Comparison 6. Secondary outcome ‐ adverse events.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Non‐biological treatments versus placebo	4	1023	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.78, 1.50]
6.1.1 Methotrexate versus placebo	3	319	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.81, 1.10]
6.1.2 Fumaric acid esters versus placebo	1	704	Risk Ratio (M‐H, Random, 95% CI)	1.40 [1.22, 1.62]
6.2 Non‐biological treatment 1 versus non‐biological treatment 2	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
6.2.1 Ciclosporin versus methotrexate	2	172	Risk Ratio (M‐H, Random, 95% CI)	1.10 [0.90, 1.34]
6.2.2 Methotrexate versus fumaric acid esters	2	168	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.90, 1.24]
6.3 Anti‐TNF alpha versus placebo	27	9856	Risk Ratio (M‐H, Random, 95% CI)	1.06 [1.02, 1.10]
6.3.1 Etanercept versus placebo	11	4225	Risk Ratio (M‐H, Random, 95% CI)	1.08 [1.00, 1.16]
6.3.2 Adalimumab versus placebo	9	3338	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.99, 1.12]
6.3.3 Certolizumab versus placebo	4	1026	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.86, 1.09]
6.3.4 Infliximab versus placebo	4	1267	Risk Ratio (M‐H, Random, 95% CI)	1.12 [0.93, 1.36]
6.4 Ustekinumab versus placebo	11	4596	Risk Ratio (M‐H, Random, 95% CI)	1.07 [1.01, 1.13]
6.5 Anti‐IL17 versus placebo	21	11333	Risk Ratio (M‐H, Random, 95% CI)	1.21 [1.11, 1.30]
6.5.1 Secukinumab versus placebo	11	3706	Risk Ratio (M‐H, Random, 95% CI)	1.20 [1.06, 1.36]
6.5.2 Ixekizumab versus placebo	4	3268	Risk Ratio (M‐H, Random, 95% CI)	1.24 [1.07, 1.45]
6.5.3 Brodalumab versus placebo	5	4109	Risk Ratio (M‐H, Random, 95% CI)	1.15 [1.00, 1.32]
6.5.4 Bimekizumab versus placebo	1	250	Risk Ratio (M‐H, Random, 95% CI)	1.70 [1.11, 2.58]
6.6 Anti‐IL23 versus placebo	14	5882	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.87, 1.00]
6.6.1 Guselkumab versus placebo	5	1767	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.90, 1.11]
6.6.2 Tildrakizumab versus placebo	3	1904	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.72, 1.02]
6.6.3 Risankizumab versus placebo	4	1476	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.77, 1.07]
6.6.4 Mirikizumab versus placebo	2	735	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.83, 1.19]
6.7 Biologic versus non‐biological treatments	9		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
6.7.1 Infliximab versus methotrexate	1	868	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.97, 1.20]
6.7.2 Adalimumab versus methotrexate	1	218	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.78, 1.05]
6.7.3 Secukinumab versus fumaric acid esters	1	202	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.71, 0.94]
6.7.4 Etanercept versus acitretin	2	82	Risk Ratio (M‐H, Random, 95% CI)	1.19 [0.72, 1.96]
6.7.5 Ixekizumab versus fumaric acid esters	1	108	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.74, 1.21]
6.7.6 Ixekizumab versus methotrexate	1	108	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.76, 1.25]
6.7.7 Guselkumab versus fumaric acid esters	1	119	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.65, 0.89]
6.7.8 Risankizumab versus fumaric acid esters	1	120	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.70, 0.99]
6.7.9 Brodalumab versus fumaric acid esters	1	210	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.62, 0.87]
6.8 Biologic 1 versus biologic 2	21		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
6.8.1 Ustekinumab versus etanercept	1	903	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.89, 1.06]
6.8.2 Secukinumab versus etanercept	1	980	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.89, 1.12]
6.8.3 Ixekizumab versus etanercept	2	2209	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.97, 1.15]
6.8.4 Infliximab versus etanercept	1	48	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.86, 1.08]
6.8.5 Tildrakizumab versus etanercept	1	934	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.65, 0.86]
6.8.6 Certolizumab versus etanercept	1	502	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.86, 1.28]
6.8.7 Secukinumab versus ustekinumab	2	1778	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.98, 1.16]
6.8.8 Ixekizumab versus ustekinumab	1	302	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.93, 1.13]
6.8.9 Brodalumab versus ustekinumab	2	3088	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.93, 1.09]
6.8.10 Risankizumab versus ustekinumab	3	965	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.85, 1.11]
6.8.11 Guselkumab versus adalimumab	3	1658	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.89, 1.09]
6.8.12 Risankizumab versus adalimumab	1	605	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.82, 1.43]
6.8.13 Ixekizumab versus guselkumab	1	1027	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.92, 1.15]
6.8.14 Risankizumab versus secukinumab	1	327	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.87, 1.15]
6.9 Small molecules versus placebo	14	5785	Risk Ratio (M‐H, Random, 95% CI)	1.25 [1.14, 1.38]
6.9.1 Apremilast versus placebo	7	2593	Risk Ratio (M‐H, Random, 95% CI)	1.24 [1.13, 1.36]
6.9.2 Tofacitinib versus placebo	6	2925	Risk Ratio (M‐H, Random, 95% CI)	1.28 [1.01, 1.63]
6.9.3 TYK2 versus placebo	1	267	Risk Ratio (M‐H, Random, 95% CI)	1.31 [0.97, 1.77]
6.10 Biologic versus small molecules	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
6.10.1 Etanercept versus tofacitinib	1	998	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.89, 1.12]
6.10.2 Etanercept versus apremilast	1	166	Risk Ratio (M‐H, Random, 95% CI)	1.32 [1.03, 1.69]