BIRMINGHAM, England - Methotrexate is not disease modifying in patients with psoriatic arthritis, and it has a borderline effect on psoriatic arthritis response criteria.
Placebo-controlled trial findings show that although methotrexate therapy results in some symptomatic improvement after 6 months of therapy, the drug has little effect on measures that suggest disease modification, including joint swelling and the acute phase response.
These findings call into question the use of methotrexate monotherapy in psoriatic arthritis and should herald in a change in U.K. guidelines and National Institute for Health and Clinical Excellence recommendations, said Dr. Gabrielle S. Kingsley at the annual meeting of the British Society for Rheumatology.
In the United Kingdom, the use of biologic agents in psoriatic arthritis was possible only after treatment with two disease-modifying antirheumatic drugs (DMARDs) had failed, said Dr. Kingsley of the division of immunology, infection, and inflammatory diseases at King's College London and consultant rheumatologist at the Lewisham Hospital NHS Trust, London.
"But why should people have to take sulfasalazine and methotrexate, which are primarily symptom-modifying drugs, in order to get access to something which might be better?" Dr. Kinglsey asked.
In the double-blind, multicenter MIPA (Methotrexate in Psoriatic Arthritis) trial, patients with active psoriatic arthritis were randomized to treatment with methotrexate at a dose of 15 mg/week (n = 109) or to placebo (n = 112) for 6 months. The mean age of patients was 49 years, and their median disease duration was 5 years.
Around one-third of patients in each arm withdrew because of adverse events or for other reasons, with the result that 71 methotrexate- and 77 placebo-treated patients completed the trial.
The primary outcome measure was change in psoriatic arthritis response criteria (PsARC). This was improved with methotrexate treatment when compared with placebo. However, because only two out of four outcome criteria need to be improved, "this is a fairly low hurdle to jump over," Dr. Kingsley said. American College of Rheumatology-20 criteria at 6 months were not improved, and neither the PsARC nor the ACR-20 criteria were improved by methotrexate after 3 months' therapy.
Looking at the individual components of PsARC - tender joint count, swollen joint count, patient global assessment and physician global assessment - only the symptomatic parameters were significantly improved by methotrexate when compared with placebo.
"Rheumatologists need to reappraise how they use methotrexate, and indeed sulfasalazine, neither of which are truly disease-modifying drugs, and they should be considering using other options," Dr. Kingsley said. She noted that the NICE treatment pathway for psoriatic arthritis should be reevaluated.
"Methotrexate is widely used in psoriatic arthritis almost entirely based on the fact that it works in rheumatoid arthritis," Dr. Kingsley said. Before the MIPA trial, no randomized, controlled trial had looked at the role of methotrexate in psoriatic arthritis because it was widely believed that the drug was effective. She added that the MIPA trial results had vindicated the use of a placebo-controlled design, and had shown that "if you are going to have treatment pathways, these do need to be based on solid evidence."
Dr. Deborah E. Bax, BSR president and consultant physician in rheumatology at the Royal Hallamshire Hospital in Sheffield, England, commented, "These results are very thought provoking. They question our clinical practice and could have huge implications for us and for our patients."
"I don't think these results are practice changing at the moment," commented Dr. Philip S. Helliwell, senior lecturer in rheumatology at Leeds (England ) University. Dr. Helliwell observed that the distinction between oligo- and polyarticular disease was not made, which could have diluted the findings.
Dr. Helliwell also said that the dose of methotrexate, although standard at the time the MIPA trial began, was possibly too low to have an effect. He noted that very good results were currently being obtained with methotrexate at doses of up to 25 mg/week in an ongoing trial of intensive vs. routine treatment psoriatic arthritis.
Disclosures: Dr. Kingsley, Dr. Bax, and Dr. Helliwell had no relevant financial disclosures. Arthritis Research UK funded the trial.