shami of University Hospitals of Leicester (England).

Finally, a 33-year-old man with stage IVB non-Hodgkin's lymphoma presented following a third cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. He had received a total of 2,190 mg of rituximab in three divided doses given at 21-day intervals, according to Dr. Charlotte M. Ford of the department of hematology, Newham University, London.

He had pyrexia, diarrhea, and a dry cough, along with clinical and radiologic evidence of left lower lobe pneumonia that persisted despite treatment with antibiotics and granulocyte colony-stimulating factor.

Adenovirus was isolated from bronchoalveolar lavage fluid, blood, and stool samples, and despite treatment with immunoglobulin and cidofovir plus intensive supportive care, he died on day 22.

Adenoviridae are lytic DNA viruses with varying degrees of pathogenicity, and infection is rarely fatal in otherwise healthy patients. “To our knowledge, this is the first case of fulminant adenovirus infection following rituximab therapy in doses similar to those used in the treatment of RA. Adenovirus infection should be considered in any patient presenting post rituximab with a febrile illness,” Dr. Ford wrote.

LIVERPOOL, ENGLAND — Serious and even fatal infections continue to occur in patients being treated with tumor necrosis factor-blocking agents and other biologics, emphasizing the need for heightened vigilance.

This was demonstrated in a series of posters presented at the annual meeting of the British Society for Rheumatology. In one case report, a 49-year-old woman with rheumatoid arthritis (RA) who had been treated unsuccessfully with methotrexate, sulfasalazine, leflunomide, and high doses of prednisone was started on etanercept. She developed lesions on her palms and soles typical of pustular psoriasis, and was then switched to infliximab, prednisone, and methotrexate. Following the third infusion she was hospitalized with fever and a widespread vesicular rash, according to Dr. Elizabeth A. Justice of University Hospital Birmingham (England).

The patient's C-reactive protein level was 153 mg/L, but the results of a sepsis screen and chest x-ray were normal. Fluid from the skin vesicles was found to contain herpes simplex virus type 1 (HSV-1).

The TNF blocker was stopped and acyclovir was given in dosages of 800 mg five times daily. The rash began to resolve within 48 hours, and after 2 weeks the acyclovir dosage was reduced to 400 mg twice daily.

Two months later she commenced adalimumab, 40 mg every other week, continuing on acyclovir prophylaxis in dosages of 200 mg every other day, with no recurrence of the HSV lesions.

“This is the first reported case of disseminated cutaneous HSV-1 infection following treatment with infliximab, an unusual adverse reaction we believe to be a direct result of her immunosuppressive therapy,” Dr. Justice wrote.

A second case involved a 49-year-old man with a 14-year history of seropositive nonerosive eosinophilic RA. He presented with shortness of breath but no cough, fever, or chest pain, said Dr. Deepak R. Jadon. The patient had been treated previously with etanercept and adalimumab with limited benefit, and 2 months earlier he had begun treatment with rituximab. He also had previously been on sulfasalazine for 13 years, but 2 months earlier switched to leflunomide, 10 mg/day, plus methotrexate, 15 mg/wk. He developed low-grade fever, tachycardia, dyspnea, and orthopnea, with end-inspiratory crackles audible bilaterally in the mid-lower chest. Arterial blood gases showed saturation of 75% and partial pressure of oxygen of 5.63 mm Hg. He also had neutrophilia and eosinopenia, and his C-reactive protein level was 174 mg/L.

A chest film showed patchy shadowing, and a CT scan revealed extensive ground glass parenchymal abnormalities affecting both mid and lower zones, according to Dr. Jadon of the department of rheumatology, Royal Berkshire Hospital, Reading (England).

Methotrexate and leflunomide were stopped, and calcium folinate (leucovorin calcium), 15 mg four times a day, and cholestyramine, 8 g three times a day, were administered. Three 1-g doses of intravenous methylprednisolone were given, along with amoxicillin with clavulanic acid in doses of 1.2 g intravenously three times daily. (There is no parenteral preparation of amoxicillin with clavulanic acid available in the United States.)

“This is the first-ever reported case of leflunomide-associated pneumonitis in a patient concurrently on rituximab and methotrexate. The patient was diagnosed early, therapy initiated promptly, and he survived the ordeal,” Dr. Jadon wrote. Leflunomide should be used with caution in patients with preexisting lung disease or in combination with rituximab and methotrexate, he said.

