Table 3.

Effect of luspatercept exposure or clearance on the probability of achieving erythroid response after adjusting for significant baseline covariates

Study	Patients	Efficacy end point	Covariate adjusted a	PK measure b	OR (95% CI)	P value
Phase II + III	No dose escalation	RBC‐TI ≥ 8 weeks in weeks 1–15	RBCT, EPO	AUCavg	1.936 (1.27, 3.105)	0.0017
Phase II + III	No dose escalation	RBC‐TI ≥ 8 weeks in weeks 1–15	RBCT, EPO, AUCavg	CL/F	0.699 (0.547, 0.863)	0.0003
Phase II + III	All	RBC‐TI ≥ 8 weeks in weeks 1–15	RBCT, EPO, BIL	AUCavg	1.348 (1.017, 1.809)	0.0382
Phase II + III	All	RBC‐TI ≥ 8 weeks in weeks 1–15	RBCT, EPO, BIL, AUCavg	CL/F	0.712 (0.558, 0.874)	0.0003
Phase III only	All	RBC‐TI ≥ 8 weeks in weeks 1–15	RBCT, BIL	AUCavg	1.167 (0.810, 1.695)	0.4058
Phase III only	All	RBC‐TI ≥ 8 weeks in weeks 1–15	RBCT, BIL	CL/F	0.755 (0.605, 0.891)	0.0001
Phase III only	All	RBC‐TI ≥ 8 weeks in weeks 1–24	RBCT, EPO, age	AUCavg	0.993 (0.731, 1.346)	0.9628
Phase III only	All	RBC‐TI ≥ 8 weeks in weeks 1–24	RBCT, EPO, age	CL/F	0.833 (0.695, 0.961)	0.0082
Phase III only	All	RBC‐TI ≥ 12 weeks in weeks 1–24	RBCT, age, BIL	AUCavg	1.103 (0.797, 1.527)	0.5505
Phase III only	All	RBC‐TI ≥ 12 weeks in weeks 1–24	RBCT, age, BIL	CL/F	0.620 (0.463, 0.790)	< 0.0001
Phase III only	All	IWG mHI‐E in weeks 1–24	BIL	AUCavg	1.101 (0.857, 1.422)	0.4505
Phase III only	All	IWG mHI‐E in weeks 1–24	BIL	CL/F	0.818 (0.710, 0.919)	0.0003

AUC_avg, average area under the concentration–time curve during the evaluation period; BIL, baseline total bilirubin; CI, confidence interval; CL/F, apparent clearance; EPO, baseline serum erythropoietin; IWG, International Working Group; mHI‐E, modified hematologic improvement–erythroid; OR, odds ratio for PK measure; PK, pharmacokinetics; RBCT, red blood cell transfusion burden; RBC‐TI, red blood cell transfusion independence.

^aOnly statistically significant covariates are included, tested by the likelihood ratio test in the same order as shown.

^bAs the last covariate added in the likelihood ratio test.