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.
Dermatomyositis (DM) is a multisystem idiopathic inflammatory myopathy characterized by skin eruptions, muscle weakness, and systemic manifestations that can affect the joints, lungs, heart, and gastrointestinal tract.1 DM may present with skin symptoms only or skin symptoms with significant muscle involvement.2 Cutaneous manifestations such as Gottron papules, Gottron sign, and/or heliotrope rash are key clinical features of DM skin disease, whereas DM muscle inflammation is characterized by mild-to-severe weakness of symmetric proximal muscles.2,3 Both skin and muscle involvement have a significant effect on quality of life in patients with DM.2,4
Treatment for DM often involves broad immunosuppression that does not target underlying disease mechanisms.3 The initial treatment approach for DM typically consists of systemic corticosteroids,5 immunosuppressive agents, and/or intravenous immunoglobulins (IVIGs).6,7 Systemic corticosteroids are often combined with methotrexate, mycophenolate mofetil, or azathioprine, among others, for increased efficacy and lower corticosteroid dependence.3,5,8 Despite these treatment strategies, a substantial unmet need for therapeutic options targeting specific disease pathways exists in DM.5 The involvement of proinflammatory cytokines such as type I interferon (IFN) is identified as a hallmark of the autoimmune pathophysiology in DM.1,2,9 Previous studies have shown that elevated levels of IFN-β positively correlate with cutaneous and muscle disease activity in myositis, supporting the inhibition of IFN-β as a promising therapeutic strategy in patients with DM.9-11
Dazukibart is a highly selective humanized IgG1 neutralizing monoclonal antibody directed against soluble IFN-β. An acceptable safety, tolerability, and pharmacokinetic profile of dazukibart was observed in a phase I, first-in-human, multiple-ascending dose study (ClinicalTrials.gov: NCT02766621).12 Subsequently, the safety and efficacy of dazukibart (IV 150 mg and 600 mg) were demonstrated in a phase II study (NCT03181893). The primary outcome (change from baseline in Cutaneous Dermatomyositis Disease Area and Severity Index–Activity [CDASI-A]) after 12 weeks and safety after 24 weeks of treatment were evaluated in participants with moderate-to-severe skin-predominant (SP) DM and muscle-predominant (MP) DM.13 Here, we report the combined long-term safety and efficacy outcomes from a secondary analysis of the phase IIb open-label extension (OLE) study (NCT05192200) of dazukibart in adults with DM, who completed the double-blind study (NCT03181893) and continued with active treatment. Key outcomes from the double-blind study are presented, with a focus on the long-term durability of response in the OLE study in participants treated with dazukibart over an extended period of 52 weeks.
METHODS
Participants and study design. Following the 24-week double-blind study,13 this phase IIb OLE study (NCT05192200) evaluated the long-term safety and clinical efficacy of dazukibart in adult participants with active DM over a 52-week treatment period. The double-blind study was a randomized, placebo-controlled, multistage, multicenter phase II study in adults with moderate-to-severe DM13 consisting of 4 stages—stages I, II, IIa, and III—with only stage IIa and III participants continuing to the OLE phase. Participants from stages I and II completed the double-blind study treatment period before the OLE study became available for enrollment and were therefore not enrolled in the OLE study. For stages IIa and III, the double-blind study spanned 24 weeks, consisting of a 12-week treatment phase, followed by a treatment switch at week 12 to enable a greater proportion of participants to receive dazukibart in the study. After completing the treatment period in the double-blind study, these patients were further enrolled into the OLE study; the overall trial is referred to as the combined double-blind and OLE study. This includes the 24-week double-blind study (baseline to week 24), 52-week OLE study (week 24-76), and 16-week follow-up period (week 76-92; Figure 1A).
