OBJECTIVES: Estimate comparative efficacy for opioid induced constipation (OIC) among adults with chronic non-cancer pain for: 1) naldemedine monotherapy (NLD) versus rescue laxatives (LAX); 2) naldemedine plus stable laxative (NLD+) versus stable laxative plus LAX (LAX+); and 3) naldemedine monotherapy versus naloxegol 25mg monotherapy (NLX) in patients with prior laxative inadequate response (LIR).

METHODS: For 1) NLD vs LAX, we analysed a subset of the pooled intention-to-treat (ITT) population of the Phase III randomized control trials (RCTs), COMPOSE-1 and -2 (C1&2). NLD patients not requiring rescue laxative during the 12-week double-blind observation period and LAX patients taking placebo and rescue laxative were selected. For 2) NLD+ vs LAX+, we analysed the ITT subset of the COMPOSE-3 RCT continuing stable laxatives throughout who either took NLD or placebo plus rescue laxative. Finally, for we conducted an indirect treatment comparison of the pooled ITT LIR subsets of C1&2 and KODIAC-04 & -05 respectively. The outcomes were non-OIC status (>3 per week of bowel movements (BMs)): for 1) spontaneous BMs (SBMs) for NLD and BMs for LAX at Week 4 and Week 12.; for 2) BMs at Week 12; and for 3) SBMs at Week 4.

RESULTS: For 1) the odds ratios (OR) of NLD achieving non-OIC status over LAX were 3.95 (95% CI 2.06 to 7.57) and 4.40 (2.46-7.84) at Weeks 4 and 12 respectively (p<0.0001). For 2) the outcome OR for NLD+ vs LAX+ at week 12 was 1.68 (1.23-2.31; p=0.0012). For 3) the outcome OR for NLD vs NLX at week 12 was 4.07 (1.19-13.9; p=0.0249).

CONCLUSIONS: In patients with OIC and chronic non-cancer pain, naldemedine proved superior to not only rescue laxatives when used either as monotherapy or in combination with an established laxative regimen but also to naloxegol 25mg monotherapy in LIR patients.