Experts have updated EULAR’s recommendations for the pharmacological treatment of psoriatic arthritis, emphasising safety and a cautious approach to JAK inhibitor treatment.

Most of the recommendations in the prior version in 2019 have been “modified substantially” due to new modes of action and new data on existing drugs. The guideline now also contains a new algorithm for the treatment of PsA and completely new advice on taking non-musculoskeletal manifestations of the disease into account when deciding on appropriate therapy.

New for 2024, the guideline task force of 36 international experts (including Professor Peter Nash from Australia) merged prior recommendations on the use of NSAIDs and glucocorticoids, given that “both only serve to relieve symptoms in the short term”.

Oral glucocorticoids were not recommended for patients with PsA. However, local injections could be considered adjunctive therapy to disease-modifying antirheumatic drugs (DMARDs) to temporarily relieve symptoms and inflammation.

The vast majority of patients should not be treated with NSAIDs alone; only those with very mild peripheral disease or with predominant entheseal or axial disease can potentially benefit from NSAID monotherapy; the task force noted and stressed that even in these cases, treatment should be limited to around four weeks.

“On the other hand, for patients with predominant axial disease who experience significant improvement in clinical symptoms, continuous NSAID use may be proposed if needed to control symptoms, always taking the risks and benefits into account,” they added in a paper published in Annals of the Rheumatic Diseases (link here).

Elsewhere, the update recommends that in patients with peripheral arthritis, clinicians should rapidly initiate treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) – with methotrexate the preferred choice – in those with clinically relevant skin presentation.

In patients who fail to respond adequately, treatment with a biological disease-modifying antirheumatic drug (bDMARD) should be started, but there was no preference for bDMARD mode of action.

JAK inhibitor caution

The task force cited various reasons for backing bDMARDs over JAK inhibitors (JAKi) at this stage of the treatment pathway.

“JAKi is efficacious in PsA, but the task force decided that at present, the efficacy-safety balance, costs and long-term experience with many bDMARDs favour their recommendation over JAKi. Relevant comorbidities in many patients with PsA also favour bDMARD selection,” the experts noted.

However, they recommended that in patients with peripheral arthritis who have an inadequate response to at least one bDMARD or when bDMARD treatment is not suitable, a JAKi can be an option with careful consideration of patient safety.

“This recommendation elicited much debate,” the task force said. “On the one hand, since 2019, new data have accrued on JAKis in terms of efficacy, such as the publication of positive trials on upadacitinib in PsA. On the other hand, there is currently a worldwide cautionary statement issued by both the Food and Drug Administration and the European Medicines Agency restricting the use of JAKis in all diseases, including PsA, based on an increased risk of cardiovascular and malignancy events observed with tofacitinib in older patients with RA with cardiovascular risk factors”.

Current long-term data have not shown an increased cardiovascular or cancer risk from JAKi use in patients with PsA; however, as there are no randomised controlled trials similar to ORAL-Surveillance in PsA landscape, it was felt that the same precautions should be taken as for rheumatoid arthritis, “especially since various comorbidities important for the JAKi risk profile may be more prevalent in PsA than in RA (e.g., obesity and cardiovascular risk factors),” they noted.

“We considered that the efficacy–safety balance of JAKis did not justify putting JAKis on the same level as bDMARDs for order of choice (ie, proposing JAKis as usual treatment after insufficient response and/or intolerance to csDMARD treatment). Therefore, JAKis are proposed usually as second-line targeted therapies (or third-line DMARDs), the taskforce explained.

Further treatment considerations

Other recommendations included choosing bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors for patients with clinically relevant skin psoriasis, and completely new for 2024, that the choice of treatment mode of action should also reflect the non-musculoskeletal manifestations of PsA.

With clinically relevant skin involvement, preferred choices are IL-17A or IL-17A/F or IL-23 or IL-12/23 inhibitors; with uveitis an anti-TNF monoclonal antibody; and with IBD an anti-TNF monoclonal antibody or an IL-23i or IL-12/23i or a JAKi, according to the paper.

In general, the group added a new overarching principle that stating that choice of “treatment should take account of safety considerations regarding individual modes of action to optimise the benefit-risk profile”.

It was stressed that costs are also “an important aspect,” and as such, the task force emphasised that it is generally recommended that the cheaper drug be prescribed should there be a choice between agents with 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,” the group advised.

Click here to read the updated guidelines in full.