Study design and participant disposition for combined double-blind and open-label extension study. (A) Study design: a total of 75 participants were randomized in the double-blind study. Of the 30 eligible participants, 24 were enrolled into the OLE study. Blue arrows: day of dose; red arrows: phase completion. (B) Participant disposition: the SP DM cohort includes all participants with skin-predominant DM who were enrolled in stage IIa of the double-blind study and continued to OLE study; the MP DM cohort includes all participants with muscle-predominant DM who were enrolled in stage III of the double-blind study and continued to OLE study; the pooled skin analysis set includes all participants with a CDASI-A score ≥ 14 at baseline in stage IIa or III of the double-blind study and continued to OLE study. Of the 3 participants who discontinued, 2 participants did not proceed to the follow-up phase, whereas the third participant entered the follow-up phase but subsequently withdrew from the study (withdrawal by participant). Irrespective of discontinuation, all participants were included in the safety and efficacy analysis. CDASI-A: Cutaneous Dermatomyositis Disease Area and Severity Index–Activity; DM: dermatomyositis; MP: muscle-predominant; OLE: open-label extension; seq: sequence; SP: skin-predominant.
Eligibility criteria were described in detail previously.13 Participants (aged 18-80 years) included in stage IIa had SP DM, whereas stage III participants had MP DM. The key inclusion criteria for stage IIa participants (with SP DM) in the double-blind study included a CDASI-A score ≥ 14 and failure of ≥ 1 standard-of-care systemic treatment. Stage III participants (with MP DM) had to have refractory disease (defined as the failure of ≥ 2 adequate courses of an immunosuppressive or immunomodulatory agent). In addition, the participants were required to meet 1 of the following 2 criteria: (1) a manual muscle testing 8 (MMT-8) score ≤ 136 (out of a potential total of 150) and a physician global assessment (PGA) of myositis score ≥ 3 cm on a visual analog scale (VAS), or (2) the sum of PGA VAS, patient global assessment (PtGA), and extramuscular global assessment (EmGA) scores ≥ 10 cm (0-10 cm VAS scale for each).13 There was no minimum baseline CDASI-A score required for stage III participants (Figure 1A). Participants needed approval from their study doctor to continue active treatment, with no significant protocol deviations in the double-blind study for enrollment in the OLE study.
Participants who completed the treatment period in stage IIa (n = 14/16) and stage III (n = 16/18) of the double-blind study were eligible to enroll into the OLE study. In the OLE study, the full analysis set (participants who received ≥ 1 dose of dazukibart) included the SP DM cohort (eligible participants from stage IIa of the double-blind study who continued into the OLE; n = 9/14) and the MP DM cohort (eligible participants from stage III of the double-blind study who continued into the OLE; n = 15/16). Five participants from stage IIa did not elect to continue into the OLE study after completing the double-blind study. Otherwise, the eligible participants could choose to join the OLE study. Additionally, the pooled skin analysis set was defined, which included all participants in the full analysis set with a CDASI-A score ≥ 14 at baseline in the double-blind study (ie, all participants from the SP DM cohort and some from the MP DM cohort with baseline CDASI-A ≥ 14; n = 16). Although SP and MP are not formally recognized classification groups for DM, these naming conventions are used to describe the clinical characteristics of participants in each stage.13
Procedures and assessments. In the double-blind study, participants in the SP DM cohort received dazukibart 600 mg, dazukibart 150 mg, or placebo, and participants in the MP DM cohort received dazukibart 600 mg or placebo followed by treatment switch at week 12 and continuing until week 24. All participants from the double-blind study who enrolled into the OLE study received dazukibart 600 mg every 4 weeks for up to 48 weeks, with a total treatment period of 52 weeks (or 76 weeks of the combined double-blind and OLE study). Each participant was eligible to receive a total of 13 doses of dazukibart over the course of the OLE study (Figure 1A). Each dose of dazukibart was administered as a 60-minute IV infusion.
Assessment timepoints for the combined double-blind and OLE study were baseline or week 0 (double-blind); weeks 12 and 24 (double-blind); weeks 36, 48, 60, 72, and 76 (OLE); and weeks 84 and 92 (follow-up phase).
