Table 2.

Summary of the results of adverse events by category of the meta-analyses

AE-related categories	No. of studies	Experimental		Control		Risk ratio M–H to random (95% CI)	Heterogeneity (%)	Overall effect	Subgroup comparisona	Study causing homogeneity
		Events	Total	Events	Total
CGRP(R) mAbs						Primary analysis
Cognitive	8	68	3356	35	2215	1.12 (0.61–2.04)	39	p = 0.72	p = 0.03*
Sensory & pain	6	68	1893	43	1058	0.99 (0.37–2.66)	79*	p = 0.99	p < 0.001*
Gastrointestinal	7	79	3237	57	2091	0.83 (0.40–1.73)	60*	p = 0.63	p = 0.10
Infection & infestation	8	589	3356	348	2215	1.05 (0.93–1.19)	0	p = 0.43	p = 0.46
Administration site condition	7	716	2690	325	1993	1.58 (1.20–2.07)	69*	p = 0.001*
General & other	6	87	1857	50	1314	1.14 (0.58–2.26)	64*	p = 0.70	p = 0.13

CGRP(R) mAbs						Sensitivity analysis
Cognitive	8	68	3356	35	2215	1.12 (0.61–2.04)	39	p = 0.72	p = 0.03*
Sensory and pain	5	45	2930	43	1783	0.65 (0.34–1.24)	55	p = 0.19	p < 0.001*	EVOLVE-1
Gastrointestinal	6	61	2723	57	1896	0.83 (0.40–1.73)	46	p = 0.25	p = 0.02*	Strive
Infection and infestation	8	589	3356	348	2215	1.05 (0.93–1.19)	0	p = 0.43	p = 0.46
Administration site condition	6	229	2773	157	1922	1.74 (1.33–2.28)	34	p < 0.001*		HALO-EM
General and other	5	87	2723	42	1896	1.35 (0.80–2.26)	44	p = 0.26	p = 0.02*	Strive

Topiramate						Primary analysis
Cognitive	5	508	1281	107	630	2.21 (1.84–2.64)	0	p < 0.001*	p = 0.03*
Sensory and pain	5	792	1281	59	630	8.01 (3.95–16.26)	84*	p < 0.001*	p < 0.001*
Gastrointestinal	5	213	1281	63	630	1.66 (1.16–2.35)	36	p = 0.005*	p = 0.10
Infection and infestation	2	67	316	51	258	1.20 (0.87–1.65)	0	p = 0.28	p = 0.46
Administration site condition	N/A
General and other	5	321	1281	87	630	2.40 (1.24–4.67)	86*	p = 0.010*	p = 0.13

Topiramate						Sensitivity analysis
Cognitive	8	68	3356	35	2215	2.21 (1.84–2.64)	0	p < 0.001*	p = 0.03*
Sensory and pain	4	684	1105	26	445	10.40 (7.14–15.14)	0	p < 0.001*	p < 0.001*	INTREPID
Gastrointestinal	6	61	2723	57	1896	1.66 (1.16–2.35)	36	p = 0.005*	p = 0.02*
Infection and infestation	8	589	3356	348	2215	1.20 (0.87–1.65)	0	p = 0.28	p = 0.46
Administration site condition	N/A
General and other	4	276	1105	38	445	3.00 (1.91–4.71)	48	p < 0.001*	p = 0.02*	INTREPID

AE adverse event, CGRP(R) calcitonin gene-related peptide (receptor), CI confidence interval, mAbs monoclonal antibodies, M-H Mantel-Haenszel

*indicate statistical significance of p < 0.05

^aComparison between CGRP(R) mAbs studies and topiramate studies