Dr Lebwohl expounded upon a common clinical question: how to choose a treatment regimen for patients with psoriasis in a world with dozens of biologics and small-molecule inhibitors. In addition to considering pertinent medical history like inflammatory bowel disease or concomitant autoimmune disorders, Dr Lebwohl looks for biologic medications with evidence to mitigate or prevent psoriatic arthritis. He presented data from numerous randomized trials that showed promising results from various TNF-alpha inhibitors and biologics alike. Etanercept inhibited structural damage of joints compared to placebo based on no change from baseline of the Sharp, or van der Heijde, score in one trial, and 45% to 58% of those on secukinumab demonstrated a 20% improvement in ACR, depending on previous TNF-inhibitor exposure, compared to 15% who were on placebo. Ustekinumab, ixekizumab, and bimekizumab demonstrated similar, if not superior, responses, suggesting that IL-17, IL-23, and IL-12/23 inhibitors share this effect. Bimekizumab in particular achieved an ACR20 in 62% of people compared to 68% on adalimumab at week 24. Guselkumab dosed every 4 weeks demonstrated significant improvement in Sharp, or van der Heijde, score, though every 8 weeks did not reach significance. 

Dr Lebwohl then examined multiple trials looking at the other small-molecule inhibitors’ impact on psoriatic arthritis. He started with apremilast, the oral PDE4-inhibitor, which also showed moderate improvement in ACR scores at both doses at week 16. Known for their quick onset of action, the JAK inhibitor class also has shown benefit for psoriatic arthritis with 70% of upadacitinib users achieving ACR20 at week 12. Deucravacitinib, the TYK2 inhibitor, similarly decreased ACR scores in multiple RCTs. On the other hand, methotrexate has not been shown to prevent joint damage on x-ray. Dr Lebwohl also reported cyclosporine and acitretin as not effective in preventing joint disease. 

Another variable to consider in some patients, Dr Lebwohl showed us, is weight in obese patients who haven’t achieved adequate response to medications. One trial showed that response to ixekizumab was modified by weight with 75% of those <80 kg achieving a PASI90 compared to 61% of those >100 kg achieving the same response. The difference was even greater for those receiving every-4-week dosing. Response to adalimumab can also be stratified by body weight, interestingly including the placebo group in the CHAMPION trial. For both ixekizumab and secukinumab, the higher doses were more efficacious for patients >90 kg. It appears that almost all of the biologics have evidence for weight-stratified responses. More evidence is required to determine if the same is true for the JAK inhibitor class.