Outcomes. In the full analysis set, the treatment-emergent adverse events (TEAEs) were evaluated for all participants, from week 24 to week 92, as the key primary endpoint. Key secondary efficacy endpoints included (1) absolute values and change from baseline in CDASI-A score13,14 (weeks 0 through 92) at all scheduled timepoints, (2) Total Improvement Score15 (TIS; weeks 0 through 92) at all scheduled timepoints, and (3) change from baseline in the scores of 6 core set measures contributing to the TIS that included PGA,15,16 PtGA,15,16 MMT-8,14-16 Health Assessment Questionnaire–Disability Index (HAQ-DI),14-16 EmGA14-16 from the Muscle Disease Activity Assessment Tool (MDAAT),14 and creatine kinase (CK)14-16 data representing muscle enzymes (weeks 0 through 92 and at intermediate scheduled timepoints). During the OLE study, muscle-related endpoints (including EmGA, TIS, and MMT-8) were collected only for participants from the MP cohort, and PtGA was not collected for participants from the SP cohort.
The assessment of CDASI scores, MMT-8, and EmGA scores were highly recommended to be done by the same physician to reduce variability.
Statistical analysis. Safety was assessed in all participants included in the full analysis set. CDASI-A scores were assessed at designated timepoints in participants in the SP DM cohort, MP DM cohort, and pooled skin analysis set, whereas the TIS and 6 core set measure components were assessed in participants in the MP DM cohort; PGA was also assessed for participants in the SP DM cohort. Due to small sample size and treatment switches, the combined 92-week data were analyzed descriptively.
RESULTS
Participant disposition and baseline characteristics. Of the 30 participants eligible to enroll into the OLE study from the double-blind study, 9/14 (64%) participants in the SP DM cohort and 15/16 (94%) participants in the MP DM cohort were enrolled. Sixteen of these 24 participants comprised the pooled skin analysis set of the OLE; the remaining 8 participants were excluded because their baseline CDASI-A scores were < 14. Of the 24 participants who received dazukibart, 21 completed treatment and the study; however, all 24 participants were included in safety and efficacy analysis. Three discontinuations from the study treatment phase were reported either due to lack of efficacy, withdrawal by participant, or for another unspecified reason (Figure 1B). Of the 3 participants who discontinued, 2 participants did not proceed to the follow-up phase, whereas the third participant entered the follow-up phase but subsequently withdrew from the study (withdrawal by participant).
Baseline characteristics of participants in the SP and MP DM cohorts and pooled skin analysis set are presented in Table 1. The median age was 49.5 (range 21-68) years, 20/24 (83%) were female, and 23/24 (96%) were White. Nine of 24 participants (38%) had prior IVIG use, and 20/24 (83%) had prior use of systemic corticosteroids. The median baseline CDASI-A scores for the SP DM cohort, MP DM cohort, and pooled skin analysis set were 31.0 (range 19-37), 11.0 (range 1-33), and 25.5 (range 15-37), respectively (Table 1). Baseline characteristics of the participants and a summary of selected concomitant medications of participants across the 4 treatment sequences due to treatment switch are shown in Supplementary Tables S1-S2 (available with the online version of this article).
Key demographics and baseline clinical characteristics of participants.
Safety outcomes. Safety data for all participants (weeks 24-92) are shown in Table 2, and data for incidence and severity of overall TEAEs by system organ class/preferred term (weeks 24-92) for each cohort are presented in Supplementary Table S3 (available with the online version of this article). Three participants temporarily discontinued the study intervention due to a nontreatment-related nonserious AE (NSAE) of coronavirus disease 2019 (COVID-19), a nontreatment-related SAE of lower limb fracture, and a treatment-related NSAE of allergic dermatitis. No participants permanently discontinued due to an AE, and no deaths were reported.
Summary of TEAEs during week 24 to 92 (full analysis set).
