TNF Inhibitor Plus Methotrexate Surpassed Monotherapy in PsA

Mitchel L. Zoler, PhD

June 10, 2020

Adding a tumor necrosis factor inhibitor to the treatment regimen of patients with psoriatic arthritis who failed to reach minimal disease activity on methotrexate monotherapy after 4 or more weeks had more than triple the rate of minimal disease activity after 16 weeks, compared with patients who had their methotrexate dosage escalated but received no second drug, in a multicenter, randomized study with 245 patients.

After 16 weeks, 42% of 123 patients with psoriatic arthritis (PsA) treated with methotrexate and the tumor necrosis factor (TNF) inhibitor adalimumab achieved minimal disease activity, compared with 13% of 122 patients randomized to receive escalated methotrexate monotherapy to their maximally tolerated dosage or to a maximum of 25 mg/week, Laura C. Coates, MBChB, PhD, reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The findings are "supportive of the EULAR recommendations" for managing patients with PsA, said Dr. Coates, a rheumatologist at the University of Oxford (England). The EULAR recommendations call for starting a biologic disease-modifying antirheumatic drug (bDMARD) in patients with PsA and peripheral arthritis and "inadequate response to at least one [conventional synthetic] DMARD," such as methotrexate (Ann Rheum Dis. 2019 Jun;79[6]:700-12). "A proportion of patients treated with methotrexate do well, but for those struggling on methotrexate, these results support use of a TNF inhibitor. It's a balance of cost and benefit. If TNF inhibitors were as cheap as methotrexate, I suspect that would be first line more frequently," Dr. Coates said in an interview. In contrast, the PsA management recommendations from the American College of Rheumatology make treatment with a TNF inhibitor first line, before starting with what these guidelines call an oral small molecule, the same as a conventional synthetic DMARD such as methotrexate (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

"It's a well-known fact that adalimumab is more effective than methotrexate in [PsA] patients who do not respond sufficiently well to methotrexate. Patients failing on methotrexate have been escalated to a TNF inhibitor for years," commented Robert B.M. Landewé, MD, a rheumatologist and professor of medicine at the University of Amsterdam, and a coauthor of the EULAR PsA treatment recommendations. "In the Netherlands and in my practice, every [PsA] patient starts on methotrexate until a dosage of at least 15 mg/week, but if they don't have sufficient response we escalate to adding a TNF inhibitor," he said in an interview. "A significant proportion of patients with PsA respond well to moderate to higher dosages of methotrexate," and this monotherapy with escalation of methotrexate can be safely continued for more than 3 months in many patients without the risk of "losing too much time by waiting" to start a bDMARD.

Dr. Coates said that her practice was to look for some level of response to methotrexate by 12 weeks on treatment and for achievement of minimal disease activity within 24 weeks of treatment. If these targets are not reached, she then adds a TNF inhibitor.

The CONTROL study ran at 60 sites in the United States and in 12 other countries and enrolled patients with active PsA despite treatment with methotrexate for at least 4 weeks and no history of treatment with a bDMARD. Patients received either 40 mg adalimumab every other week plus 15 mg of methotrexate weekly, or maximum-tolerated methotrexate up to 25 mg/week. The results also showed that the primary endpoint of the rate of achieved minimal disease activity seen overall in each of the two study arms was consistent in both the roughly half of patients who had been on methotrexate monotherapy for 3 months or less before entering the study as well as those who had been on initial methotrexate monotherapy for a longer period. Other secondary endpoints examined also showed significantly better responses to adding adalimumab, including a tripling of the rate at which patients achieved complete resolution of their Psoriasis Area and Severity Index score, which occurred in 30% of patients on the TNF inhibitor plus methotrexate and in 9% of those on methotrexate monotherapy.

The results seen in the CONTROL study with adalimumab would likely be similar using a different TNF inhibitor or an agent that's an adalimumab biosimilar, Dr. Coates said. The only patients with PsA and not achieving minimal disease activity on methotrexate monotherapy who should not then receive add-on treatment with a TNF inhibitor are those known to have a safety exclusion for this drug class or patients for whom the incremental cost poses a barrier, she added. In addition, patients with more substantial skin involvement may get greater benefit from a different class of bDMARD, such as a drug that inhibits interleukin-17 or IL-12 and -23 as recommended by the EULAR panel.

"We still get very good results with a TNF inhibitor for psoriasis, but in patients with severe psoriasis there is an argument to use a different drug," Dr. Coates acknowledged. Skin responses with an IL-17 inhibitor or an IL-12/23 inhibitor "are far better" than with a TNF inhibitor, said Dr. Landewé. He also added the caution that longer-term use of adalimumab "may induce aggravation of PsA in a significant number of patients."

CONTROL was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Coates has been a consultant to AbbVie, as well as to Amgen, Biogen, Boehringer Ingelheim, Celgene, Jansen, Novartis, Pfizer, and UCB. Dr. Landewé has been a consultant to AbbVie, as well as to Eli Lilly, Novartis, Pfizer, and UCB.

European League Against Rheumatism (EULAR) 2020 Congress: Abstract OP0050.

This article originally appeared on MDEdge.com.

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