Psoriatic Arthritis: Updated Guideline Clarifies Treatment Sequence

Clinicians looking for a fresh and authoritative guide to drug treatment for psoriatic arthritis (PsA) can thank the European Alliance of Associations for Rheumatology (EULAR), which just published an updated recommendation document.

Covering the full range of available disease-modifying anti-rheumatic drugs (DMARDs) -- including conventional, biologic, and targeted oral agents -- the new guideline comes with an easy-to-follow algorithm, in words and with a graphical flow diagram, for which drugs to start or add and under what circumstances.

Led by Laure Gossec, MD, PhD, of INSERM and Sorbonne Université in Paris, the guideline appeared in Annals of the Rheumatic Diseases.

"Since the last EULAR recommendations for the pharmacological management of PsA in 2019, the field has changed significantly," Gossec and colleagues explained, with the research that went into that iteration completed even earlier. Numbers of drugs originally approved for rheumatoid arthritis or plaque psoriasis have since gained PsA indications. Also, the landmark ORAL Surveillance trial that examined the safety of Janus-associated kinase (JAK) inhibitors was completed in 2020, with the major findings published in 2022.

"An update of the EULAR PsA management recommendations was therefore timely," the researchers wrote.

A total of 18 drugs are covered in the new document, including three conventional DMARDs (methotrexate, sulfasalazine, and leflunomide), five tumor necrosis factor (TNF) blockers, six inhibitors of various interleukin (IL) species, the CTLA-4 inhibitor abatacept (Orencia), two JAK inhibitors, and the phosphodiesterase-4 inhibitor apremilast (Otezla). These are the products carrying approved PsA indications as of December 2023.

The update begins by outlining the recommended principles and goals of care. These include maximizing patients' health-related quality of life; making treatment decisions in concert with the patient; and setting a clinical target for drug treatment to achieve, such as remission or low disease activity. Patients should be monitored regularly to determine if the pre-established goal is being met and for adverse effects.

Many of these appeared in the previous guideline, but the update alters the wording substantially for many and adds two new ones: safety considerations should take into account the drugs' mechanism of action (presumably in light of the ORAL Surveillance findings) and, in thinking about mechanisms of action, clinicians should consider the effects on non-musculoskeletal symptoms.

This latter point means that "with clinically relevant skin manifestations, preference should be given to an IL-17A or IL-17A/F or IL-23 or IL-12/23 inhibitor; with uveitis to an anti-TNF monoclonal antibody; and with [inflammatory bowel disease] to an anti-TNF monoclonal antibody or an IL-23 or IL-12/23 or a JAK [inhibitor]."

In general, according to the guideline's algorithm, drug therapy should start with a conventional DMARD; if patients have shown improvement after 3 months and achieved the prespecified clinical target at 6 months, no further changes in treatment are needed. But if both are not met, then a biologic or targeted agent (depending on the specific manifestations, as noted above) should be added.

The same evaluations should be performed after 3 and 6 months; again, if improvement is seen and the target is met, then patients may continue on that regimen. Failure at this stage means more adjustments are needed, which can be switching to a different drug in the same class or to a different class altogether.

These recommendations drew broad support from the 36-member guideline committee, which included just about every big European name in rheumatology, and most were strong with backing from high-quality evidence (grade 1 on standard scales). But the group acknowledged that many clinical questions don't yet have solid answers, and they listed several dozen to be addressed in future research. Some of these included:

• How rheumatologists should fit with other specialists in managing PsA patients
• Defining and treating early and pre-PsA
• Improving PsA prognosis
• Use of biosimilars, especially as a first DMARD choice
• Better outcome measures
• Improving pain and fatigue treatment
• Managing comorbidities
• Optimizing drug switches

Cost is also a consideration in drug choice, the new guideline emphasizes. "[I]t is generally recommended to prescribe the cheaper drug if two agents have similar efficacy and safety. Of note, even if one mode of action may have somewhat better efficacy on certain manifestations, a less expensive agent could still be preferred as long as it does not bear much lesser efficacy in that disease domain," Gossec and colleagues wrote.

They also expressed the hope that, as more current drugs go off patent and become available as generics or biosimilars, that too will bring down treatment costs and bring more patients into therapy.

In a few years, "[a]s new data become available and new drugs are authorized in PsA," further updates can be expected, they added.

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