WCM 2024 Conference Highlights

Kicking off our first day of lectures in Miami, Dr Brad Glick reviewed his tips and tricks for treating challenging psoriasis, including when psoriasis ends up being something else entirely. In this case-based presentation, he reviewed therapies for unresponsive palmoplantar psoriasis, comorbidities that may impact treatment of plaque psoriasis and psoriatic arthritis, and a psoriasis look-a-like presenting as exfoliative dermatitis. In the first case, a 74-yo female with palmoplantar psoriatic disease who failed many biologic therapies including secukinumab, ustekinumab, and risankizumab was started on deucravacitinib with remarkable improvement in palms, soles, and scalp psoriasiform lesions. This novel TYK-2 inhibitor can be considered as an “add-on” therapy due to its complimentary mechanism of action to many other biologics and is a reminder that more challenging cases may require compound treatment regimens. In the second case, a former smoker with severe psoriasis, psoriatic arthritis, and a pertinent medical history of valvular heart disease, cerebral aneurysm, and obesity was walked through a variety of treatments with gradually improving responses. While more targeted therapies may have been partially contributing to this patient’s dramatic reduction in IGA, Dr Glick also proposed the importance of weight loss for obese patients with only moderate responses to treatment. Two articles that were cited examine the impact of bariatric surgery and weight loss in general on psoriatic disease. Another pearl in this case is to consider repeating positive QuantiFERON-TB Gold tests before removing patients from successful treatment regimens, as they may be false positives or laboratory errors. He ended with a case of severe exfoliative dermatitis unresponsive to many different therapies that, after review of an initial biopsy report by a second pathologist, was more consistent with pityriasis rubra pilaris. Islands of sparing were evident in clinical photos, and the patient responded to risankizumab and acitretin. In patients with exfoliative dermatitis, always test for scabies and take a detailed exposure history.

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.

While many medications exist for the treatment of psoriasis, Dr Armstrong focused this lecture on the new and emerging therapies for this condition. She started with newly approved nonsteroidal topical medications, tapinarof and roflumilast. Interestingly, the former is derived from a species of bacteria within a roundworm with prominent anti-inflammatory properties, and patients treated with the cream demonstrated marked response that was even maintained for 24 weeks after stopping application. Dr Armstrong next reviewed the mechanism of action of deucravacitinib, the TYK2 inhibitor, which modulates the IL-23/IL-17 axis by binding to the more unique regulatory domain of the TYK2 molecule. Patients who obtained PASI75 or PASI90 by week 52 maintained response through an extension study of 3 years, and patients don’t require laboratory monitoring unless they have known liver or lipid disease. Novel IL-23 and IL-17 inhibitors are also under investigation. Bimekizumab is the newest approved biologic for psoriasis and has demonstrated fast onset and high efficacy with almost 70% of patients achieving a PASI100 by week 16 with noted improvement by week 4. Oral candidiasis is a known adverse event to be prepared for in patients on bimekizumab. She concluded by reviewing generalized pustular psoriasis, which has its first approved treatment with spesolimab. However, another important discussion launched by Dr Armstrong in the discussion of biologic medications is the clarification of biosimilars. They are defined as having identical therapeutic amino acid sequences relative to the reference product and must demonstrate biosimilarity in 3 features: pharmacokinetics, pharmacodynamics, and immunogenicity. She noted, however, that creating consistent identical copies of a biologic is nearly impossible, and dissimilarities exist even from batch to batch within the same manufacturer. Differences in biosimilars may be accounted for in delivery device, product concentration, or citrate content.