CHICAGO—Methotrexate is a commonly used disease-modifying antirheumatic drug (DMARD) for treating patients with psoriatic arthritis (PsA). However, is it truly as effective as many think it is?
That’s the question that Gabrielle Kingsley, MB, PhD, consultant and reader in rheumatology at Kings College in London and Lewisham Healthcare NHS Trust, raised during the session, “Spondylarthropathies: Recent Insights,” which took place at the 2011 ACR/ARHP Annual Scientific Meeting in November. [Editor’s note: This session was recorded and is available via ACR SessionSelect at www.rheumatology.org.]
A number of PsA treatment guidelines include methotrexate, Dr. Kingsley said. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis recommend methotrexate to treat peripheral disease and skin and nail disease in PsA, she noted. Guidelines from the Scottish Intercollegiate Guidelines Network state that dermatology and rheumatology teams should work together to use methotrexate in PsA for the treatment of severe cutaneous psoriasis and peripheral disease. Recommendations from the European League Against Rheumatism published last year also provide a role for methotrexate in PsA after nonsteroidal antiinflammatory drugs (NSAIDs) and glucocorticoid injections are used, Dr. Kingsley said.
“All of these guidelines have methotrexate, which implies a strong evidence base. The reality is somewhat different,” she said. Dr. Kingsley went on to explain that methotrexate seems to help symptoms in PsA patients but does not usually improve patient outcomes.
Dr. Kingsley reviewed the results of the Norwegian NOR-DMARD study that included 430 patients with PsA and 1,218 with rheumatoid arthritis (RA).1 Because it is known that methotrexate is effective in RA patients, it would make sense that it would have a similar effect on PsA patients, Dr. Kingsley said. The study found similar improvements in most measures for both patient groups, but when the data were adjusted for baseline, gender, and other factors, there was less improvement in the PsA patients, she said. However, changes were within the same range as they were for RA patients.
Dr. Kingsley then spoke of a randomized clinical trial in which she was involved that compared methotrexate with placebo in 221 PsA patients. Half of the patients had 15 mg of methotrexate a week, while the other half had the placebo. The investigators then looked at composite measures over six months.
The researchers found that, while methotrexate made improvements in symptom modification, it did not make statistically significant improvements with outcomes such as swollen joint count and tender joint count.
Dr. Kingsley said that the trial had some limitations, such as a smaller size and not being powered to study specific PsA subtypes, and that large doses of 20 to 25 mg a week of methotrexate may be needed for stronger results. She also said the NOR-DMARD study is limited because it is observational and does not have a control group.
Methotrexate may be effective in RA patients but not PsA patients because of different pathological processes involved, Dr. Kingsley said. “We still don’t know how methotrexate works, but we know the different things it can do chemically,” she said.
Tracking Reactive Arthritis
Rheumatologists should be ever vigilant for reactive arthritis, said John Carter, MD, associate professor of medicine at the University of South Florida in Tampa. Dr. Carter focused his presentation on reactive arthritis. Postdysentery reactive arthritis occurs in 1.5% to 30% of cases with exposure to Salmonella, Shigella, Campylobacter, and Yersinia bacteria, Dr. Carter said. There is also a postvenereal (Chlamydia-related) attack rate of about 4%.
With an estimated 3-million Chlamydia cases in the United States each year, there should be about 123,000 cases of reactive arthritis annually, just for postvenereal cases, Dr. Carter said. “When you compare [the numbers] to rheumatoid arthritis, they really should rival each other,” he said. Tracking the frequency of reactive arthritis becomes more complicated because many cases don’t present with classic symptoms. It is even likely that some cases of undifferentiated spondyloarthritis are secondary to Chlamydia, Dr. Carter said.
He discussed various treatment options for reactive arthritis. Many patients are still given NSAIDs or DMARDs. Corticosteroids can be a treatment option, “but reactive patients tend to not respond as do [patients with] some other types of inflammatory arthritis,” Dr. Carter said. There is also research into the use of antibiotics to treat reactive arthritis. Early research in this area found mostly negative results, likely because postdysentery and post-Chlamydia patients were grouped together.
Subsequent research has taken a closer look at combination antibiotic therapy, such as one study by Dr. Carter and colleagues that tested doxycycline versus doxycycline and rifampin.2 The six variables studied in the investigation, such as back pain and tender joint count, improved in the patients receiving combination therapy versus the ones receiving doxycycline only.
A more recent double-blind, placebo-controlled, prospective study by Dr. Carter and colleagues that had 42 participants randomized for treatment found that 63% of those on antibiotic combination therapy were responders versus only 20% on placebo.3 That study compared azithromycin and rifampin plus placebo instead of doxycycline; doxycycline and rifampin and placebo instead of azithromycin; and placebo only.
“Combination antibiotics show promise at ameliorating the symptoms of Chlamydia reactive arthritis and eliminating the persistent state of Chlamydia,” Dr. Carter said.
TNF Treatment
A third presentation at the session, given by Walter P. Maksymowych, MD, professor of medicine in the division of rheumatology at the University of Alberta in Edmonton, Canada, focused tumor necrosis factor (TNF) inhibition and structural damage progression in ankylosing spondylitis. He reported that anti-TNF therapy does not seem to show the same positive results in ankylosing spondylitis patients as it does in RA patients. He hypothesized that in individual patients, the effect of anti-TNF therapy on radiographic progression depends on the relative number of acute and mature inflammatory lesions. “Early diagnosis is a prerequisite for advances in disease modification,” he said. the rheumatologist
Vanessa Caceres is a freelance medical writer in Bradenton, Fla.
References
- Lie E, van der Heijde D, Uhlig T, et al. Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2010;69:671-676.
- Carter JD, Valeriano J, Vasey FB. Doxycycline versus doxycycline and rifampin in undifferentiated spondyloarthropathy, with special reference to chlamydia-induced arthritis. A prospective, randomized 9-month comparison. J Rheumatol. 2004;31:1973-1980.
- Carter JD, Espinoza LR, Inman RD, et al. Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: A double-blind, placebo-controlled, prospective trial. Arthritis Rheum. 2010;62:1298-1307.