A third case, presented by Dr. Ahmad A. Al-Shami, was a 51-year-old woman diagnosed with RA at age 37. She was treated initially with steroids and azathioprine, but developed neutropenia, which necessitated withdrawal of the azathioprine. She later was started on sulfasalazine and then methotrexate in dosages of 22.5 mg/wk.

Because the disease remained active she was started on infliximab, but after two doses she developed fever and headache. The results of blood cultures, chest x-ray, and cerebrospinal fluid were normal, so she was restarted on infliximab but 3 months later she was readmitted with dyspnea, erythema nodosum, and ocular pruritus. The TNF blocker was once again stopped.

A chest x-ray at this time showed bilateral hilar lymphadenopathy, pulmonary function testing found reduced gas transfer, and a CT scan of the chest confirmed the hilar lymphadenopathy as well as mediastinal lymphadenopathy. Test results for tuberculosis and fungi were negative.

Transbronchial biopsy showed nonnecrotizing granulomatous inflammation, and she was diagnosed with sarcoidosis and treated with prednisone. “Hitherto there have been two case reports of pulmonary and extrapulmonary sarcoidosis, both in patients on etanercept, and we believe this is the first report on infliximab as a possible cause for sarcoidosis. We should be vigilant for this new adverse event,” wrote Dr. Al-Shami of University Hospitals of Leicester (England).

Finally, a 33-year-old man with stage IVB non-Hodgkin's lymphoma presented following a third cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. He had received a total of 2,190 mg of rituximab in three divided doses given at 21-day intervals, according to Dr. Charlotte M. Ford of the department of hematology, Newham University, London.

He had pyrexia, diarrhea, and a dry cough, along with clinical and radiologic evidence of left lower lobe pneumonia that persisted despite treatment with antibiotics and granulocyte colony-stimulating factor.

Adenovirus was isolated from bronchoalveolar lavage fluid, blood, and stool samples, and despite treatment with immunoglobulin and cidofovir plus intensive supportive care, he died on day 22.

Adenoviridae are lytic DNA viruses with varying degrees of pathogenicity, and infection is rarely fatal in otherwise healthy patients. “To our knowledge, this is the first case of fulminant adenovirus infection following rituximab therapy in doses similar to those used in the treatment of RA. Adenovirus infection should be considered in any patient presenting post rituximab with a febrile illness,” Dr. Ford wrote.

LIVERPOOL, ENGLAND — The majority of patients with ankylosing spondylitis being treated with anti-tumor necrosis factor agents in a routine care setting experienced improvements in disease activity after 6 months of treatment, according to Dr. Paul A. Lord of the University of Manchester (England).

Clinical trials have demonstrated the efficacy of these biologic drugs in ankylosing spondylitis (AS), but few data exist regarding the effectiveness in a real world setting.

Accordingly, the British Society for Rheumatology's Biologics Register began recruiting AS patients in 2002, recording baseline demographics, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores, as well as current and former drug treatments.

A total of 572 patients have been recruited, and data have now been analyzed for 261, with the primary outcome being changes in BASDAI and BASFI scores at 6 months.

The patients were predominantly young, with a median age of 43 years, and 81% were male. The median baseline BASDAI score was 7.6 and the median baseline BASFI score was 7.9. “They had severe disease,” Dr. Lord said at the annual meeting of the British Society for Rheumatology.

At 6 months, mean improvements of 3.5 and 2.7 U, respectively, were seen on BASDAI and BASFI. Additionally, 71% had improvements on BASDAI of at least 2 U, and 52% achieved a BASDAI 50 response, which represents a major clinical response, he said.

The first TNF blocker given was etanercept in 57%, infliximab in 36%, and adalimumab in 7%. Conventional disease-modifying antirheumatic drugs (DMARDs) also were being used by 54% and 55% of those on infliximab and adalimumab, respectively, compared with 37% of those on etanercept.

Lesser responses were seen in those with higher baseline BASFI scores, and women had a 1-U greater improvement on BASFI at 6 months compared with men.

