A matching-adjusted indirect comparison (MAIC) of clinical trial data suggests that difamilast 1% cream demonstrates comparable efficacy and safety to delgocitinib in the treatment of moderate-to-severe atopic dermatitis (AD). The study, published in SpringerMedizin, addresses the lack of head-to-head trials comparing the two drugs, both approved for AD treatment in Japan.
The analysis used data from a Phase 3 trial of difamilast and two studies of delgocitinib. To account for differences in baseline characteristics between the trial populations, a MAIC methodology was employed. This approach statistically adjusts patient-level data from the difamilast trial to match the aggregate data from the delgocitinib studies, reducing bias in the indirect comparison.
MAIC Methodology
The MAIC analysis considered several baseline characteristics, including age, sex, body mass index (BMI), duration of AD, baseline Investigator's Global Assessment (IGA) scores, baseline modified Eczema Area and Severity Index (mEASI) scores, history of prior treatment, and percentage of body surface area (BSA) affected. Individual patient data from the difamilast trial were weighted to align with the baseline characteristics of patients in the delgocitinib trials who had a baseline IGA score of 3 or 4 (moderate or severe AD).
Efficacy and Safety Outcomes
The primary outcome was the proportion of patients with AD by severity stage as defined by the EASI score at week 4. Secondary outcomes included the mean percent change from baseline to week 4 in mEASI score, the proportion of patients achieving mEASI-50 or mEASI-75 at week 4, and the percentage of patients experiencing any adverse events (AEs) from baseline to week 4.
The results showed no statistically significant differences between difamilast and delgocitinib in the proportion of patients achieving EASI-50 or EASI-75 at week 4. Similarly, there were no significant differences in the incidence of adverse events between the two treatment groups. According to the study, difamilast exhibited a nearly similar mean percentage improvement in mEASI at week 4, mEASI-50 and mEASI-75 to delgocitinib.
Context of Atopic Dermatitis Treatment
Atopic dermatitis is a chronic inflammatory skin condition affecting millions worldwide. Current management approaches include topical corticosteroids, topical calcineurin inhibitors like tacrolimus, and Janus kinase (JAK) inhibitors like delgocitinib. Difamilast, a selective phosphodiesterase-4 (PDE4) inhibitor, offers an alternative mechanism of action. The study suggests that difamilast is comparable in clinical efficacy and safety with delgocitinib.
Study Limitations
The authors noted several limitations, including a reduction in the effective sample size (ESS) in the difamilast group after MAIC, which may have compromised the statistical power of the analysis. They also acknowledged the potential for bias due to unobserved effect modifiers or prognostic factors not accounted for in the analysis. The authors emphasize the importance of conducting direct comparison studies to further validate these findings.
"Due to the above limitations, even though the MAIC method allowed for an indirect comparison of difamilast and delgocitinib studies within an equivalent population, the patients qualified for difamilast were different from those treated with delgocitinib. This underscores the importance of conducting direct comparison studies," the researchers stated.
