Comparison 2. Change in number of HAE attacks per week.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Change in number of HAE attacks per week by drug	11		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.1.1 Avoralstat	2	158	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.37, 0.18]
2.1.2 Berotralstat	3	217	Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.45, ‐0.17]
2.1.3 C1‐INH(SC)	1	180	Mean Difference (IV, Random, 95% CI)	‐0.83 [‐0.98, ‐0.67]
2.1.4 pdC1‐INH	1	113	Mean Difference (IV, Random, 95% CI)	‐0.53 [‐0.58, ‐0.48]
2.1.5 C1‐INH‐nf	1	44	Mean Difference (IV, Random, 95% CI)	‐0.53 [‐0.78, ‐0.28]
2.1.6 rhC1‐INH	1	96	Mean Difference (IV, Random, 95% CI)	‐0.92 [‐1.31, ‐0.53]
2.1.7 lanadelumab	2	140	Mean Difference (IV, Random, 95% CI)	‐0.38 [‐0.45, ‐0.32]
2.2 Change in number of HAE attacks per week by drug (approved doses only)	11		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.2.1 Avoralstat (not approved)	2	158	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.37, 0.18]
2.2.2 Berotralstat	3	130	Mean Difference (IV, Random, 95% CI)	‐0.39 [‐0.74, ‐0.05]
2.2.3 C1‐INH(SC)	1	90	Mean Difference (IV, Random, 95% CI)	‐0.81 [‐0.98, ‐0.64]
2.2.4 C1‐INH‐nf	1	44	Mean Difference (IV, Random, 95% CI)	‐0.53 [‐0.78, ‐0.28]
2.2.5 pdC1‐INH (not approved)	1	113	Mean Difference (IV, Random, 95% CI)	‐0.53 [‐0.58, ‐0.48]
2.2.6 rhC1‐INH (not approved)	1	96	Mean Difference (IV, Random, 95% CI)	‐0.92 [‐1.31, ‐0.53]
2.2.7 Lanadelumab	2	83	Mean Difference (IV, Random, 95% CI)	‐0.41 [‐0.48, ‐0.35]
2.3 Change in number of HAE attacks per week by dose (avoralstat)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.3.1 300 mg 3 times/day	1	54	Mean Difference (IV, Random, 95% CI)	0.09 [‐0.10, 0.28]
2.3.2 400 mg 3 times/day	1	48	Mean Difference (IV, Random, 95% CI)	‐0.45 [‐0.75, ‐0.15]
2.3.3 500 mg 3 times/day	1	56	Mean Difference (IV, Random, 95% CI)	0.00 [‐0.19, 0.19]
2.4 Change in number of HAE attacks per week by dose (berotralstat)	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.4.1 < 100 mg	1	30	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.40, 0.20]
2.4.2 100–149 mg	3	130	Mean Difference (IV, Random, 95% CI)	‐0.35 [‐0.74, 0.05]
2.4.3 150 mg	2	93	Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.37, ‐0.05]
2.4.4 250 mg	1	38	Mean Difference (IV, Random, 95% CI)	‐0.42 [‐0.65, ‐0.19]
2.4.5 350 mg	1	41	Mean Difference (IV, Random, 95% CI)	‐0.43 [‐0.64, ‐0.22]
2.5 Change in number of HAE attacks per week by dose (C1‐INH – all forms)	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.5.1 2000 IU twice per week	1	113	Mean Difference (IV, Random, 95% CI)	‐0.53 [‐0.58, ‐0.48]
2.5.2 1000 IU twice per week	1	44	Mean Difference (IV, Random, 95% CI)	‐0.53 [‐0.78, ‐0.28]
2.5.3 60 IU/kg twice per week	1	90	Mean Difference (IV, Random, 95% CI)	‐0.81 [‐0.98, ‐0.64]
2.5.4 50 IU/kg twice per week	1	64	Mean Difference (IV, Random, 95% CI)	‐1.11 [‐1.52, ‐0.70]
2.5.5 50 IU/kg once per week	1	64	Mean Difference (IV, Random, 95% CI)	‐0.71 [‐1.16, ‐0.26]
2.5.6 40 IU/kg twice per week	1	90	Mean Difference (IV, Random, 95% CI)	‐1.01 [‐1.58, ‐0.44]
2.6 Change in number of HAE attacks per week by dose (lanadelumab)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.6.1 150 mg every 4 weeks	1	69	Mean Difference (IV, Random, 95% CI)	‐0.37 [‐0.46, ‐0.28]
2.6.2 300 mg every 4 weeks	1	70	Mean Difference (IV, Random, 95% CI)	‐0.36 [‐0.45, ‐0.27]
2.6.3 300 mg every 2 weeks	2	83	Mean Difference (IV, Random, 95% CI)	‐0.41 [‐0.48, ‐0.35]
2.7 Change in number of HAE attacks per week (C1‐INH) – head‐to‐head trials	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.7.1 C1‐INH high dose vs low dose (all forms)	3	153	Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.27, ‐0.02]
2.8 Change in number of HAE attacks per week (children and adolescents)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.8.1 Children (C1‐INH‐nf 1000 IU vs 500 IU)	1	24	Mean Difference (IV, Random, 95% CI)	‐0.12 [‐0.36, 0.12]
2.8.2 Adolescents (lanadelumab vs placebo)	1	9	Mean Difference (IV, Random, 95% CI)	‐0.14 [‐0.38, 0.10]