Concurrent use of DMARDs was associated with improved functional status, demonstrated by a 0.8-U greater improvement on BASFI compared with those on monotherapy, but was not associated with absolute change in BASDAI.

Patients whose inflammatory markers were elevated at baseline had a 0.9-U greater response than those whose ESR and CRP level were normal at baseline, suggesting that these patients may be more responsive to anti-TNF therapy, Dr. Lord said.

Although the patients with baseline inflammatory markers had a better response to anti-TNF therapy, the benefits were not confined to this group, he noted.

Dr. Lord and his colleagues from the biologics register have reported no conflicts of interest.

LIVERPOOL, ENGLAND — The majority of patients with ankylosing spondylitis being treated with anti-tumor necrosis factor agents in a routine care setting experienced improvements in disease activity after 6 months of treatment, according to Dr. Paul A. Lord of the University of Manchester (England).

Clinical trials have demonstrated the efficacy of these biologic drugs in ankylosing spondylitis (AS), but few data exist regarding the effectiveness in a real world setting.

Accordingly, the British Society for Rheumatology's Biologics Register began recruiting AS patients in 2002, recording baseline demographics, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores, as well as current and former drug treatments.

A total of 572 patients have been recruited, and data have now been analyzed for 261, with the primary outcome being changes in BASDAI and BASFI scores at 6 months.

The patients were predominantly young, with a median age of 43 years, and 81% were male. The median baseline BASDAI score was 7.6 and the median baseline BASFI score was 7.9. “They had severe disease,” Dr. Lord said at the annual meeting of the British Society for Rheumatology.

At 6 months, mean improvements of 3.5 and 2.7 U, respectively, were seen on BASDAI and BASFI. Additionally, 71% had improvements on BASDAI of at least 2 U, and 52% achieved a BASDAI 50 response, which represents a major clinical response, he said.

The first TNF blocker given was etanercept in 57%, infliximab in 36%, and adalimumab in 7%. Conventional disease-modifying antirheumatic drugs (DMARDs) also were being used by 54% and 55% of those on infliximab and adalimumab, respectively, compared with 37% of those on etanercept.

Lesser responses were seen in those with higher baseline BASFI scores, and women had a 1-U greater improvement on BASFI at 6 months compared with men.

Concurrent use of DMARDs was associated with improved functional status, demonstrated by a 0.8-U greater improvement on BASFI compared with those on monotherapy, but was not associated with absolute change in BASDAI.

Patients whose inflammatory markers were elevated at baseline had a 0.9-U greater response than those whose ESR and CRP level were normal at baseline, suggesting that these patients may be more responsive to anti-TNF therapy, Dr. Lord said.

Although the patients with baseline inflammatory markers had a better response to anti-TNF therapy, the benefits were not confined to this group, he noted.

Dr. Lord and his colleagues from the biologics register have reported no conflicts of interest.

LIVERPOOL, ENGLAND — The majority of patients with ankylosing spondylitis being treated with anti-tumor necrosis factor agents in a routine care setting experienced improvements in disease activity after 6 months of treatment, according to Dr. Paul A. Lord of the University of Manchester (England).

Clinical trials have demonstrated the efficacy of these biologic drugs in ankylosing spondylitis (AS), but few data exist regarding the effectiveness in a real world setting.

Accordingly, the British Society for Rheumatology's Biologics Register began recruiting AS patients in 2002, recording baseline demographics, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores, as well as current and former drug treatments.

A total of 572 patients have been recruited, and data have now been analyzed for 261, with the primary outcome being changes in BASDAI and BASFI scores at 6 months.

The patients were predominantly young, with a median age of 43 years, and 81% were male. The median baseline BASDAI score was 7.6 and the median baseline BASFI score was 7.9. “They had severe disease,” Dr. Lord said at the annual meeting of the British Society for Rheumatology.

At 6 months, mean improvements of 3.5 and 2.7 U, respectively, were seen on BASDAI and BASFI. Additionally, 71% had improvements on BASDAI of at least 2 U, and 52% achieved a BASDAI 50 response, which represents a major clinical response, he said.

The first TNF blocker given was etanercept in 57%, infliximab in 36%, and adalimumab in 7%. Conventional disease-modifying antirheumatic drugs (DMARDs) also were being used by 54% and 55% of those on infliximab and adalimumab, respectively, compared with 37% of those on etanercept.