The number (percentage) of participants reporting any TEAE was 7/9 (78%), 13/15 (87%), and 12/16 (75%) in the SP DM cohort, MP DM cohort, and pooled skin analysis set, respectively. TEAEs in the overall population were classified as mild (48/87, 55%), moderate (33/87, 38%), or severe (6/87, 7%). The number (percentage) of participants reporting mild, moderate, and severe TEAEs were 3/9 (33%), 7/15 (47%), and 6/16 (38%); 3/9 (33%), 5/15 (33%), and 4/16 (25%); and 1/9 (11%), 1/15 (7%), and 2/16 (13%) in the SP DM cohort, MP DM cohort, and pooled skin analysis set, respectively. COVID-19 was the most common TEAE (the study period included the COVID-19 pandemic, from December 20, 2021, to December 3, 2023), affecting 33%, 20%, and 25% of the participants in SP DM cohort, MP DM cohort, and pooled skin analysis set, respectively (Table 2). Two participants, one in each cohort, experienced moderate TEAEs of urticaria, which were not treatment-related. In the SP DM cohort, some of the other moderate TEAEs included sinusitis, upper respiratory infection, palpitations, and diarrhea. Severe TEAEs included a fall and compartment syndrome. In the MP DM cohort, some of the moderate TEAEs included influenza, chest discomfort, pneumonia, back pain, diabetic ketoacidosis, headache, and nephrolithiasis. The severe TEAEs included cholelithiasis, abdominal pain, and nausea (Supplementary Table S3, available with the online version of this article). Treatment-emergent SAEs were reported in 3 participants, representing 11% (n = 1) of the SP DM cohort and 13% (n = 2) of the MP DM cohort; there were 13% (n = 2) in the pooled skin analysis set. The 3 treatment-emergent SAEs of cholelithiasis, diabetic ketoacidosis, and lower limb fracture (due to a fall) were not treatment-related. One participant who reported nontreatment-emergent SAE of humerus fracture (due to a fall) in the double-blind study continued to and completed the OLE study.
Efficacy outcomes.
• CDASI-A score. A decrease in CDASI-A scores is indicative of an improvement in disease activity.7,13 In the SP DM cohort, CDASI-A scores reduced (ie, improved) from week 24 through week 76 (end of treatment phase) and week 92 (end of follow-up phase; Table 3). The median baseline CDASI-A score was 31.0 (range 19-37). At weeks 24, 76, and 92, the median posttreatment CDASI-A scores were 10.0 (range 3-13), 2.0 (range 0-15), and 2.0 (range 0-25), respectively. The median change from baseline CDASI-A scores improved at week 24 (−22.0 [range −28 to −9]), week 76 (−24.0 [range −33 to −12]), and week 92 (−22.0 [range −33 to −6]).
CDASI-A score (absolute and change from baseline) for all analysis sets.
In the MP DM cohort, the CDASI-A scores reduced (ie, improved) from week 24 through week 76, and increased (ie, worsened) from week 76 onward during the follow-up phase (although still lower than the baseline scores). The median baseline CDASI-A score was 11.0 (range 1-33). At weeks 24, 76, and 92, the median posttreatment CDASI-A scores were 4.0 (range 0-13), 1.0 (range 0-7), and 3.0 (range 0-22), respectively, and the median change from baseline CDASI-A scores were −8.0 (range −24 to 9), −9.0 (range −32 to 1), and −5.0 (range −32 to 1), respectively.
In the pooled skin analysis set, CDASI-A scores reduced (ie, improved) from week 24 through week 76 and increased from week 76 onward during the follow-up phase. The median baseline CDASI-A score was 25.5 (range 15-37). At weeks 24, 76, and 92, the median posttreatment CDASI-A scores were 8.5 (range 1-13), 2.0 (range 0-15), and 2.5 (range 0-25), respectively, and the median change from baseline CDASI-A scores were −20.0 (range −28.0 to −8.0), −23.5 (range −33 to −12), and −20.5 (range −33 to 1), respectively (Table 3).
Longitudinal CDASI-A scores are also presented by treatment sequence in each analysis set in Supplementary Figures S1-S3 (available with the online version of this article). For treatment sequences with > 1 participant, the CDASI-A scores decreased from week 24 through week 76, followed by an increase at week 92 after cessation of treatment (at week 76). The median change from baseline CDASI-Damage scores is presented in Supplementary Table S4.
