Guselkumab bests fumaric acid esters for psoriasis

Key takeaways:

• Patients treated with guselkumab vs. fumaric acid esters experienced greater improvement in PASI scores.
• When switched from fumaric acid esters to guselkumab, many patients experienced marked improvement.

Patients with plaque psoriasis experienced greater efficacy with guselkumab compared with fumaric acid esters, according to a study.

“Fumaric acid esters (FAE) have been used as a treatment for psoriasis since 1959, and remain a commonly prescribed first-line systemic therapy in Germany. Their effect is likely attributed to immunomodulatory, anti-inflammatory and anti-oxidative actions,” Diamant Thai, MD, of the Institute and Comprehensive Centre for Inflammation Medicine at the University of Lübeck, and colleagues wrote. “Recent advances in understanding of pathophysiology suggest that several cytokines (eg, interleukin [IL]-17, IL-22, IL-23, IL-36, interferons and tumor necrosis factor [TNF]-alpha) play a major role in psoriasis pathogenesis.”

Guselkumab, a monoclonal antibody that targets IL-23p19, has been approved in Europe and the United States for the treatment of moderate to severe plaque psoriasis.

In the POLARIS study, patients were randomly assigned to receive 100 mg subcutaneous injection of guselkumab at weeks 0 and 4 and then every 8 weeks, or oral FAE through 24 weeks. Following this first part of the study, patients could enter part 2 if they completed phase 1, and could furthermore enter phase 3 if they received guselkumab in part 2, achieved PASI 90 at week 56 and had no baseline psoriatic arthritis.

Patients continued on their original treatment plan through week 32 in phase 2a. For phase 2b, which ran from weeks 32 through 64, patients with PASI 75 response at week 32 continued their treatments, whereas nonresponders were switched to only receive guselkumab regardless of initial treatment assignment. Phase 3 patients included patients who achieved PASI 90 at week 56 and were withdrawn from treatment and followed until the end of the study or loss of response.

Following the study’s part 1, all 56 patients in the guselkumab group and 35 of the 36 in the FAE group entered phase 2a.

At week 32, PASI 90 was reached by 78.3% of the guselkumab group compared with 11.9% of the FAE group (P < .001), and PASI 75 was reached by 90% and 23.7% of the two cohorts, respectively (P < .001). Also at this time point, a DLQI score of 0/1 was achieved by 63.3% of those treated with guselkumab compared with 16.9% of those treated with FAE (P < .001).

At week 56, 90.7% of the guselkumab arm and 50% of the FAE group who had each stayed with their original treatments reached PASI 90 (P = .002), and 98.1% and 64.3% reached PASI 75 (P < .001).

Those who were switched from FAE to guselkumab and those who remained on guselkumab constantly had higher improvement rates in PASI, DLQI and IGA.

“Treatment with guselkumab showed higher efficacy and a more tolerable safety profile compared with FAE in patients with moderate to severe psoriasis,” the authors wrote. “In these exploratory analyses, guselkumab, as a first-line systemic treatment or second-line systemic treatment in FAE nonresponders, was associated with long-term maintenance of responses, even after treatment withdrawal, and a favorable safety profile.”