Lesser responses were seen in those with higher baseline BASFI scores, and women had a 1-U greater improvement on BASFI at 6 months compared with men.

Concurrent use of DMARDs was associated with improved functional status, demonstrated by a 0.8-U greater improvement on BASFI compared with those on monotherapy, but was not associated with absolute change in BASDAI.

Patients whose inflammatory markers were elevated at baseline had a 0.9-U greater response than those whose ESR and CRP level were normal at baseline, suggesting that these patients may be more responsive to anti-TNF therapy, Dr. Lord said.

Although the patients with baseline inflammatory markers had a better response to anti-TNF therapy, the benefits were not confined to this group, he noted.

Dr. Lord and his colleagues from the biologics register have reported no conflicts of interest.

LIVERPOOL, ENGLAND — B-cell depletion with rituximab showed benefits on magnetic resonance imaging for patients with active ankylosing spondylitis in a pilot study, but clinical effects were less pronounced, said Dr. Jonathan C. Packham of Keele (England) University.

Populations of CD20-positive B cells have been identified on histologic analysis of the spine in AS, and B-cell-producing germinal centers similar to those seen in RA have been found in the sacroiliac joints in AS, suggesting anti-CD20 treatment might have beneficial therapeutic effects. “We therefore performed a 6-month open-label study of rituximab … using MRI to evaluate its effects on spinal enthesitis,” Dr. Packham said at the annual meeting of the British Society for Rheumatology.

Rituximab was administered as two infusions of 1 g each, 2 weeks apart, in seven patients. Clinical assessments, made at four points during the study, included inflammatory markers, tender and swollen joint counts, patient global assessment, nocturnal and total back pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and AS quality of life (ASQOL).

At baseline, mean BASDAI and BASFI were 7.8 and 7.9, respectively, and all patients had C-reactive protein levels higher than 10 mg/dL. The mean number of sites of MRI-determined enthesitis/osteitis per patient fell by 49% between baseline and 6 months, from 19.4 to 9.9, which was statistically significant, Dr. Packham said. Significant improvements on MRI were seen in both lumbar spine and sacroiliac joints. The number of swollen joints fell from a mean of 3.9 to 2.6.

There was a nonsignificant trend in improvement in BASDAI and BASFI, with both indices decreased by 1.6 units over 6 months. There were no detectable changes in erythrocyte sedimentation rate, C-reactive protein, or ASQOL scores, however.

In an interview, Dr. Packham said he remains uncertain about whether these results represent a true effect of rituximab or the disease process itself settling down. “Levels of inflammation decreased by half on MRI, but this didn't appear to translate into clinical improvements. The response to rituximab does not seem to be as good as with anti-TNF agents in [AS],” he said. “But it's early days yet. Two other pilot studies are ongoing in Europe.”

Dr. Packham disclosed receiving an unrestricted educational grant from F. Hoffmann-La Roche Ltd.

LIVERPOOL, ENGLAND — B-cell depletion with rituximab showed benefits on magnetic resonance imaging for patients with active ankylosing spondylitis in a pilot study, but clinical effects were less pronounced, said Dr. Jonathan C. Packham of Keele (England) University.

Populations of CD20-positive B cells have been identified on histologic analysis of the spine in AS, and B-cell-producing germinal centers similar to those seen in RA have been found in the sacroiliac joints in AS, suggesting anti-CD20 treatment might have beneficial therapeutic effects. “We therefore performed a 6-month open-label study of rituximab … using MRI to evaluate its effects on spinal enthesitis,” Dr. Packham said at the annual meeting of the British Society for Rheumatology.

Rituximab was administered as two infusions of 1 g each, 2 weeks apart, in seven patients. Clinical assessments, made at four points during the study, included inflammatory markers, tender and swollen joint counts, patient global assessment, nocturnal and total back pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and AS quality of life (ASQOL).

At baseline, mean BASDAI and BASFI were 7.8 and 7.9, respectively, and all patients had C-reactive protein levels higher than 10 mg/dL. The mean number of sites of MRI-determined enthesitis/osteitis per patient fell by 49% between baseline and 6 months, from 19.4 to 9.9, which was statistically significant, Dr. Packham said. Significant improvements on MRI were seen in both lumbar spine and sacroiliac joints. The number of swollen joints fell from a mean of 3.9 to 2.6.

