Combination Therapy May Prevent Secukinumab Switching in Psoriasis

Combination therapy may improve symptoms and avoid the need for drug switching in patients with psoriasis who experienced secondary drug failure with secukinumab, according to findings published in Pharmaceuticals.

Although several antipsoriatic systemic therapies are known to be safe and effective in the treatment of psoriasis, drug survival remains a significant issue, as the efficacy of these therapies has been shown to wane over time. In managing this issue, researchers note that dermatologists have 2 therapeutic options: switching or performing a combination therapy (rescue therapy) to save the drug that had decreased its efficacy.

With scarce data existing on the use of combination therapies in patients with psoriasis, they conducted a 52-week multicenter retrospective observational study to examine the use of combination/rescue therapy for those receiving secukinumab, a fully human monoclonal immunoglobulin G1/j isotype antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin (IL)-17A.

In the study, 40 subjects with plaque psoriasis who underwent a secondary loss of efficacy under secukinumab and started another concomitant systemic rescue therapy (ciclosporin, 11; methotrexate [MTX], 15; narrow-band ultraviolet-based therapy [NB-UVB], 7; apremilast, = 7), were recruited:

• Apremilast and MTX was prescribed for the entire period of the study, according to in-label dose; the combination therapy with apremilast was reserved for patients who failed a tumor necrosis factor (TNF)-alpha inhibitor and at least another inhibitor of the IL-17/23 pathway
• Cyclosporin (dose, 3.5 mg/kg/day) was administered for 3 months, stopped for 1 months, and then re-administered for 3 months
• NB-UVB sessions were delivered in 3 cycles of 12 sessions each, starting from a minimum of 0.20 joule and then increasing up to 1.50 joule for each session, according to phototype

The median age of the patient cohort was 44.5 years, with females undergoing combination therapy at an older age than males (47.5 vs 42.5 years; P < .05). At baseline, the mean (SD) score on the Psoriasis Area and Severity Index (PASI) was 15.5.

Following rescue/combination therapy initiation, improvements on the PASI and Dermatology Life Quality Index after 16 weeks varied, respectively, from 8 (7.0-9.0) and 13 (12.0-15.0) to 3 (2.8-4.0) and 3 (2.0-3.3), suggesting a significant improvement of daily functionality and quality of life.

Results were maintained at 52 weeks, with no adverse effects reported during the study. Differences were found when comparing apremilast with the other combination therapies (ciclosporin, P = .01; MTX, P = .005; NB-UVB, P = .01), which the researchers said justified its clinical preference for the treatment of patients with uncontrolled psoriatic arthritis and a scarce cutaneous involvement.

“Multifailure patients constantly grow, and dermatologists are facing this challenge with a limited number of therapeutically interesting pathways to block; in this intricate scenario, the conscious use of combination therapy is a valid and relatively inexpensive strategy to treat patients with psoriasis,” concluded the researchers. “Further studies should be performed to establish precise protocols of combination therapy and switching criteria.”

Reference

Damiani G, Odorici G, Pacifico A, et al. Secukinumab loss of efficacy is perfectly counteracted by the introduction of combination therapy (rescue therapy): data from a multicenter real-life study in a cohort of Italian psoriatic patients that avoided secukinumab switching. Pharmaceuticals (Basel). Published online January 14, 2022. doi:10.3390/ph15010095