Use of Methotrexate Questioned for Psoriatic Arthritis
A study tackles "difficult clinical question," finding a cornerstone treatment may provide symptom relief, but not much more.
Methotrexate – a disease-modifying antirheumatic drug – is considered a first-line treatment for psoriatic arthritis, or PsA, but a British study raises questions about whether it actually does anything to slow down the disease.
The study, published in 2012 in the journal Rheumatology, is the first large, double-blind, placebo-controlled study of methotrexate for psoriatic arthritis. This study design means half the subjects received methotrexate and half received placebo – and neither the study subjects nor the researchers knew who was getting which medication. This kind of study design is widely considered “the gold standard” because it eliminates bias.
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. These measures included the PsA response criteria, or PsARC, which looks at the number of tender and swollen joints, as well as patient and physician assessments of disease progress; the disease activity score for 28 joints, or DAS-28, which assess tenderness and swelling in 28 joints; as well as blood tests that measure inflammation. Seventy of the subjects either dropped out or were lost to follow-up.
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.
Bernard Rubin, DO, division head for rheumatology at the Henry Ford Hospital in Detroit, says that’s not an unimportant consideration. “Do many patients on methotrexate feel better? My perception is they do. There are a lot of measures of patient global well-being. If the patient feels better, that is one of your outcomes,” says Dr. Rubin, who was not involved in the study.
Dr. Rubin applauds the British study because he says it tried to answer a difficult clinical question – but he notes that the study has flaws. He says one of the major problems is that it “took all-comers” with psoriatic arthritis when in fact the disease is highly variable. “There are very different subsets of psoriatic arthritis. Some have just a few joints involved, some have disease resembling something like rheumatoid arthritis,” he says. Dr. Rubin has found methotrexate does provide symptomatic relief to some of his patients with multiple joint involvement and psoriasis.
Eric Matteson, MD, chair of rheumatology at the Mayo Clinic in Rochester, Minn, says he has had similar experiences. “In my view and experience, methotrexate does work for individual patients with peripheral joint disease, especially in the hands and feet,” he says.
The study results mirror that of another, similar – though much smaller – trial involving methotrexate and placebo from nearly 30 years ago. Thirty-seven patients participated in that 1984 study, which was published in Arthritis & Rheumatism. It found improved physician assessments of arthritis (and in the amount of skin surface affected by psoriasis) but nothing else.
As for this study, Dr. Rubin asks, “Is it going to change most clinically practicing rheumatologists treatment of people with psoriatic arthritis? No. Is it intriguing? Yes. Does it mean there may be better drugs for the disease? Probably yes.”
Dr. Matteson agrees. “I do think that anti-TNF [tumor necrosis factor] agents are the best choice especially for patients with multiple involved joints,” Dr. Matteson says, referring to biologic agents such as etanercept, or Enbrel, infliximab, or Remicade, and adalimumab, or Humira. “[But] it is important to recognize that psoriatic arthritis is a spectrum of very mild to very severe disease, and that there are patients who do not require biologics for management of their disease.”
It’s also important to note, as the study authors did, that British medical authorities recommend using methotrexate before moving on to more expensive, anti-TNF therapies. In the United States, the American College of Rheumatology recommends that treatment of PsA be related to the severity of the condition and the level of pain. Nonsteroidal anti-inflammatory drugs, such as ibuprofen or naproxen; traditional disease-modifying antirheumatic drugs including methotrexate, leflunomide and sulfasalazine; and anti-TNFs are all deemed appropriate.
Dr. Rubin suspects that, given the length of time it took to set up the study, the researchers may have had some trouble recruiting patients for ethical reasons. “This was an almost 10-year project for a six-month study,” Rubin says. “There are a lot of physicians who probably said, ‘I don’t know whether it’s ethical to put a patient with psoriatic arthritis on placebo for six months.’”