There was a nonsignificant trend in improvement in BASDAI and BASFI, with both indices decreased by 1.6 units over 6 months. There were no detectable changes in erythrocyte sedimentation rate, C-reactive protein, or ASQOL scores, however.

In an interview, Dr. Packham said he remains uncertain about whether these results represent a true effect of rituximab or the disease process itself settling down. “Levels of inflammation decreased by half on MRI, but this didn't appear to translate into clinical improvements. The response to rituximab does not seem to be as good as with anti-TNF agents in [AS],” he said. “But it's early days yet. Two other pilot studies are ongoing in Europe.”

Dr. Packham disclosed receiving an unrestricted educational grant from F. Hoffmann-La Roche Ltd.

LIVERPOOL, ENGLAND — B-cell depletion with rituximab showed benefits on magnetic resonance imaging for patients with active ankylosing spondylitis in a pilot study, but clinical effects were less pronounced, said Dr. Jonathan C. Packham of Keele (England) University.

Populations of CD20-positive B cells have been identified on histologic analysis of the spine in AS, and B-cell-producing germinal centers similar to those seen in RA have been found in the sacroiliac joints in AS, suggesting anti-CD20 treatment might have beneficial therapeutic effects. “We therefore performed a 6-month open-label study of rituximab … using MRI to evaluate its effects on spinal enthesitis,” Dr. Packham said at the annual meeting of the British Society for Rheumatology.

Rituximab was administered as two infusions of 1 g each, 2 weeks apart, in seven patients. Clinical assessments, made at four points during the study, included inflammatory markers, tender and swollen joint counts, patient global assessment, nocturnal and total back pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and AS quality of life (ASQOL).

At baseline, mean BASDAI and BASFI were 7.8 and 7.9, respectively, and all patients had C-reactive protein levels higher than 10 mg/dL. The mean number of sites of MRI-determined enthesitis/osteitis per patient fell by 49% between baseline and 6 months, from 19.4 to 9.9, which was statistically significant, Dr. Packham said. Significant improvements on MRI were seen in both lumbar spine and sacroiliac joints. The number of swollen joints fell from a mean of 3.9 to 2.6.

There was a nonsignificant trend in improvement in BASDAI and BASFI, with both indices decreased by 1.6 units over 6 months. There were no detectable changes in erythrocyte sedimentation rate, C-reactive protein, or ASQOL scores, however.

In an interview, Dr. Packham said he remains uncertain about whether these results represent a true effect of rituximab or the disease process itself settling down. “Levels of inflammation decreased by half on MRI, but this didn't appear to translate into clinical improvements. The response to rituximab does not seem to be as good as with anti-TNF agents in [AS],” he said. “But it's early days yet. Two other pilot studies are ongoing in Europe.”

Dr. Packham disclosed receiving an unrestricted educational grant from F. Hoffmann-La Roche Ltd.

LIVERPOOL, ENGLAND — Increasing experience with rituximab in patients with rheumatoid arthritis is showing that infection rates remain stable with repeat courses of treatment, Dr. Shouvik Dass has reported.

All patients who participated in the pivotal trials of rituximab in RA were entitled to enter into an open-label phase in which they can receive further courses of treatment, depending on disease activity.

As of September 2006, 1,053 RA patients had received rituximab. There are now 2,438 patient-years of exposure, with 400 patients having had three courses and 142 having had four, said Dr. Dass of the academic unit of musculoskeletal disease, University of Leeds (England).

Both adverse events and serious adverse events have decreased with each course. A total of 702 patients (67%) reported any infection; most were upper respiratory tract and urinary tract infections.

“Importantly, in the context of biologic therapy, there have been no opportunistic infections or cases of viral reactivation or tuberculosis,” Dr. Dass said at the annual meeting of the British Society for Rheumatology. Serious adverse event rates also are low and not changing through four courses, he said.

In all, 36 malignancies have been seen in 32 patients, four of which had fatal outcomes. “RA carries its own risk for malignancy, particularly lymphoproliferative disease, but there have been no lymphoproliferative malignancies and no evidence has emerged of increasing malignancies with repeated courses of treatment,” he said.

