Abstract
Objective To evaluate the long-term safety and efficacy of dazukibart, a novel antiinterferon β monoclonal antibody, in adults with moderate-to-severe dermatomyositis (DM).
Methods Participants from 2 cohorts of DM (skin-predominant [SP] and muscle-predominant [MP]) completing a 24-week phase II, double-blind study, were enrolled into a 52-week phase IIb, open-label extension (OLE) study, with a 16-week follow-up post treatment (combined study duration: 92 weeks). The pooled skin analysis set included all SP and MP DM participants with baseline Cutaneous Dermatomyositis Disease Area and Severity Index–Activity (CDASI-A) scores ≥ 14. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs) from week 24 through week 92. Key secondary endpoints were change in CDASI-A and Total Improvement Score (TIS) from week 0 through week 92.
Results Participants who received ≥ 1 dose of dazukibart (600 mg) during the OLE study (comprising 9, 15, and 16 participants from the SP cohort, MP cohort, and pooled skin analysis set, respectively) were analyzed (median age 49.5 years, 83% female, 96% White). TEAEs were mild (55%), moderate (38%), or severe (7%), with no treatment-related serious AEs or treatment discontinuations. At week 76, CDASI-A scores improved, with a median change from baseline of −24.0 (range −33 to −12), −9.0 (range −32 to 1), and −23.5 (range −33 to −12) for participants from the SP cohort, MP cohort, and pooled skin analysis set, respectively. In the MP cohort, TIS (median 65.0, range 2.5-95.0) and associated core set measures, including patient-reported outcomes, improved at week 76. Overall, the observed improvements in outcomes, as indicated by the slight reduction in outcome measures, persisted during the 16-week posttreatment follow-up.
Conclusion The safety and efficacy profiles of dazukibart observed at 24 weeks were sustained through 92 weeks. (ClinicalTrials.gov: NCT03181893, NCT05192200)
Plain Language Summary
Dermatomyositis is a rare disease that causes skin rashes and muscle weakness. It may also affect the joints, lungs, heart, and digestive system. Since patients experience variable improvement with currently available treatment options, more effective treatment is needed. We studied a drug called dazukibart, which targets an important regulator of immune response in adults with dermatomyositis. Combined results are reported from 2 studies. The first was a previous 24-week double-blind (both participants and investigators were unaware of the treatment given to the participants) study in which patients were randomly allocated to either placebo or different doses of dazukibart. The second was a 52-week open-label extension (both participants and investigators were aware of the treatment given to the participants) in which all patients received the same dose of dazukibart. There was also a 16-week follow-up after the end of treatment, for a total study duration of 92 weeks. During the double-blind study, improvement in dermatomyositis was observed with dazukibart treatment. From this study, some patients with predominant skin disease (the skin-predominant cohort) or predominant muscle disease (the muscle-predominant cohort) continued into the open-label extension study. Patients from the skin and muscle cohorts with more severe skin disease were also assessed, forming the pooled skin analysis set. Improvement in dermatomyositis was measured using skin disease activity scores for skin symptoms and a total disease activity score for muscle and overall symptoms. Overall, treatment with dazukibart was safe, with mainly mild side effects. Patients who continued to the open-label extension study experienced a sustained improvement in both skin and total disease activity scores over 92 weeks. Dazukibart may be a potential treatment option for dermatomyositis, although more studies within larger patient groups are needed.
