Introduction
Guselkumab and risankizumab are monoclonal antibody treatments targeting interleukin 23 that are approved for the treatment of moderate to severely active ulcerative colitis (UC) in the United States. However, these agents have not been directly compared in a controlled setting.
Aims & Methods
A network meta-analysis (NMA) was conducted to compare guselkumab and risankizumab as maintenance therapy for UC, based on key outcomes from pivotal Phase 3 randomised controlled trials (RCTs). The COMMAND trial of risankizumab and the QUASAR trial of guselkumab were identified through systematic literature review. Frequentist, fixed-effect NMAs were conducted for key efficacy endpoints at the end of maintenance (52 weeks in COMMAND and 44 weeks in QUASAR) as reported by the trials: clinical remission, endoscopic improvement, endoscopic remission, and histologic endoscopic mucosal improvement (HEMI). Analyses included populations of variable advanced therapy (ADT) failure status (i.e., mixed). Data from these re-randomized RCTs were used directly, rather than normalising to mimic treat-through designs, given these trials are for same-class therapies and were similarly designed.
Results
NMAs found that guselkumab 200 mg every 4 weeks (Q4W) was significantly more efficacious than risankizumab 360 mg every 8 weeks (Q8W) on clinical remission (odds ratio [OR] 2.38; 95% confidence interval [CI] 1.25, 4.52) and endoscopic improvement (OR 2.26; 95% CI 1.21, 4.22). Guselkumab 200 mg Q4W had numerical benefits on endoscopic remission (OR 1.53; 95% CI 0.74, 3.16) and HEMI (OR 1.89; 95% CI 0.98, 3.63) compared with risankizumab 360 mg Q8W. Numerically higher benefits of guselkumab compared with risankizumab were also observed at lower doses (ie, guselkumab 100 mg Q8W and risankizumab 180 mg Q8W).
Conclusion
Results of this NMA suggest that guselkumab 200 mg Q4W is superior to risankizumab 360 mg Q8W for maintenance treatment of moderate to severely active UC on multiple efficacy endpoints including endoscopic improvement.
Table. Results summary for NMAs comparing guselkumab and risankizumab on clinical and endoscopic outcomes in UC.*
| Clinical remission
| Endoscopic improvement
| Endoscopic remission
| HEMI
|
GUS 100 mg Q8W
| GUS 200 mg Q4W
| GUS 100 mg Q8W
| GUS 200 mg Q4W
| GUS 100 mg Q8W
| GUS 200 mg Q4W
| GUS 100 mg Q8W
| GUS 200 mg Q4W
|
RIS 180 mg Q8W
| 1.76 (0.92, 3.35)
| 2.13 (1.12, 4.06)†
| 1.88 (1.00, 3.53)
| 2.04 (1.09, 3.83)†
| 1.71 (0.82, 3.55)
| 1.64 (0.79, 3.41)
| 1.55 (0.81, 3.00)
| 1.85 (0.96, 3.56)
|
RIS 360 mg Q8W
| 1.96 (1.03, 3.74)†
| 2.38 (1.25, 4.52)†
| 2.07 (1.11, 3.88)†
| 2.26 (1.21, 4.22)†
| 1.59 (0.77, 3.29)
| 1.53 (0.74, 3.16)
| 1.59 (0.83, 3.06)
| 1.89 (0.98, 3.63)
|
PBO
| 3.53 (2.22, 5.61)†
| 4.28 (2.70, 6.78)†
| 4.19 (2.64, 6.65)†
| 4.56 (2.87, 7.23)†
| 2.93 (1.79, 4.82)†
| 2.82 (1.72, 4.63)†
| 3.82 (2.37, 6.15)†
| 4.54 (2.82, 7.30)†
|
GUS = guselkumab, HEMI = histologic endoscopic mucosal improvement, NMAs = network meta-analyses, PBO = placebo, Q4W = every four weeks, Q8W = every 8 weeks, RIS = risankizumab, UC = ulcerative colitis. *Data are presented as odds ratio (95% confidence interval). †Significantly favours GUS (ie, confidence interval does not include 1). Note: clinical remission is defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic remission is defined as an endoscopic subscore of 0, and HEMI is defined as a combination of histologic and endoscopic improvement
|
Disclosure
Elise Wu, Dominik Naessens, and Mario Gomez are employees of and may hold stock/stock options in Johnson & Johnson. Ashley Bonner and Maxwell Jones are employees of EVERSANA.