The B-cell depletion that occurs with rituximab therapy also raises concerns about the levels of immunoglobulins, secreted by plasma cells. Up to one-quarter of patients have low IgM by their fourth course of treatment. About 4%–5% have low IgG.

To determine if this decrease in immunoglobulin levels is clinically significant, infection rates were analyzed according to IgM and IgG levels. For patients with normal IgM, the serious infection rate was 4.9 per 100 patient-years, and for those with low IgM it was 6.4 per 100 patient years, a difference that was not statistically significant.

For IgG, the rate of all infections was 109 per 100 patient-years in patients with the lowest levels of IgG, and 63 per 100 patient years among those who had the highest levels, a significant difference, Dr. Dass said.

The rates of serious infections, however, were similar, with 6.8 per 100 patient-years in the lowest IgG group and 5 per 100 patient-years in the highest IgG group.

These findings are consistent with earlier data. “We need to see if there is any further association between changes in immunoglobulins and risk of infection and whether in the future that will affect our clinical practice,” he said.

Dr. Dass declared no conflicts.

LIVERPOOL, ENGLAND — Increasing experience with rituximab in patients with rheumatoid arthritis is showing that infection rates remain stable with repeat courses of treatment, Dr. Shouvik Dass has reported.

All patients who participated in the pivotal trials of rituximab in RA were entitled to enter into an open-label phase in which they can receive further courses of treatment, depending on disease activity.

As of September 2006, 1,053 RA patients had received rituximab. There are now 2,438 patient-years of exposure, with 400 patients having had three courses and 142 having had four, said Dr. Dass of the academic unit of musculoskeletal disease, University of Leeds (England).

Both adverse events and serious adverse events have decreased with each course. A total of 702 patients (67%) reported any infection; most were upper respiratory tract and urinary tract infections.

“Importantly, in the context of biologic therapy, there have been no opportunistic infections or cases of viral reactivation or tuberculosis,” Dr. Dass said at the annual meeting of the British Society for Rheumatology. Serious adverse event rates also are low and not changing through four courses, he said.

In all, 36 malignancies have been seen in 32 patients, four of which had fatal outcomes. “RA carries its own risk for malignancy, particularly lymphoproliferative disease, but there have been no lymphoproliferative malignancies and no evidence has emerged of increasing malignancies with repeated courses of treatment,” he said.

The B-cell depletion that occurs with rituximab therapy also raises concerns about the levels of immunoglobulins, secreted by plasma cells. Up to one-quarter of patients have low IgM by their fourth course of treatment. About 4%–5% have low IgG.

To determine if this decrease in immunoglobulin levels is clinically significant, infection rates were analyzed according to IgM and IgG levels. For patients with normal IgM, the serious infection rate was 4.9 per 100 patient-years, and for those with low IgM it was 6.4 per 100 patient years, a difference that was not statistically significant.

For IgG, the rate of all infections was 109 per 100 patient-years in patients with the lowest levels of IgG, and 63 per 100 patient years among those who had the highest levels, a significant difference, Dr. Dass said.

The rates of serious infections, however, were similar, with 6.8 per 100 patient-years in the lowest IgG group and 5 per 100 patient-years in the highest IgG group.

These findings are consistent with earlier data. “We need to see if there is any further association between changes in immunoglobulins and risk of infection and whether in the future that will affect our clinical practice,” he said.

Dr. Dass declared no conflicts.

LIVERPOOL, ENGLAND — Increasing experience with rituximab in patients with rheumatoid arthritis is showing that infection rates remain stable with repeat courses of treatment, Dr. Shouvik Dass has reported.

All patients who participated in the pivotal trials of rituximab in RA were entitled to enter into an open-label phase in which they can receive further courses of treatment, depending on disease activity.

As of September 2006, 1,053 RA patients had received rituximab. There are now 2,438 patient-years of exposure, with 400 patients having had three courses and 142 having had four, said Dr. Dass of the academic unit of musculoskeletal disease, University of Leeds (England).

Both adverse events and serious adverse events have decreased with each course. A total of 702 patients (67%) reported any infection; most were upper respiratory tract and urinary tract infections.

