Jeanne Jiang, PhD1, Sun Choi, MS, PhD1, Ben Muller, 1, Cynthia Tsang, 1, Abigail Wojtowicz, 1, Aurelia Little, 2, Cheryl Ferrufino, 2, Pinar Bilir, 3, Pallavi Krishnamurthy, 3, Tao Fan, MS, PhD1 1Takeda Pharmaceuticals U.S.A., Inc., Lexington, MA; 2IQVIA, Falls Church, VA; 3IQVIA, San Francisco, CA
Introduction: The treatment landscape for moderate to severe ulcerative colitis (UC) in the USA is evolving rapidly. There is an increasing number of advanced therapies for healthcare providers, payers, and patients to consider. The number needed to treat (NNT) is an index of clinical efficacy that is often used to inform treatment choice and formulary decision making in the absence of direct head-to-head randomized controlled trials (RCTs).
Methods: For this analysis, clinical remission data were extracted from 11 published RCTs investigating advanced therapies (biologics or small molecules) versus placebo for the maintenance of clinical remission in adults with moderate to severe UC. Clinical remission was defined in the RCTs as a modified Mayo score ≤ 2 (with no sub-score > 1) at 52–54 weeks of treatment, with some exceptions. NNTs and 95% confidence intervals (95% CIs) were calculated using the Wilson score method1 for the overall patient population and, if data were available, for subgroups of patients who were biologic-naïve or biologic-experienced.
Results: Figure 1 shows the NNTs to maintain clinical remission for each of the advanced therapies in patients with moderate to severe UC. For the overall population, upadacitinib 30 mg taken orally (PO) once daily (OD) had the lowest NNT (2.51; 95% CI 2.05, 3.34); adalimumab 40 mg administered subcutaneously (SC) once every 2 weeks (Q2W) had the highest NNT (11.36; 95% CI 6.78, 34.63). When stratified by previous biologic use, vedolizumab 108 mg SC Q2W had the lowest NNT (2.87; 95% CI 2.02, 6.45) for maintaining remission in biologic-naïve patients and upadacitinib had the lowest NNT (2.38; 95% CI 1.86, 3.51) in biologic-experienced patients. Adalimumab had the highest NNT both in biologic-naïve (10.43; 95% CI 5.52, 108.09) and biologic-experienced (13.82; 95% CI 6.64, 622.24) patients.
Discussion: Vedolizumab, an anti-α4β7 integrin blocker, had the lowest NNT among first-line advanced therapies for maintaining clinical remission in patients with moderate to severe UC. Upadacitinib, a Janus kinase inhibitor that is currently indicated as a second-line advanced therapy, had the lowest NNT in biologic-experienced patients. Alongside safety and cost considerations, the NNTs may inform drug choice and formulary decision making for the maintenance of clinical remission in moderate to severe UC.
Reference
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Figure: Figure 1. NNT to maintain clinical remission in patients with moderate to severe UC overall and stratified by previous biologic treatment (naïve or experienced). Error bars denote 95% CI. BID, twice daily; CI, confidence interval; ES, endoscopic; FDA, Food and Drug Administration; IV, intravenously; NNT, number needed to treat; OD, once daily; PO, taken orally; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; Q12W, every 12 weeks; RB, rectal bleeding; SC, subcutaneously; SF, stool frequency; UC, ulcerative colitis.
a For etrasimod, clinical remission was defined using the modified Mayo Score as SF sub-score = 0 (or = 1 with a ≥ 1-point decrease from baseline), RB sub-score =0, and ES sub-score ≤ 1 (excluding friability), and without corticosteroid exposure during at least 12 weeks before Week 52. b As of May 2023, etrasimod and mirikizumab are not approved by the FDA for treating UC. c Patients in clinical remission at week 6 for golimumab and vedolizumab, week 8 for tofacitinib, upadacitinib and ustekinumab, and week 10 for ozanimod were re-randomized for the maintenance phase, which may enrich the trial population and affect NNT. d For mirikizumab, clinical remission was assessed at week 40 with the modified Mayo Score and defined as achieving sub-scores of SF = 0 or SF = 1 with ≥ 1-point decrease from baseline, RB = 0, and ES = 0 or 1 (excluding friability). e As of May 2023, tofacitinib is only indicated for the treatment of adult patients with moderately to severely active UC who have had an inadequate response or intolerance to ≥ 1 tumor necrosis factor blockers. Additionally, tofacitinib 10 mg BID is indicated for long-term use only in limited situations. f As of May 2023, upadacitinib is indicated for the treatment of adult patients with moderately to severely active UC only when they have had an inadequate response or intolerance to ≥ 1 tumor necrosis factor blockers. g For upadacitinib, clinical remission was defined as SF sub-score ≤ 1 and not greater than baseline, RB sub-score = 0, and ES sub-score ≤ 1 without friability. h The negative upper CI indicates that there may be a scenario in which treatment may lead to an adverse effect, hence the NNT should be interpreted with caution.
Sun Choi: Takeda Pharmaceuticals U.S.A., Inc. – Employee, Stock Options.
Ben Muller: Takeda Pharmaceuticals U.S.A., Inc. – Employee, Stock Options.
Cynthia Tsang: Takeda Pharmaceuticals U.S.A., Inc. – Employee, Stock Options.
Abigail Wojtowicz: Takeda Pharmaceuticals U.S.A., Inc. – Employee, Stock Options.
Aurelia Little: IQVIA – Employee. Takeda Pharmaceuticals U.S.A., Inc. – contracted by Takeda to conduct the study.
Cheryl Ferrufino: IQVIA – Employee. Takeda Pharmaceuticals U.S.A., Inc. – contracted by Takeda to conduct the study.
Pinar Bilir: IQVIA – Employee. Takeda Pharmaceuticals U.S.A., Inc. – contracted by Takeda to conduct the study.
Pallavi Krishnamurthy: IQVIA – Employee. Takeda Pharmaceuticals U.S.A., Inc. – contracted by Takeda to conduct the study.
Tao Fan: Takeda Pharmaceuticals U.S.A., Inc – Employee, Stock Options.
Jeanne Jiang, PhD1, Sun Choi, MS, PhD1, Ben Muller, 1, Cynthia Tsang, 1, Abigail Wojtowicz, 1, Aurelia Little, 2, Cheryl Ferrufino, 2, Pinar Bilir, 3, Pallavi Krishnamurthy, 3, Tao Fan, MS, PhD1. P3646 - Number Needed to Treat to Maintain Clinical Remission With Advanced Therapies in Patients with Moderate to Severe Ulcerative Colitis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.
