Methotrexate's adverse event profile in psoriatic arthritis was different from that in rheumatoid arthritis in a study of more than 1,000 “everyday” patients treated in 30 rheumatology clinics across 13 countries.
“We have suspected for some time that there is differential toxicity, but the studies have not been based in 'everyday practice,' so these data help,” said lead investigator Dr. Philip Helliwell of the University of Leeds (England) in an interview.
In a study that sought to characterize both drug use patterns and side effect profiles in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, Dr. Helliwell and his colleague, Dr. William J. Taylor, of the University of Otago, Wellington (New Zealand), looked at enrollees in the Classification Criteria for Psoriatic Arthritis (CASPAR) study, including 588 consecutive clinic attendees with PsA and 536 controls, who were also clinic attendees with some form of inflammatory arthritis, most often RA.
Details about drug therapy were unavailable for 12% of PsA and 2% of RA patients. However, in the cases where treatment was known, methotrexate (MTX) was the most often prescribed first-line therapy in both diseases, given as the initial therapy to 39% of patients with PsA and 29% of RA patients. The second most often prescribed first-line therapy was sulfasalazine in PsA and corticosteroids in RA (J. Rheum 2008 Jan. 15 [Epub before print]).
Of the 404 patients with psoriatic arthritis who were still taking pharmacotherapy at the study's conclusion, 23% were treated with combination therapy. The most frequent combinations were “MTX/sulfasalazine (33 cases), MTX/steroids (22 cases), and MTX/anti-TNF (16 cases),” wrote the researchers. Triple drug therapy was used in nine PsA patients.
Combination therapy was used in 45% of the 315 RA patients still taking drugs at the study's end, with the most often prescribed regimens being MTX/corticosteroids (74 cases), MTX/antimalarials (33 cases), MTX/sulfasalazine (22 cases), and MTX/anti-TNF (13 cases). Triple drug therapy was used in 26 cases.
Methotrexate monotherapy was used through the study's completion by “a majority … over 50%,” said Dr. Helliwell.
According to Dr. Helliwell, methotrexate's popularity is despite the fact that it is prescribed “off-label” for both PsA and RA in the United Kingdom. “The people who make methotrexate have no incentive to seek regulatory approval because everybody is using it anyway, and [getting approval] is an expensive process,” he said.
In the United States, methotrexate has Food and Drug Administration approval for the treatment of psoriasis and rheumatoid arthritis, including Polyarticular-Course Juvenile Rheumatoid Arthritis, and neoplastic diseases, according to a representative of the Center for Drug Evaluation for Research at the FDA.
As for the second goal of the study—to ascertain the adverse event profile in each drug—the researchers found that while some events were common to both diseases, like renal problems with cyclosporine and gold salts, and skin problems with antimalarials and gold salts, “pulmonary toxicity seen with MTX was confined to the patients with RA,” affecting 4% of RA patients vs. 1% of PsA cases. Also, “although MTX is infrequently discontinued for reasons of inefficacy in both diseases, it was more often discontinued in PsA compared to RA, primarily for reasons of toxicity.”
Hepatic adverse events occurred in 7% of PsA cases vs. 4% of RA cases. “The problem of hepatotoxicity and methotrexate is of particular concern with psoriasis. Dermatologists seem to see much more hepatotoxicity than we as rheumatologists,” said Dr. Helliwell.
“Treatment trials are constrained in ways that may detract from the use of the drug in everyday practice—patients entered into trials are often a very select group with little comorbidity, which confounds extrapolation of drug use to a wide spectrum of patients,” wrote the authors.
Dr. Helliwell reported no conflicts of interest in relation to this study.