Treatment with methotrexate, the cornerstone disease-modifying therapy in rheumatoid arthritis, had no benefit on synovitis in patients with psoriatic arthritis, a placebo-controlled trial found.

After adjustment for age, sex, and duration of disease, 6 months of methotrexate treatment had no statistically significant benefit as measured on the psoriatic arthritis response criteria, according to Gabrielle H. Kingsley, MD, of King's College London, and colleagues.

However, the treatment did show benefits on patient global assessment and on physician global assessment, "suggesting it may have symptom-modifying effects," the researchers reported in the August issue of Rheumatology.

Methotrexate has come to be considered a standard treatment in psoriatic arthritis, being recommended in recent guidelines, yet the drug has never demonstrated efficacy for this condition in a randomized clinical trial.

Because other treatments such as tumor necrosis factor inhibitors have been proven effective in psoriatic arthritis, and because methotrexate is not without potential toxicity, Kingsley and colleagues undertook a blinded study to clarify the role for methotrexate in this disorder.

Beginning in 2003, they enrolled 221 patients who received methotrexate in a target dosage of 15 mg per week or matched placebo.

The patient population was predominantly male, with a mean age of about 48 years. Disease duration was approximately 12 months.

More than 80 percent of participants also were taking nonsteroidal anti-inflammatory drugs.

After 6 months of treatment, there was no significant effect seen when overall efficacy was assessed on the American College of Rheumatology 20 percent improvement criteria or on the disease activity score in 28 joints, the researchers reported.

A minimum odds ratio showing efficacy would be 2.7, they explained.

Objective individual outcome measures were also evaluated, and no significant effects were seen for tender and swollen joint counts, pain, functional status, erythrocyte sedimentation rate, or C-reactive protein.

The researchers also analyzed the data according to whether patients had oligoarticular or polyarticular disease, and found no difference.

A total of nine patients receiving methotrexate withdrew from the study because of adverse events, as did seven on placebo.

Nausea and vomiting were reported by more than twice as many patients on methotrexate (38 versus 16), while liver function test abnormalities were seen in 12 methotrexate patients and in two placebo patients.

The researchers concluded that, despite some symptomatic and cutaneous benefits, their finding of a lack of effect for synovitis means methotrexate can't be considered to have "a true disease-modifying effect" in psoriatic arthritis.

Other treatments actually have been found to have disease-modifying effects in clinical trials, such as leflunomide (Arava), which had an odds ratio of 3.4 for benefit, and etanercept (Enbrel), with an odds ratio above 20.

The researchers conceded that their trial may have not been sufficiently large to detect small improvements, but did not believe further study would be needed.

"We believe a larger trial would not only be impractical but also would be unwarranted in the face of more effective alternatives," they stated.

"We also think that guidelines for treating [psoriatic arthritis] need to be revisited so that the sequencing of conventional drugs before biologics are used is reevaluated," they added.

They noted that certain questions have yet to be answered, such as whether methotrexate could be used in combination with biologics or other disease-modifying drugs in psoriatic arthritis, and whether there are patterns of disease that might tend to show a better response.

Source: RA Drug Fails to Curb Psoriatic Arthritis