Psoriatic Arthritis: What Role for Methotrexate?



Treatment of early psoriatic arthritis with etanercept (Enbrel) was more effective than treatment with methotrexate, whether the biologic was used as monotherapy or in combination with methotrexate, a randomized phase III trial found.

At week 24, 60.9% of patients on etanercept monotherapy had achieved a 20% improvement in their joint symptoms according to the criteria of the American College of Rheumatology (ACR20), compared with 50.7% of those receiving methotrexate monotherapy (P=0.029), according to Philip J. Mease, MD, of the University of Washington in Seattle, and colleagues.

And among patients randomized to receive both etanercept and methotrexate, ACR20 responses at week 24 were observed in 65% compared with 50.7% of those on methotrexate monotherapy (P=0.005), the investigators reported online in Arthritis & Rheumatology.

"Unlike in rheumatoid arthritis, it appears that the combination of methotrexate with etanercept does not confer an advantage over etanercept alone in most clinical situations with psoriatic arthritis," commented Shreyasee Amin, MD, of the Mayo Clinic in Rochester, Minn., who was not involved in the study.

"The exception seems to be in those with more significant involvement of psoriasis where combination therapy may have an advantage in controlling the skin disease," Amin told MedPage Today.

For example, among patients whose baseline psoriasis involvement was 10% or more of body surface area, the improvement in skin disease at 24 weeks was 65.7% in the methotrexate monotherapy group compared with 74.2% in the etanercept monotherapy group, which was not a significant difference, but was 81.6% in the combination group (P<0.001). For that subgroup, skin status at week 24 was considered clear or almost clear in 59.3% of the methotrexate monotherapy group, in 79.1% of the etanercept monotherapy group, and in 78.8% of the combination group.

Methotrexate is approved for use in psoriasis, but not for psoriatic arthritis. Nonetheless, it is widely used, and previous studies have had limitations and have demonstrated mixed results. In one randomized trial that compared methotrexate with placebo, no significant differences were seen at 6 months, but the study had a high dropout rate and used a suboptimal (15 mg/week) dosage of methotrexate.

In rheumatoid arthritis, clear benefit has been demonstrated for combining a TNF inhibitor with methotrexate, such as in the double-blind TEMPO trial. However, there has not been a similar trial in psoriatic arthritis, and observational studies have shown little benefit for the combination.

Therefore, to examine the effects of TNF inhibition versus methotrexate and combination therapy in a large study with optimal methotrexate dosing, Mease and colleagues enrolled 851 patients from 124 centers in 17 countries. Participants had not previously used biologic therapies, and could have received methotrexate for psoriasis but not for psoriatic arthritis. Enrollment took place from 2015 to 2018.

Patients were randomized to receive subcutaneous etanercept, 50 mg/week, methotrexate in target dosages of 20 mg/week, or both. At week 24, those with an inadequate response could receive rescue therapy with the combination through week 48.

Participants' mean age was 48, most were white, and the sexes were equally represented. Mean duration of psoriatic arthritis was slightly over 3 years, but for more than half of the patients the disease duration was less than 2 years. Mean swollen and tender joint counts were 12 and 20, respectively, and mean body surface area involved was 11%.

A key secondary endpoint, minimal disease activity at week 24, was achieved by 35.9% of the etanercept group compared with 22.9% of the methotrexate group (P=0.005). This endpoint also was reached by 35.7% of the combination group versus 22.9% of the methotrexate group (P=0.005).

Similar results were seen for other joint manifestations. The percentages of patients achieving ACR50 responses were 44.4%, 30.6%, and 45.7% for the etanercept monotherapy, methotrexate monotherapy, and combination groups, respectively, while for ACR70 responses, the numbers were 29.2%, 13.8%, and 27.7%.

"Though not formally tested for comparison, the ACR and minimal disease activity responses for the combination therapy and etanercept monotherapy arms were similar," the investigators observed.

Radiographic changes at week 48 were assessed with the modified total Sharp score. Changes on that score were -0.04 for etanercept alone compared with 0.08 for methotrexate (P=0.014) and -0.01 for the combination versus 0.08 for methotrexate alone (P=0.041).

In all three groups, similar improvements were seen at week 24 on the Health Assessment Questionnaire Disability Index.

Rates of most adverse events were similar in the three groups, although nausea was reported more often with methotrexate, in 13.1% of the methotrexate monotherapy group and in 14.4% of the combination group compared with 6.4% of the etanercept monotherapy group.

"This is an important study that provides practical, clinically relevant information for clinicians regarding the management of patients with psoriatic arthritis," Amin stated.

"For individuals who have a contraindication to methotrexate, there at least does not appear to be any significant disadvantage to using etanercept alone without methotrexate for managing psoriatic arthritis," he said.

A limitation of the study was its lack of a placebo control group.

The study was funded by Amgen.

The authors reported financial relationships with Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Sun, UCB, AbbVie, Janssen, Eli Lilly, Novartis, Pfizer, and Gilead. Several are employees of Amgen.

Source: https://www.medpagetoday.com/rheumatology/arthritis/78065

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