Dermatology

Lutikizumab benefits anti-TNF–refractory moderate–severe HS, especially at higher, more frequent dosing

Adults with moderate to severe hidradenitis suppurativa and prior anti-TNF failure were randomized to three lutikizumab regimens versus placebo for 16 weeks. HiSCR50 at week 16 was higher with lutikizumab 300 mg weekly (48.7%) and 300 mg every other week (59.5%) than placebo (35.0%). Bayesian analysis suggested high posterior probabilities of benefit for 300 mg every other week and weekly, but not for 100 mg every other week. Secondary endpoints, including pain, draining tunnels, and quality of life, generally favored higher-dose lutikizumab regimens. Safety over 16 weeks appeared acceptable with no major new signals, though follow-up was limited to a 9-week safety period. 1

Intralesional IL-2 yields high complete responses in high-risk or nonsurgical cSCC

Sixteen patients with high-risk, recurrent, or cosmetically sensitive cutaneous squamous cell carcinoma received biweekly intralesional IL-2 at a specialized referral center. Patients were poor surgical candidates or attempted intralesional therapy to avoid morbid procedures on sensitive sites. Treatment achieved an 81% complete response rate and a mean progression-free survival of 19 months. Adverse events were limited to grade 1–2 toxicities in this elderly cohort, supporting favorable tolerability. These results support intralesional IL-2 as a low-cost, organ-sparing option for carefully selected high-risk or nonsurgical cSCC patients. 2

JAK inhibitors in skin IMIDs show no excess boxed-warning events versus methotrexate or cyclosporine

This multinational cohort compared JAK inhibitors with methotrexate or cyclosporine in 17,068 propensity-matched patients with psoriatic disease, atopic dermatitis, or alopecia areata. Over two years, JAK inhibitor users had lower all-cause mortality and major adverse cardiovascular events than conventional immunomodulator users. Risks of venous thromboembolism and malignancy were not increased with JAK inhibitors versus methotrexate or cyclosporine. Subgroup analyses in older patients and those with cardiometabolic risk factors showed no new safety signal. These data suggest that, in dermatologic populations, JAK inhibitor boxed-warning events are not more frequent than with traditional systemic agents. 3

Planned withdrawal of IL inhibitors in psoriasis markedly increases relapse without safety gain

This systematic review and network meta-analysis pooled 18 randomized trials including 2995 psoriasis patients undergoing planned IL inhibitor withdrawal versus maintenance. Across agents, withdrawal was associated with substantially higher relapse risk compared with continuous treatment, while adverse event rates were similar. For PASI90 maintenance, bimekizumab withdrawal showed a lower relapse risk than ixekizumab withdrawal and a risk comparable to guselkumab. There was no evidence that limited-time withdrawal reduced adverse events versus ongoing IL blockade. These findings argue against routine drug holidays for IL inhibitors when psoriasis is well controlled, particularly for ixekizumab. 4