ROME – Tumor necrosis factor inhibitors remain the mainstay of treatment for patients with psoriatic arthritis who don’t fully respond to treatment with a nonsteroidal anti-inflammatory drug and at least one conventional synthetic disease-modifying antirheumatic drug in newly updated treatment recommendations written by a task force of the European League Against Rheumatism.
The revised recommendations for psoriatic arthritis (PsA) replace what EULAR had last released in 2011 and published in 2012 (Ann. Rheum. Dis. 2012;71:4-12) and also add three new drug options not mentioned in the 2011 version that the panel now endorsed as alternatives to a tumor necrosis factor (TNF) inhibitor when a TNF inhibitor is not appropriate. The three additions are ustekinumab (Stelara), which acts by inhibiting interleukin- (IL-)12 and IL-23, secukinumab (Cosentyx), which acts by inhibiting IL-17, and apremilast (Otezla), which inhibits phosphodiesterase-4. Ustekinumab and secukinumab are considered biological disease-modifying antirheumatic drugs (bDMARDs), like the TNF inhibitors, while apremilast occupies a new classification niche as a targeted synthetic DMARD, said Dr. Laure Gossec, convener of the PsA treatment task force, at the European Congress of Rheumatology.
Mitchel L. Zoler/Frontline Medical News
Dr. Laure Gossec
Although ustekinumab, secukinumab, and apremilast all have a role to play in managing selected PsA patients, they all remain second line to TNF inhibitors, stressed Dr. Gossec, professor of rheumatology at Pierre and Marie Curie University in Paris. A TNF inhibitor is the first agent to turn to when treatment with an NSAID and a conventional synthetic DMARD fails to bring about remission or minimal disease activity essentially because of its much longer track record of safety and efficacy, she said. Specifically, TNF inhibitors have been studied long term and have demonstrated their safety in registries, they have not been surpassed for efficacy by any other agent using indirect comparisons, and now that biosimilar TNF inhibitors have entered the market they also could potentially offer a price advantage, compared with newer agents.
But for some patients, TNF inhibitors are not appropriate, such as a patient with certain comorbidities or a history of infections that would make a TNF inhibitor contraindicated, she said. For these patients, one of the other types of biologic DMARDS now available would be the top alternative. In other patients, a comorbidity profile or a history of infections might make any biologic DMARD contraindicated, in which case the targeted synthetic DMARD apremilast is an appropriate alternative, she said.
The revised recommendations contain several other new items:
• For patients with active enthesitis, dactylitis, or both and an insufficient response to an NSAID or local glucocorticoid injections, then a TNF inhibitor or alternatively an IL-12 and IL-23 inhibitor (currently ustekinumab) or an IL-17 inhibitor (currently secukinumab) may be considered. Conventional synthetic DMARDS are ineffective for these patients, while in contrast all of the biologic DMARDs are effective, but the TNF inhibitors have an edge because of greater experience with the class in this setting.
• For patients with predominantly axial disease that is active and insufficiently responsive to NSAID treatment, a biologic DMARD should be considered, specifically a TNF inhibitor. Conventional synthetic DMARDs also have no efficacy for these patients, and few data exist regarding the efficacy of IL-12 and IL-23 inhibitors or IL-17 inhibitors.
• When patients fail to respond adequately to one biologic DMARD, switching to another biologic DMARD should be considered. This could involve switching from one TNF inhibitor to another, as some evidence exists that this could be effective. Alternatively, it could involve switching to a IL-12 and IL-23 inhibitor, an IL-17 inhibitor, or possibly a targeted synthetic DMARD (currently apremilast). The task force did not endorse any particular order of these drugs when switching occurs.
Dr. Gossec has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Novartis, Pfizer, Roche, and UCB.
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