• TIS. Since TIS is a relative measure of improvement, with a range of 0-100, absolute TIS is reported for postbaseline assessments (baseline TIS is 0 by definition).7 The mean TIS in the MP DM cohort from baseline (week 0 of double-blind study) through week 92 for the combined double-blind and OLE study is shown in Figure 2. During the treatment period, the median TIS values at weeks 24 and 76 were 62.5 (range 0.0-80.0) and 65.0 (range 2.5-95.0), respectively (Supplementary Table S5, available with the online version of this article), indicating major improvement with dazukibart treatment. At the end of follow-up phase (week 92), the median TIS was 55.0 (range 0.0-95.0). At week 76, 10/15 (67%) and 9/15 (60%) participants achieved at least a 40-point (ie, moderate) and 60-point (ie, major) improvement in TIS, respectively.16 At the end of the follow-up phase (week 92), 8/15 (53%) and 5/15 (33%) participants achieved moderate and major improvement in TIS, respectively (Supplementary Table S5).
Mean absolute values (90% CI) for Total Improvement Score in the MP DM cohort. Includes all participants with MP DM who were enrolled in stage III of the double-blind study and continued to OLE study. The first, second, and third treatments in the sequence described the treatment received and the outcomes assessed from baseline to week 12 (double-blind), week 12 to week 24 (double-blind), and week 24 to week 76 (OLE), respectively. DM: dermatomyositis; MP: muscle-predominant; OLE: open-label extension.
• Core set measures of the TIS. For the SP DM cohort, PGA values were reported during the OLE. At weeks 24, 76, and 92, the median change from baseline scores for PGA (in mm) were −50.0 (range −64.0 to 5.0), −56.0 (range −69.0 to −10.0), and −47.0 (range −69.0 to 3.0), respectively.
For the MP DM cohort at weeks 24, 76, and 92, the median change from baseline scores for MMT-8 were 17.0 (range −8 to 55), 28.5 (range 2 to 71), and 23.0 (range −10 to 61); PGA (in mm) were −30.0 (range −63.0 to 10.0), −38.0 (range −69.0 to −10.0), and −33.0 (range −70.0 to 10.0); PtGA (in mm) were −23.7 (range −80.0 to 38.0), −37.9 (range −74.0 to 1.0), and −20.9 (range −63.8 to 38.0); HAQ-DI were −0.1 (range −1.9 to 0.4), −0.4 (range −2.1 to 0.4), and −0.4 (range −1.3 to 1.0); EmGA (in cm) were −2.9 (range −5.4 to 1.8), −3.4 (range −5.6 to 1.7), and −1.1 (range −5.5 to 1.8); and CK (in U/L) were −21.0 (range −754 to 836), 2.5 (range −804 to 77), and 14.0 (range −684 to 92), respectively (Supplementary Table S5, available with the online version of this article; Figures 3A-F).
Mean change from baseline (90% CI) in the core set measures of Total Improvement Score in the MP DM cohort. Includes all participants with muscle-predominant DM who were enrolled in stage III of the double-blind study and continued to OLE study. The first, second, and third treatments in the sequence described the treatment received and the outcomes assessed from baseline to week 12 (double-blind), weeks 12 to 24 (double-blind), and weeks 24 to 76 (OLE), respectively. The follow-up phase included weeks 84 and 92. PGA was recorded from a standalone form. Both PGA and PtGA ranged from 0 (worst) to 100 (best) on a 100-mm VAS. During the OLE study, PtGA was collected from MP DM participants only. CK: creatine kinase; DM: dermatomyositis; EmGA: extramuscular global assessment; HAQ-DI: Health Assessment Questionnaire–Disability Index; MMT-8: manual muscle testing 8; MP: muscle-predominant; OLE: open-label extension; PGA: physician global assessment; PtGA: patient global assessment; VAS: visual analog scale.
DISCUSSION
In this analysis in adults with DM, the efficacy of dazukibart was assessed over a 24-week randomized phase II double-blind study,13 with eligible participants enrolling into a phase IIb OLE study (52 weeks). Here, we present combined long-term efficacy outcomes from the double-blind and OLE studies and safety outcomes from the OLE study. All participants entering the OLE study received at least 12 weeks of dazukibart treatment as part of the 24-week double-blind study (either before or after placebo). Improvement in key efficacy variables (change from baseline in CDASI-A score, TIS, and core set measures of TIS) and safety with dazukibart 600 mg were assessed during the OLE study.