“Importantly, in the context of biologic therapy, there have been no opportunistic infections or cases of viral reactivation or tuberculosis,” Dr. Dass said at the annual meeting of the British Society for Rheumatology. Serious adverse event rates also are low and not changing through four courses, he said.

In all, 36 malignancies have been seen in 32 patients, four of which had fatal outcomes. “RA carries its own risk for malignancy, particularly lymphoproliferative disease, but there have been no lymphoproliferative malignancies and no evidence has emerged of increasing malignancies with repeated courses of treatment,” he said.

The B-cell depletion that occurs with rituximab therapy also raises concerns about the levels of immunoglobulins, secreted by plasma cells. Up to one-quarter of patients have low IgM by their fourth course of treatment. About 4%–5% have low IgG.

To determine if this decrease in immunoglobulin levels is clinically significant, infection rates were analyzed according to IgM and IgG levels. For patients with normal IgM, the serious infection rate was 4.9 per 100 patient-years, and for those with low IgM it was 6.4 per 100 patient years, a difference that was not statistically significant.

For IgG, the rate of all infections was 109 per 100 patient-years in patients with the lowest levels of IgG, and 63 per 100 patient years among those who had the highest levels, a significant difference, Dr. Dass said.

The rates of serious infections, however, were similar, with 6.8 per 100 patient-years in the lowest IgG group and 5 per 100 patient-years in the highest IgG group.

These findings are consistent with earlier data. “We need to see if there is any further association between changes in immunoglobulins and risk of infection and whether in the future that will affect our clinical practice,” he said.

Dr. Dass declared no conflicts.

LIVERPOOL, ENGLAND — Patients with rheumatoid arthritis who have a history of cigarette smoking are more likely to have a poor response to anti-tumor necrosis factor therapy than are those who have never smoked.

Recent studies have provided strong evidence that cigarette smoking is a risk factor in susceptibility to rheumatoid arthritis (RA) and more severe disease. Smokers with RA appear to have increased production of cytokines such as tumor necrosis factor, and autoantibodies such as rheumatoid factor. A recent study from the British Society for Rheumatology's biologics register found that patients who were current smokers had a low response rate to infliximab (Rheumatology [Oxford] 2006;45:1558–65).

“To see if smoking affects the response to therapy in our patients and to determine if there is a relationship between response and pack-year history, we collected demographic data and smoking histories for all patients at our hospital who were started on anti-TNF drugs since 2002,” reported Dr. Derek L. Mattey of Staffordshire Rheumatology Centre, University Hospital of North Staffordshire, Stoke-on-Trent, England.

A total of 154 patients whose mean age was 65 years were included. Infliximab was the agent used by 83 patients, etanercept by 55, and adalimumab by 16.

Two-thirds of the patients reported ever having smoked, but only 25% were still current smokers at the time they initiated treatment. The extent of previous smoking was quantified, with one pack-year being equivalent to 20 cigarettes per day for 1 year, and intensity of smoking stratified as never (0 pack-years), light (1–15 pack-years), moderate (16–30 pack-years), and heavy (more than 30 pack-years).

At baseline, smokers were more likely to be rheumatoid factor positive and have nodular disease, but smokers and nonsmokers did not differ in baseline Disease Activity Score (DAS) 28, Health Assessment Questionnaire (HAQ) scores, pain scores, or C-reactive protein level, Dr. Mattey said.

Response was defined according to the EULAR improvement criteria, based on 3-month DAS28.

At 3 months, there were significant differences between the groups, with patients whose smoking history exceeded 30 pack-years having an odds ratio of 7.4 for nonresponse compared with patients who had never smoked. The odds ratios for those in the light and moderate groups were 1.9 and 1.8, respectively.

Multivariate logistic regression analysis showed that the association of pack-year history with nonresponse was independent of age, sex, disease duration, baseline DAS28, and HAQ scores.

LIVERPOOL, ENGLAND — Patients with rheumatoid arthritis who have a history of cigarette smoking are more likely to have a poor response to anti-tumor necrosis factor therapy than are those who have never smoked.

