Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis

Abstract

The dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD). OBJECTIVE To assess the efficacy and safety of different dupilumab regimens in maintaining response after 16 weeks of initial treatment. DESIGN, SETTING, AND PARTICIPANTS The Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (LIBERTY AD SOLO-CONTINUE) was a randomized, double-blind, phase 3 clinical trial conducted from March 25, 2015, to October 18, 2016, at 185 sites in North America, Europe, Asia, and Japan. Patients with moderate to severe AD who received dupilumab treatment and achieved an Investigator's Global Assessment score of 0 or 1 or 75% improvement in Eczema Area and Severity Index scores (EASI-75) at week 16 in 2 previous dupilumab monotherapy trials (LIBERTY AD SOLO 1 and 2) were rerandomized in SOLO-CONTINUE. After completing SOLO-CONTINUE, patients were followed up for up to 12 weeks or enrolled in an open-label extension. Data were analyzed from December 5 to 12, 2016. INTERVENTIONS High-responding patients treated with dupilumab in SOLO were rerandomized 2:1:1:1 to continue their original regimen of dupilumab, 300 mg, weekly or every 2 weeks or to receive dupilumab, 300 mg, every 4 or 8 weeks or placebo for 36 weeks. MAIN OUTCOMES AND MEASURES Percentage change in EASI score from baseline during the SOLO-CONTINUE trial, percentage of patients with EASI-75 at week 36, and safety. RESULTS Among the 422 patients (mean [SD] age, 38.2 [14.5] years; 227 [53.8%] male), continuing dupilumab treatment once weekly or every 2 weeks maintained optimal efficacy, with negligible change in percent EASI improvement from SOLO 1 and 2 baseline during the SOLO-CONTINUE trial (−0.06%; P < .001 vs placebo); percent change with the other regimens dose-dependently worsened (dupilumab every 4 weeks, −3.84%; dupilumab every 8 weeks, −6.84%; placebo, −21.67%). More patients taking dupilumab weekly or every 2 weeks (116 of 162 [71.6%]; P < .001 vs placebo) maintained EASI-75 response than those taking dupilumab every 4 weeks (49 of 84 [58.3%]) or every 8 weeks (45 of 82 [54.9%]) or those taking placebo (24 of 79 [30.4%]). Overall adverse event incidences were 70.7% in the weekly or every 2 weeks group, 73.6% in the every 4 weeks group, 75.0% in the every 8 weeks group, and 81.7% in the placebo group. Treatment groups had similar conjunctivitis rates. Treatment-emergent antidrug antibody incidence was lower with more frequent dupilumab dose regimens (11.3% in the placebo group and 11.7%, 6.0%, 4.3%, and 1.2% in the dupilumab every 8 weeks, every 4 weeks, every 2 weeks, and weekly groups, respectively). CONCLUSIONS AND RELEVANCE In this trial, continued response over time was most consistently maintained with dupilumab administered weekly or every 2 weeks. Longer dosage intervals and placebo resulted in a diminution of response for both continuous and categorical end points. No new safety signals were observed. The approved regimen of 300 mg of d...

Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: a systematic review for the EAACI Biologicals Guidelines

“…Nine additional articles were suggested by the GDG group but excluded due to dose not approved by the regulatory authorities, non-randomised double-blind study design, not reporting outcomes of interests, or duplicate data (Table S3). The SR for the efficacy and safety included seven RCTs (36,37,38,39,40,41) ( figure 1A). For the economic evidence, after screening 1552 hits, five studies were considered suitable for inclusion (51,52, 53, 54,55) (figure 1B).…”

“…The pooled analysis showed that dupilumab reduces symptoms of anxiety and depression with high certainty of evidence in adults (MD -3.08; 95%CI -4.41 to -1.75) and with moderate certainty in adolescents (MD -1.30; 95%CI -3.38 to +0.78). In the 36 weeks follow-up of SOLO trials an opposite effect was reported (MD 0.31, 95%CI 0.04 to 0.57) (41). Two RCTs (38,39)) evaluated this outcome as the proportion of the patients with no clinically relevant symptoms of anxiety and depression at 16 weeks (RR 1.78; 95% CI 1.35 to 2.33) and one of the two RCTs reported a better effect at 52 weeks (RR 2.40; 95%CI 1.5 to 3.87) (38).…”

“…Their results showed a significant increase in EASI- 50 (41). The effect on pruritus was also quantified by percent change from baseline of peak pruritus NRS score (36,37,38,39,40,41). The pooled analysis illustrated a significant dupilumab-induced NRS score improvement at 16 weeks for adults (MD -28.04%; 95% CI -32.65% to -23.43%) and for adolescents (MD -28.90%; 95% CI -39.34% to -18.46%).…”

“…All six RCTs also reported the proportion of patients with 50% improvement (EASI-50) at 16 weeks. Their results showed a significant increase in EASI- 50 (41). The effect on pruritus was also quantified by percent change from baseline of peak pruritus NRS score (36,37,38,39,40,41).…”

“…Follow-up under treatment ranged from 16 weeks (36,37,39,40) to one year (38). One RCT recruited responders from SOLO trials and continued the intervention for another 36 weeks (41). In all trials evaluated only regulatory-approved doses were considered.…”