P011 A number needed to harm analysis of safety outcomes from randomized controlled trials of biologics and tofacitinib in ulcerative colitis
Authors: KT Park , Trevor Lissoos , Greg Hather , Aimee Blake , Haridarshan Patel 
Published: July 2019

BACKGROUND:
Emerging evidence on vedolizumab supports its safety profile given its unique gut-specific mechanism of action. Long-term safety is an important outcome when choosing between treatment options for moderately to severely active ulcerative colitis (UC). A systematic literature review and indirect treatment comparison examined published evidence on safety outcomes reported from randomized controlled trials (RCTs) of approved biologics and tofacitinib in UC.

METHODS:
MEDLINE, Embase, and Cochrane Library databases were searched from 1997 to July 2018 to identify RCTs reporting safety outcomes with biologic agents (vedolizumab, adalimumab, infliximab, golimumab, ustekinumab, certolizumab, natalizumab) and tofacitinib approved to treat moderately to severely active UC. All maintenance treatment studies (follow-up, 44–60 weeks) were included. A network meta-analysis estimated odds ratios (ORs) using vedolizumab as reference treatment for the following safety measures assessed at approximately 52 weeks: overall adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, overall infections, serious infections, and arthralgia. Number needed to harm (NNH), defined as the additional number of patients that would have to be treated with vedolizumab for one person to experience a safety outcome, was also calculated. A positive NNH denotes better safety with vedolizumab compared with other agents, with higher NNH values representing a correspondingly better safety profile for vedolizumab vs the given comparator treatment option.

RESULTS:
Of 3,102 publications identified, 6 RCTs (2 golimumab; 1 each vedolizumab, adalimumab, infliximab, and tofacitinib) were eligible for inclusion. Compared with vedolizumab, all ORs for SAEs trended higher for other treatment options (adalimumab: 1.99 [95% credible interval (CI) 0.84–4.70]; infliximab: 1.73 [0.76–3.97]; and tofacitinib: 1.66 [0.62–4.39]) or achieved statistical significance (golimumab: 2.55 [1.10–5.70]). The NNH values for SAEs were adalimumab: 18; infliximab: 24; golimumab: 12; and tofacitinib: 27. For AEs leading to discontinuation, ORs trended higher for other treatment options relative to vedolizumab (adalimumab: 2.32 [0.48–12.68]; infliximab: 3.48 [0.68–21.70]; golimumab: 3.43 [0.74–20.90]; tofacitinib: 1.61 [0.34–8.95]). The NNH values for AEs leading to discontinuation were adalimumab: 29; infliximab: 16; golimumab: 16; and tofacitinib: 63. For serious infections, ORs again trended higher for other treatment options (adalimumab: 1.23 [0.16–8.76]; infliximab: 1.78 [0.29–10.67]; golimumab: 4.09 [0.66–25.99]; tofacitinib: 1.28 [0.12–16.05]). The NNH values for serious infections were adalimumab: 333; infliximab: 100; golimumab: 25; and tofacitinib: 250. Similar numerical trends were observed with vedolizumab for the safety outcomes of overall AEs, overall infections, and arthralgia.

CONCLUSION(S):
In a network meta-analysis of RCTs, vedolizumab consistently demonstrated better safety profile trends relative to other approved treatment options for moderately to severely active UC. Vedolizumab had the highest NNH values for all safety outcomes, especially serious infections. These indirect comparison results were limited to RCT patient populations, and real-world studies in larger patient populations are needed to confirm these findings.