Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study

Abstract

Background and aims: Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn's disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study.

Methods: Enrolled patients had achieved clinical response [decrease in Crohn's Disease Activity Index from baseline ≥100] without clinical remission [Crohn's Disease Activity Index <150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks.

Results: Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The rate of serious adverse events was 24.6 events/100 patient-years; the majority were gastrointestinal in nature. Rates of serious infections, opportunistic infections and fungal infections were 4.2, 1.8, and 6.6 events/100 patient-years, respectively. No deaths, malignancies, adjudicated major adverse cardiovascular events, latent/active tuberculosis or herpes zoster were reported. Treatment-emergent anti-drug antibodies developed in eight patients [12.3%]; none were neutralizing. Efficacy outcomes were maintained during the study, including the proportions of patients [observed analysis] with clinical remission [>71%] and endoscopic remission [>42%].

Conclusions: Long-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn's disease, with no new safety signals. Clinical trial registration number: NCT02513459.

Keywords: Crohn’s disease; long-term safety; open-label extension.

© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.

Figures

Figure 1.

Study design and patient disposition. aPrimary reasons for discontinuation. bOther reasons are as reported by the investigator [as free text] and have not been grouped to avoid inaccuracy in reporting. cPatients rolled over to the ongoing phase 3 OLE [M16-000 sub-study 3] between Weeks 128 and 184 of M15-989. AE, adverse event; CD, Crohn’s disease; IV, intravenous; OLE, open-label extension; Q4/8W, every 4/8 weeks; SC, subcutaneous.

Figure 2.

Risankizumab trough plasma concentration over time in all patients. Analysis set included all patients with available pharmacokinetics and ADA data. Patients rolled over to the ongoing phase 3 OLE [M16-000 sub-study 3] between Weeks 128 and 184, and as a result had different last visit time points. ADA, anti-drug antibody; OLE, open-label extension; SC, subcutaneous; SD, standard deviation.

Figure 3.

Proportions of patients achieving clinical remission [A], CDEIS remission [B], IBDQ response [C] and IBDQ remission [D] over time [intent-to-treat analysis set]. From Week 128 onwards, patients could roll over to the ongoing phase 3 OLE [M16-000 sub-study 3]. This resulted in a decrease in the number of patients continuing towards completion in the current phase 2 OLE study and prior to rollover into the phase 3 OLE for further risankizumab treatment and follow-up. Therefore, NRI for missing data was not presented after Week 128. Only observed cases were presented beyond Week 128. n denotes the number of responders and N denotes the number of patients at risk. CDAI, Crohn’s Disease Activity Index; CDEIS, Crohn’s Disease Endoscopic Index of Severity; IBDQ, Inflammatory Bowel Disease Questionnaire; NRI, non-responder imputation; OLE, open-label extension.

Figure 3.

Proportions of patients achieving clinical remission [A], CDEIS remission [B], IBDQ response [C] and IBDQ remission [D] over time [intent-to-treat analysis set]. From Week 128 onwards, patients could roll over to the ongoing phase 3 OLE [M16-000 sub-study 3]. This resulted in a decrease in the number of patients continuing towards completion in the current phase 2 OLE study and prior to rollover into the phase 3 OLE for further risankizumab treatment and follow-up. Therefore, NRI for missing data was not presented after Week 128. Only observed cases were presented beyond Week 128. n denotes the number of responders and N denotes the number of patients at risk. CDAI, Crohn’s Disease Activity Index; CDEIS, Crohn’s Disease Endoscopic Index of Severity; IBDQ, Inflammatory Bowel Disease Questionnaire; NRI, non-responder imputation; OLE, open-label extension.