Table 2.

Effect of treatment on each specific grade 1-5 adverse event. Values are odds ratios* unless stated otherwise

Group	Fatigue	Pruritus	Rash	Diarrhoea	Colitis	Nausea	Vomiting	ALT increased	AST increased	Pneumonitis	CRE increased	Hypothyroidism	Hyperthyroidism	Arthralgia
No of studies	26	24	24	27	16	26	19	16	16	14	10	19	14	17
No of patients	13 641	12 371	12 371	14 139	8729	13 641	9761	7666	7666	6855	4585	9252	7562	9762
Nivolumab as control
Ipilimumab	1.14	0.48	0.69	0.42	0.17	0.75	0.43	0.63	0.68	1.02	0.33	2.68	2.58	1.96
Tremelimumab	0.84	0.55	0.24	0.15	0.99	0.61	0.52	NA	NA	NA	NA	1.49	0.72	NA
Pembrolizumab	1.22	0.82	0.87	0.93	0.66	0.88	1.09	0.47	0.49	0.37	1.85	0.96	1.12	0.60
Atezolizumab	1.26	1.21	1.13	1.28	NA	0.61	0.49	NA	NA	0.58	NA	0.67	NA	0.82
Two ICI drugs	0.95	0.43	0.47	0.29	0.13	0.48	0.29	0.12	0.15	0.24	0.10	0.73	0.32	0.96
One ICI drug with conventional therapy	0.55	0.79	0.47	0.31	0.24	0.23	0.28	0.49	0.72	0.19	0.71	3.73	1.53	0.55
Conventional therapy	0.70	4.76	2.19	0.76	4.80	0.31	0.38	1.58	1.86	2.26	1.14	15.69	7.58	0.77
Ipilimumab as control
Tremelimumab	0.75	1.15	0.36	0.37	5.66	0.82	1.20	NA	NA	NA	NA	0.56	0.28	NA
Pembrolizumab	1.08	1.71	1.28	2.24	3.79	1.17	2.53	0.74	0.72	0.37	5.63	0.36	0.44	0.31
Atezolizumab	1.11	2.49	1.65	3.08	NA	0.82	1.14	NA	NA	0.57	NA	0.25	NA	0.42
Two ICI drugs	0.84	0.90	0.68	0.70	0.74	0.65	0.67	0.19	0.22	0.24	0.32	0.27	0.13	0.49
One ICI drug with conventional therapy	0.48	1.65	0.68	0.74	1.37	0.31	0.64	0.77	1.06	0.19	2.05	1.38	0.59	0.28
Conventional therapy	0.62	9.95	3.20	1.83	27.91	0.42	0.88	2.51	2.74	2.23	3.47	5.84	2.92	0.40
Tremelimumab as control
Pembrolizumab	1.44	1.48	3.56	6.04	0.65	1.45	2.07	NA	NA	NA	NA	0.65	1.57	NA
Atezolizumab	1.48	2.16	4.64	8.32	NA	1.00	0.94	NA	NA	NA	NA	0.45	NA	NA
Two ICI drugs	1.12	0.78	1.91	1.89	0.13	0.80	0.56	NA	NA	NA	NA	0.50	0.44	NA
One ICI drug with conventional therapy	0.65	1.43	1.92	1.99	0.24	0.38	0.53	NA	NA	NA	NA	2.51	2.11	NA
Conventional therapy	0.83	8.63	8.93	4.96	5.04	0.51	0.73	NA	NA	NA	NA	10.58	10.57	NA
Pembrolizumab as control
Atezolizumab	1.03	1.47	1.29	1.37	NA	0.69	0.45	NA	NA	1.57	NA	0.69	NA	1.35
Two ICI drugs	0.78	0.53	0.53	0.31	0.19	0.55	0.27	0.26	0.31	0.64	0.06	0.76	0.28	1.58
One ICI drug with conventional therapy	0.45	0.97	0.54	0.33	0.36	0.26	0.25	1.04	1.48	0.53	0.38	3.85	1.35	0.92
Conventional therapy	0.57	5.79	2.50	0.82	7.36	0.36	0.35	3.38	3.81	6.06	0.62	16.21	6.71	1.29
Atezolizumab as control
Two ICI drugs	0.75	0.36	0.41	0.23	NA	0.80	0.59	NA	NA	0.42	NA	1.12	NA	1.18
One ICI drug with conventional therapy	0.43	0.66	0.41	0.24	NA	0.38	0.56	NA	NA	0.33	NA	5.57	NA	0.68
Conventional therapy	0.56	3.96	1.93	0.59	NA	0.51	0.77	NA	NA	3.91	NA	23.47	NA	0.95
Two ICI drugs as control
One ICI drug with conventional therapy	0.57	1.83	1.00	1.06	1.89	0.48	0.95	4.03	4.76	0.79	6.67	5.01	4.75	0.58
Conventional therapy	0.74	10.97	4.69	2.62	38.41	0.64	1.30	13.15	12.38	9.41	11.00	21.54	23.79	0.81
One ICI drug with conventional therapy as control
Conventional therapy	1.28	5.99	4.68	2.48	20.80	1.33	1.38	3.24	2.59	11.51	1.69	4.25	4.94	1.40

ALT=alanine transaminase; AST=aspartate transaminase; CRE=blood creatinine; ICI=immune checkpoint inhibitor; NA=not applicable.

^*Significant values are shown in italics.