Some Psoriasis Biologics Better Than Others for Preventing Progression to PsA

Psoriasis was less likely to progress to psoriatic arthritis (PsA) among patients treated with interleukin-17 (IL-17) or IL-23 inhibitors compared with those receiving tumor necrosis factor (TNF) inhibitors, a single-center study from Italy found.

PsA developed in 14.2% of 317 patients on anti-TNF agents, compared with 5.5% of 164 given IL-17 inhibitors and 4.3% of 141 receiving IL-23 blockers, according to Paolo Gisondi, MD, of the University of Verona, and colleagues.

With statistical adjustments meant to account for possible confounding factors, these rates translated to hazard ratios for PsA development of 0.63 for IL-17 inhibitors (95% CI 0.38-1.05) and 0.57 for IL-23 inhibitors (95% CI 0.34-0.96) relative to anti-TNF drugs, the researchers reported in Annals of the Rheumatic Diseases.

But Gisondi and colleagues were cautious about putting their findings front and center in clinical practice. “[T]he choice of the biological treatment should not be based on some hypothetical benefit of a lower risk of PsA,” they wrote. “Additional investigations on IL-23 inhibitors, which might be effective on pathogenic or regulatory T cells, should be conducted. Prospective observational cohorts with disease activity measures and pragmatic randomized trials with active comparators are needed to fill the gap in knowledge on this issue.”

Whether targeted agents differ in their ability to prevent psoriasis progression to PsA is an important question. Something like one-quarter of psoriasis cases eventually become psoriatic arthritis, Gisondi’s group noted; one recent guideline put the risk at “up to a third.” In general, patients on biologic drugs show less risk for progression compared with those treated with topical products or phototherapy. Some previous studies using insurance claims have suggested that TNF inhibitors aren’t as effective as newer targeted agents for preventing PsA development, but these were hampered by the limitations inherent in such records, which typically have scant baseline information on patients.

As an initial step, Gisondi and colleagues examined the substantially more detailed clinical records for 622 psoriasis patients started on TNF, IL-17, or IL-23 inhibitors at the University of Verona’s outpatient clinic from January 2012 to June 2023. Of these, just over half were on anti-TNF agents while therapy for the rest was about equally divided between the IL-17 and IL-23 inhibitors. Other eligibility criteria included lack of previous biologic therapy and continuous use of the prescribed drugs for at least 6 months.

TNF inhibitors used in these patients included etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), and certolizumab pegol (Cimzia). IL-17 inhibitors included secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). In the IL-23 inhibitor class were guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi), as well as the dual IL-12/23 inhibitor ustekinumab (Stelara). Gisondi and colleagues didn’t attempt to stratify findings by these individual products, but nearly 70% of the TNF inhibitor group got adalimumab. No particular drugs were predominant in the IL-17 and IL-23 inhibitor classes.

With mean follow-up of 4.1 years (SD 2.1), 10% of patients overall developed PsA. (Mean follow-up was shorter, at about 3 years, for IL-17 and IL-23 inhibitors, than the 4.5 years for patients receiving anti-TNF agents, the authors noted.) Just over half of the PsA cases were of the oligoarthritis type; one-quarter showed primarily enthesitis and the rest showed dactylitis.

Patients in the three treatment groups differed considerably at baseline — particularly by age, presence of skin fold psoriasis, body mass index, and psoriasis severity, Gisondi and colleagues pointed out, which could have influenced decisions as to which drugs to use. Therefore, they employed “inverse probability of treatment” weighting to adjust for these and other factors. This “greatly improved” the balance among the three groups, the researchers indicated. The resulting hazard ratios confirmed the unadjusted results, showing a numerical advantage for IL-17 inhibitors and a statistically significant one for IL-23 inhibitors, both relative to TNF inhibitor therapy.

Results were similar in a sensitivity analysis restricted to patients starting treatment in 2016 or later, when IL-17 and IL-23 inhibitors were more widely available than previously. In this set, involving 260 on anti-TNF drugs, 158 on IL-17 inhibitors, and 138 on IL-23 inhibitors, the hazard ratios for the latter two classes (0.52 and 0.42, respectively) relative to the first were both statistically significant.

Gisondi and colleagues acknowledged a number of limitations to their study, beyond its single-center and non-randomized nature. PsA diagnoses were made by an “expert rheumatologist,” but this clinician was aware of patients’ treatment assignments. As well, inverse probability of treatment weighting doesn’t necessarily account for all potential confounders. Finally, the study didn’t address the treatments’ effectiveness for relieving psoriasis symptoms, the number one goal of therapy.

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