Switching to Guselkumab Safe After Ustekinumab Failure in Psoriasis

Patients with plaque psoriasis who had an inadequate response to ustekinumab can switch to guselkumab, according to study results published in Journal of the European Academy of Dermatology & Venerology.

Researchers conducted a retrospective, multicenter study using data collected between 2020 and 2022. Participants (N=233; mean age, 54.27 [SD, 13.25] years; 56.12% men) with chronic plaque psoriasis who did not respond to ustekinumab therapy were switched to guselkumab 100 mg at weeks 0 and 4 followed by every 8 weeks thereafter were evaluated for outcomes.

Ustekinumab failure was defined as a Psoriasis Area and Severity Index (PASI) score of at least 10 or PASI score of less than 10 plus involvement in the palms or soles, face or scalp, or nails and/or a Dermatology Life Quality Index (DLQI) score of at least 5.

Among the participants, 24.89% had obesity, the mean disease duration was 24.20 (SD, 13.40) years, 68.24% had difficult site involvement, 21.03% had psoriatic arthritis, 49.79% had cardiometabolic comorbidities, and 40.34% had exposure to at least 2 biologics.

At week 16, 76.29% of participants achieved a 75% improvement in PASI (PASI75), 46.78% achieved a 90% improvement in PASI (PASI90), 37.77% achieved a 100% improvement in PASI (PASI100), and 77.68% reached an absolute PASI score of 2 or less. The rates of achieving these outcomes continued to improve through weeks 52 and 104.

Stratified by patient characteristics, mean PASI scores at week 52 (P =.002), achieving a PASI score of 2 or less at weeks 16 (P <.001) and 52 (P <.001), and achieving PASI75 at week 52 (P =.002) depended on body mass index category.

Achieving PASI90 at week 16 (P <.001), PASI100 at week 16 (P =.001), and PASI75 at week 52 (P =.026) depended on the presence of lesions in difficult areas.

Achieving PASI75 at week 16 (P =.041) and a PASI score of 2 or less at weeks 16 (P =.025) and 52 (P =.022) depended on the presence of cardiometabolic diseases. Mean PASI at week 16 (P =.006), achieving PASI75 at week 16 (P =.015), and a PASI score of 2 or less at week 16 (P =.006) depended on the presence of psoriatic arthritis. Mean PASI at week 16 (P =.023) depended on the number of previous biologic exposures.

In the multivariate analysis, psoriatic arthritis was associated with a decreased likelihood of achieving PASI75 (odds ratio [OR], 0.39; P =.009) or a PASI score of 2 or less (OR, 0.34; P =.007) at week 16. Difficult-to-treat areas were associated with lower odds of achieving PASI90 at week 16 (OR, 0.38; P =.001).

Achieving a PASI score of 2 or less at week 16 was less likely to occur among those with normal weight (OR, 0.20; P =.001) or who were overweight (OR, 0.30; P =.008) compared with individuals who were underweight. Those with obesity were less likely to achieve PASI75 (OR, 0.20; P =.022) or a PASI score of 2 or less (OR, 0.03; P =.008) at week 52 compared with individuals who were overweight.

The rate of adverse events was low (3.86%). The most common events were injection-site reaction (1.29%) and headache (1.2%).

Limitations of the study include the amount of missing or incomplete data.

Researchers conclude, “Guselkumab was well tolerated, as no significant safety findings emerged after 2 years of therapy. Larger and longer prospective studies and retrospective analyses of patient databases are needed to further assess the effectiveness and safety of guselkumab in real-life bio-experienced patients.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.