Dazukibart was safe and well tolerated during the OLE (weeks 24 through 92), with most TEAEs classified as mild and no deaths or permanent discontinuations reported. Over an extended period of 68 weeks, the safety and tolerability results of this study were comparable with the safety data evaluated at 24 weeks after dazukibart treatment reported by Fiorentino et al13 (Supplementary Table S6, available with the online version of this article).
Treatment with dazukibart 600 mg or 150 mg led to a substantial improvement in CDASI-A scores from baseline through week 24 of the double-blind study.13 The improvement (decrease) in CDASI-A scores was sustained (dazukibart 600 mg) at week 76 across the 3 cohorts. Although the CDASI-A scores increased from weeks 76 to 92, they were still lower than the baseline scores, indicating a sustained improvement at week 92. The reduction in CDASI-A scores by ≥ 5 points at week 24 in nearly all patients in both the SP DM cohort and pooled skin analysis set indicated a clinically meaningful improvement, whereby a change of ≥ 5 points in CDASI-A scores is considered the minimum clinically significant change in patients with cutaneous disease.17 This reduction in CDASI-A scores was retained until week 76 in 9/9 (100%) and 14/16 (88%) of participants in the SP DM cohort and pooled skin analysis set, respectively. Further, at week 76, a reduction of ≥ 40% in CDASI-A scores from baseline, indicative of an improvement in patient-reported outcomes such as quality of life,13,18 was achieved by > 70% participants across analysis sets and was sustained through week 92. Overall, a clinically meaningful improvement in skin disease observed at week 1213 was sustained through week 92, even after 20 weeks posttreatment discontinuation.
An improvement (increase) in TIS at weeks 24, 76, and 92 was observed in the MP DM cohort with dazukibart 600 mg. This is a key measure of clinically meaningful improvement in muscle function in patients with MP DM.18 Major improvement was observed in 60% of participants at week 76 and was maintained by nearly 33% of participants at week 92, indicating a sustained improvement even after 20 weeks post treatment.
In the MP DM cohort, there was an overall improvement in the core set measures of TIS at weeks 24, 76, and 92 with dazukibart 600 mg. Increased MMT-8 scores—indicating a consistent improvement in muscle strength7—observed through week 76, were sustained beyond the treatment period with only a slight reduction from weeks 76 through 92. Reduction in both PGA and PtGA scores, indicating an improvement in disease activity,7 was observed following dazukibart treatment. PGA and PtGA scores reduced over the OLE treatment period (weeks 24 through 76), and this improvement was sustained over the 16-week follow-up phase. Despite a slight increase in the scores from weeks 76 onward, the effect was retained until week 92. HAQ-DI scores improved from baseline (ie, decreased from baseline through week 76 of the OLE) and were sustained during the follow-up phase.7 Similar improvement from baseline was also observed in EmGA scores at weeks 24, 76, and 92 with dazukibart 600 mg, indicating a decreased disease activity in extramuscular organs. A similar trend was observed with serum CK levels, a biomarker for muscle damage,19 in which there was an improvement (reduction) from baseline at week 76 of the OLE that remained within the normal range through week 92 of follow-up. This indicated a long-term improvement in the extent of muscle damage. Our results support the findings of other reports that discuss the significance of IFN-β pathway and efficacy of IFN-β inhibitors in DM treatment.20,21
The limitations of this study included variability in the efficacy scores and a small sample size in the muscle cohort, making it challenging to interpret treatment effect estimates in this population. This limitation underscores the need for a longer, adequately powered study in patients with muscle disease for a definite assessment of efficacy of dazukibart in DM. Notably, a global phase III randomized-controlled trial is currently underway (NCT05895786).
In conclusion, dazukibart was safe and well tolerated during the OLE from weeks 24 through 92. Treatment with dazukibart resulted in a rapid onset of efficacy, as observed by improvements in almost all efficacy measures assessed in both SP and MP cohorts in the double-blind study. The treatment response was sustained over an extended period of 52 weeks of the phase IIb OLE study in all cohorts, as evidenced by long-term improvement in efficacy outcomes and several patient-reported outcomes for skin- and muscle-specific endpoints. These results highlight the rapid response and sustained improvement with dazukibart treatment in participants with SP and MP DM, underscoring the potential of targeted IFN-β inhibition as an effective treatment strategy for both types of DM. Similar long-term studies are warranted in a larger patient population to further support the IFN-β inhibition strategy in DM.