Recent studies have provided strong evidence that cigarette smoking is a risk factor in susceptibility to rheumatoid arthritis (RA) and more severe disease. Smokers with RA appear to have increased production of cytokines such as tumor necrosis factor, and autoantibodies such as rheumatoid factor. A recent study from the British Society for Rheumatology's biologics register found that patients who were current smokers had a low response rate to infliximab (Rheumatology [Oxford] 2006;45:1558–65).

“To see if smoking affects the response to therapy in our patients and to determine if there is a relationship between response and pack-year history, we collected demographic data and smoking histories for all patients at our hospital who were started on anti-TNF drugs since 2002,” reported Dr. Derek L. Mattey of Staffordshire Rheumatology Centre, University Hospital of North Staffordshire, Stoke-on-Trent, England.

A total of 154 patients whose mean age was 65 years were included. Infliximab was the agent used by 83 patients, etanercept by 55, and adalimumab by 16.

Two-thirds of the patients reported ever having smoked, but only 25% were still current smokers at the time they initiated treatment. The extent of previous smoking was quantified, with one pack-year being equivalent to 20 cigarettes per day for 1 year, and intensity of smoking stratified as never (0 pack-years), light (1–15 pack-years), moderate (16–30 pack-years), and heavy (more than 30 pack-years).

At baseline, smokers were more likely to be rheumatoid factor positive and have nodular disease, but smokers and nonsmokers did not differ in baseline Disease Activity Score (DAS) 28, Health Assessment Questionnaire (HAQ) scores, pain scores, or C-reactive protein level, Dr. Mattey said.

Response was defined according to the EULAR improvement criteria, based on 3-month DAS28.

At 3 months, there were significant differences between the groups, with patients whose smoking history exceeded 30 pack-years having an odds ratio of 7.4 for nonresponse compared with patients who had never smoked. The odds ratios for those in the light and moderate groups were 1.9 and 1.8, respectively.

Multivariate logistic regression analysis showed that the association of pack-year history with nonresponse was independent of age, sex, disease duration, baseline DAS28, and HAQ scores.

LIVERPOOL, ENGLAND — Patients with rheumatoid arthritis who have a history of cigarette smoking are more likely to have a poor response to anti-tumor necrosis factor therapy than are those who have never smoked.

Recent studies have provided strong evidence that cigarette smoking is a risk factor in susceptibility to rheumatoid arthritis (RA) and more severe disease. Smokers with RA appear to have increased production of cytokines such as tumor necrosis factor, and autoantibodies such as rheumatoid factor. A recent study from the British Society for Rheumatology's biologics register found that patients who were current smokers had a low response rate to infliximab (Rheumatology [Oxford] 2006;45:1558–65).

“To see if smoking affects the response to therapy in our patients and to determine if there is a relationship between response and pack-year history, we collected demographic data and smoking histories for all patients at our hospital who were started on anti-TNF drugs since 2002,” reported Dr. Derek L. Mattey of Staffordshire Rheumatology Centre, University Hospital of North Staffordshire, Stoke-on-Trent, England.

A total of 154 patients whose mean age was 65 years were included. Infliximab was the agent used by 83 patients, etanercept by 55, and adalimumab by 16.

Two-thirds of the patients reported ever having smoked, but only 25% were still current smokers at the time they initiated treatment. The extent of previous smoking was quantified, with one pack-year being equivalent to 20 cigarettes per day for 1 year, and intensity of smoking stratified as never (0 pack-years), light (1–15 pack-years), moderate (16–30 pack-years), and heavy (more than 30 pack-years).

At baseline, smokers were more likely to be rheumatoid factor positive and have nodular disease, but smokers and nonsmokers did not differ in baseline Disease Activity Score (DAS) 28, Health Assessment Questionnaire (HAQ) scores, pain scores, or C-reactive protein level, Dr. Mattey said.

Response was defined according to the EULAR improvement criteria, based on 3-month DAS28.

At 3 months, there were significant differences between the groups, with patients whose smoking history exceeded 30 pack-years having an odds ratio of 7.4 for nonresponse compared with patients who had never smoked. The odds ratios for those in the light and moderate groups were 1.9 and 1.8, respectively.

Multivariate logistic regression analysis showed that the association of pack-year history with nonresponse was independent of age, sex, disease duration, baseline DAS28, and HAQ scores.