Efficacy and safety of guselkumab, administered with a novel patient-controlled injector (One-Press), for moderate-to-severe psoriasis: results from the phase 3 ORION study

Abstract

Objectives: Guselkumab, an interleukin-23 antagonist, is approved for self-administration with the UltraSafe Plus TM syringe to treat moderate-to-severe plaque-type psoriasis. We evaluated the efficacy, safety, pharmacokinetics, and acceptability of guselkumab administered using a novel patient-controlled injector (One-Press) in psoriasis patients. Materials and methods: This Phase 3, multicentre, double-blind, placebo-controlled study (ORION, Clinicaltrials.gov identifier-NCT02905331) randomized adults with moderate-to-severe psoriasis (4:1) to guselkumab 100 mg at Weeks 0/4/12/20/28 or placebo at Weeks 0/4/12 with crossover to guselkumab 100 mg at Weeks 16/20/28. Week 16 co-primary endpoints were the proportions of patients achieving Investigator Global Assessment (IGA) cleared/minimal (IGA 0/1) and Psoriasis Area and Severity Index 90% improvement (PASI90) responses. One-Press usability/acceptability was evaluated using the Self-Injection Assessment Questionnaire (SIAQ) and Patient-Controlled Injection Device Questionnaire. Final assessments occurred at Week 40. Results: At Week 16, significantly higher proportions of guselkumab-treated (N ¼ 62) than placebo-treated (N ¼ 16) patients achieved IGA 0/1 (80.6% vs. 0.0%, p < .001) and PASI90 (75.8% vs. 0.0%, p < .001) responses. Adverse events were comparable between treatments. SIAQ results demonstrated 99% (68/69) of patients were satisfied/very satisfied with One-Press at Week 28. Conclusions: Guselkumab administered using the One-Press patient-controlled injector was efficacious and well-tolerated in moderate-to-severe psoriasis patients, consistent with previously reported Phase-3 studies of guselkumab administered using UltraSafe Plus. One-Press was highly acceptable to patients.

Assessing the relative efficacy of interleukin-17 and interleukin-23 targeted treatments for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis of PASI response

“…Thirty studies [32, 61, 62, 71, 73, 79, 84, 85, 92–95, 97, 102–105, 108, 109, 114–118, 121, 123, 126–128, 131], were excluded from the network in the sensitivity analysis which restricted trial inclusion to those that reported a minimum of 5% of patients with prior biologic exposure. Among these studies were all five studies [102–105, 109] evaluating the lower dose of etanercept (50 mg weekly) and the only study evaluating DMF [131].…”

“…A sensitivity analysis was carried out to test the effect of using 12-week rather than 16-week outcomes from three secukinumab trials (CLEAR [78], SIGNATURE [81] and CLARITY [82]). To test for small study bias, a further sensitivity analysis was carried out excluding the eighteen trials with fewer than 50 patients per trial arm [73, 84, 85, 100, 134–147]. There were no major differences between the results of these sensitivity analyses and the base-case analysis.…”

“…This NMA is the first to include risankizumab, and the recently licensed certolizumab pegol in its licensed dose. As our searches have been carried out recently, we have also included a number of recent trials that were not previously included in any NMA [72, 73, 79, 81–84].…”

The TNF/IL‐23/IL‐17 axis—Head‐to‐head trials comparing different biologics in psoriasis treatment

“…This may be preferred by individuals who experience injection‐site erythema, which is a common adverse event during etanercept treatment 107 . Moreover, auto‐injectors for guselkumab can help to improve patient adherence to self‐administration of subcutaneous injections with this potential stressful task 111 . Thus, studies show that IL‐23p19 inhibitors are a good therapeutic option in treating chronic plaque psoriasis, but the real test will be how these biologics perform in the real‐world clinical application.…”

Classification and mitigation of negative injection experiences with biologic medications

“…Various factors contribute to NIEs. The chemical and physical properties of biologics that may contribute to NIEs are summarized in Table 3 (Abbvie, 2018;Eshtiaghi & Gooderham, 2018;European Medicines Agency, 2005Ferris et al, 2019;Immunex Corporation, 2016;Kavanaugh et al, 2012;Lacour et al, 2017;Nakamura et al, 2017;Papp et al, 2016;Sator, 2018;Savage, Wittmann, Mcgonagle, & Helliwell, 2015;US Food and Drug Administration, 2008, 2011, 2017a, 2017c, 2017d, 2018a, 2018b, 2018c, 2019a, 2019bvan der Heijde et al, 2018).…”