ACKNOWLEDGMENT
This study was funded by Pfizer. The authors thank the International Myositis Assessment and Clinical Studies group for allowing the myositis assessment tools to be used in this trial. Medical writing support, under the direction of authors, was provided by Siddhi Gupta, PhD, ISMPP CMPP, Archana Patkar, PhD, ISMPP CMPP, and Reema Dhoke, PhD, and editorial support was provided by Kripa Madnani, PhD (all employees of Pfizer), and was funded by Pfizer, New York, USA.
Footnotes
CONTRIBUTIONS
RAV: conceptualization, investigation, supervision, and writing – review and editing. EP: conceptualization, funding acquisition, investigation, methodology, project administration, resources, supervision, and writing – review and editing. RA: conceptualization, methodology, supervision, and writing – review and editing. MC: conceptualization, methodology, project administration, supervision, and writing – original draft, review, and editing. AS: data curation, formal analysis, methodology, visualization, and writing – original draft, review and editing. NR: conceptualization, methodology, project administration, and writing – review and editing. EM: project administration, and writing – review and editing. DF: conceptualization, investigation, supervision, and writing – review and editing. All authors contributed to reviewing and editing the initial manuscript and approving the final version. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
FUNDING
This study was sponsored by Pfizer. Pfizer was involved in the study design, data collection, data analysis, data interpretation, writing, review, and approval of the manuscript.
COMPETING INTERESTS
RAV is a principal investigator (PI) for this trial and is a PI or consultant for Argenx, AbbVie, AstraZeneca, BMS, Eli Lilly, and Priovant. RA has received grants/research fundings from Mallinckrodt, Pfizer, BMS, Q32, EMD Serono, Janssen, and BI; and has served as a consultant for Octapharma, CSL Behring, BMS, EMD Serono, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, BI, Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, ActiGraph, Horizon, Teva, ANI, Nuvig, Capella, Cabaletta Bio, I-Cell, and Sanofi. EP, NR, AS, MC, and EM are employees of Pfizer and own Pfizer stocks. DF has served as a consultant to and received honoraria from Pfizer, BMS, Biogen, Priovant, Argenx, IgM, J&J, Merck, and Kyverna; and has received research fundings from Argenx, Priovant, and EMD Serono.
ETHICS AND PATIENT CONSENT
The trial was conducted at 15 sites, including 1 site in Hungary, 2 sites in Poland, 1 site in Spain, and 11 sites in the US. The study was registered with ClinicalTrials.gov (NCT05192200). The study was approved by the institutional review board or ethics committee of each site (Hungary: IV/10588-0/2021-EKL; Poland: 31/2021, 31/2021; Spain: 22/092; and the US: i21-01421, 202111087, 850352, 22/279, 22-002634, 22-00264, SSU00176459 [Advarra], SSU00182900 [Advarra], SSU00185342 [Advarra], SSU00176566 [Advarra], and SSU00176876 [Advarra]). The combined double-blind and OLE study was conducted in accordance with the protocol and consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences 2002 International Ethical Guidelines, applicable International Council for Harmonization Guideline for Good Clinical Practice Guidelines, and other applicable laws and regulations, including privacy laws. All patients or their legally authorized representatives provided written informed consent before enrolling in the study.
DECLARATION OF AI USE
Pfizer’s generative artificial intelligence tool MAIA 3.0 (Medical Artificial Intelligence Assistant; GPT-4 based LLM) was used to assist production of sections of the first draft of the manuscript. AI output was refined and verified by the writing team and author group prior to inclusion in the draft.
DATA AVAILABILITY
Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/data-and-results for more information.
- Accepted for publication July 15, 2026.
- Copyright © 2026 by the Journal of Rheumatology
This is an Open Access article, which permits use, distribution, and reproduction, without modification, provided the original article is correctly cited and is not used for commercial purposes.
REFERENCES
SUPPLEMENTARY DATA
Supplementary material accompanies the online version of this article.
