A ritish study raises questions about whether methotrexate – a disease-modifying antirheumatic drug and a first-line treatment for psoriatic arthritis, or PsA – actually does anything to slow down the disease.

The study, published in the August 2012 issue of the journal Rheumatology, is the first large, double-blind, placebo-controlled study of methotrexate,or MTX, for psoriatic arthritis.

A total of 221 PsA patients were recruited from 22 specialty rheumatology clinics in the U.K. For six months, the subjects received either methotrexate, with a target dose of 15 milligrams per week, or a placebo. Various measures of effectiveness were tallied at three and six months.

After six months, the researchers found methotrexate had no significant effect on objective measures of disease activity. But it did seem to offer subjective benefits for some – that is, doctors and patients seemed to agree the drug was beneficial based on doctor observation and how the patients reported they felt.

To grasp a firmer understanding of this research, we followed up with study co-author, Dr. Gabrielle Kingsley, consultant and reader in the department of rheumatology at Kings College, London.

Q&A:

Arthritis Today: So what did your study determine about the role of methotrexate in psoriatic arthritis therapy?

Dr. Kingsley: “We believe it is not a disease modifying anti-rheumatic drug [or DMARD] but a symptom-modifier in PsA, not that it has no effect at all. We also saw effects on the skin, which has been well demonstrated before.”

AT: Do you feel the study was slightly limited by the six-month duration of the therapy?

Dr. Kingsley: “Methotrexate might have worked in a longer study, but we were limited to six months because it was felt the use of placebo for a longer period might not be ethical. Methotrexate might (also) have worked at a higher dose than we used.” However, Dr. Kingsley notes the 15 milligrams a week used in this study is comparable to the effective dose used for rheumatoid arthritis in other clinical trials – and is an effective dose for skin psoriasis.

AT: Were specific subtypes of psoriatic arthritis targeted in the study?

Dr. Kingsley: “A study which was powered to recruit enough patients with each different subtype of psoriatic arthritis would have been enormous and impractical. We did not intend to differentiate among the different subtypes as the paper makes clear.” But, she notes, a simple analysis between polyarticular and oligoarticular diseases showed no difference in drug response.

AT: Did the study look at methotrexate in combination therapy with, for example, a biologic agent, which is sometimes used when monotherapy fails?

Dr. Kingsley: “We didn’t look at methotrexate in combination therapy, which the TICOPA study is doing. There is already a combination study, RESPOND, which compares MTX plus infliximab against MTX alone, but that is really a study of infliximab, since both groups had MTX.”

AT:  How clinically relevant do you think the results of this study are?

Dr. Kingsley: “The patients recruited to the study were very similar in all clinical and disease activity measures to those psoriatic arthritis patients recruited to the NOR-DMARD study, a large Norwegian observational study of patients with various sorts of inflammatory arthritis who were starting methotrexate. Therefore the study seems generalizable to routine patients.” Dr. Kingsley adds that the only other randomized controlled trial of methotrexate in PsA, though a small one, showed similar results – that is, no significant effect on synovitis vs. placebo – and that there are no randomized controlled trials that show an effect on synovitis for low-dose oral methotrexate in PsA.