EULAR keeps csDMARDs as top PsA drugs



– The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.

Dr. Laure Gossec, professor of rheumatology, Sorbonne University, Paris Mitchel L. Zoler/MDedge News

Dr. Laure Gossec

For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.

The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).

The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.

The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.

Dr. Philip J. Mease, rheumatologist at Sweidsh Medical Center, Seattle Mitchel L. Zoler/MDedge News

Dr. Philip J. Mease

“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.

In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.

The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.

Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”

Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”

Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.

When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.

Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.

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