Comparison 2. Stratified by dose.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality at maximal follow‐up	29		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
1.1 Azathioprine versus no intervention	2	224	Odds Ratio (M‐H, Fixed, 95% CI)	0.56 [0.32, 0.98]
1.2 Chlorambucil versus no intervention	1	24	Odds Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 3.28]
1.3 Colchicine versus no intervention	2	122	Odds Ratio (M‐H, Fixed, 95% CI)	0.77 [0.32, 1.85]
1.4 Cyclosporin versus no intervention	3	390	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.51, 1.50]
1.5 D‐Penicillamine versus no intervention	5	423	Odds Ratio (M‐H, Fixed, 95% CI)	0.90 [0.57, 1.44]
1.6 Glucocorticosteroids versus no intervention	1	36	Odds Ratio (M‐H, Fixed, 95% CI)	0.64 [0.14, 2.92]
1.7 Malotilate versus no intervention	1	101	Odds Ratio (M‐H, Fixed, 95% CI)	2.0 [0.47, 8.48]
1.8 Methotrexate versus no intervention	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	8.83 [1.01, 76.96]
1.9 UDCA (low) versus no intervention	2	64	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.03, 3.47]
1.10 UDCA (moderate) versus no intervention	4	670	Odds Ratio (M‐H, Fixed, 95% CI)	1.05 [0.62, 1.77]
1.11 UDCA (low) versus UDCA (high)	1	106	Odds Ratio (M‐H, Fixed, 95% CI)	1.04 [0.06, 17.06]
1.12 UDCA (moderate) versus UDCA (high)	1	103	Odds Ratio (M‐H, Fixed, 95% CI)	0.36 [0.01, 9.05]
1.13 UDCA (low) plus colchicine versus UDCA (low)	1	84	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.13, 7.45]
1.14 UDCA (low) plus methotrexate versus UDCA (low)	1	25	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.15 UDCA (moderate) versus UDCA (low)	1	101	Odds Ratio (M‐H, Fixed, 95% CI)	0.35 [0.01, 8.72]
1.16 Bezafibrate plus UDCA (moderate) versus UDCA (moderate)	1	27	Odds Ratio (M‐H, Fixed, 95% CI)	9.67 [0.45, 207.78]
1.17 Colchicine plus UDCA (moderate) versus UDCA (moderate)	1	74	Odds Ratio (M‐H, Fixed, 95% CI)	5.28 [0.24, 113.87]
1.18 Methotrexate plus UDCA (moderate) versus UDCA (moderate)	1	265	Odds Ratio (M‐H, Fixed, 95% CI)	1.17 [0.55, 2.51]
1.19 Obeticholic acid (low) plus UDCA (moderate) versus UDCA (moderate)	1	216	Odds Ratio (M‐H, Fixed, 95% CI)	1.55 [0.06, 38.46]
2 Mortality (< 1 year)	9		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
2.1 Azathioprine versus no intervention	1	39	Odds Ratio (M‐H, Fixed, 95% CI)	0.58 [0.16, 2.10]
2.2 Colchicine versus no intervention	1	64	Odds Ratio (M‐H, Fixed, 95% CI)	0.86 [0.22, 3.33]
2.3 Cyclosporin versus no intervention	1	12	Odds Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 3.63]
2.4 D‐Penicillamine versus no intervention	1	189	Odds Ratio (M‐H, Fixed, 95% CI)	0.71 [0.35, 1.42]
2.5 UDCA (low) versus no intervention	1	18	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.6 UDCA (low) versus UDCA (high)	1	106	Odds Ratio (M‐H, Fixed, 95% CI)	1.04 [0.06, 17.06]
2.7 UDCA (moderate) versus UDCA (high)	1	103	Odds Ratio (M‐H, Fixed, 95% CI)	0.36 [0.01, 9.05]
2.8 Obeticholic acid (low) plus UDCA (moderate) versus UDCA (moderate)	1	216	Odds Ratio (M‐H, Fixed, 95% CI)	1.55 [0.06, 38.46]
2.9 UDCA (low) plus colchicine versus UDCA (low)	1	84	Odds Ratio (M‐H, Fixed, 95% CI)	1.0 [0.13, 7.45]
2.10 UDCA (low) plus methotrexate versus UDCA (low)	1	25	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.11 UDCA (moderate) versus UDCA (low)	1	101	Odds Ratio (M‐H, Fixed, 95% CI)	0.35 [0.01, 8.72]
3 Mortality (1 to 5 years)	20		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.1 Azathioprine versus no intervention	1	185	Odds Ratio (M‐H, Fixed, 95% CI)	0.56 [0.30, 1.04]
3.2 Chlorambucil versus no intervention	1	24	Odds Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 3.28]
3.3 Colchicine versus no intervention	1	58	Odds Ratio (M‐H, Fixed, 95% CI)	0.71 [0.22, 2.25]
3.4 Cyclosporin versus no intervention	2	378	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.54, 1.64]
3.5 D‐Penicillamine versus no intervention	4	234	Odds Ratio (M‐H, Fixed, 95% CI)	1.10 [0.59, 2.08]
3.6 Glucocorticosteroids versus no intervention	1	36	Odds Ratio (M‐H, Fixed, 95% CI)	0.64 [0.14, 2.92]
3.7 Malotilate versus no intervention	1	101	Odds Ratio (M‐H, Fixed, 95% CI)	2.0 [0.47, 8.48]
3.8 Methotrexate versus no intervention	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	8.83 [1.01, 76.96]
3.9 UDCA (low) versus no intervention	1	46	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.03, 3.47]
3.10 UDCA (moderate) versus no intervention	4	670	Odds Ratio (M‐H, Fixed, 95% CI)	1.05 [0.62, 1.77]
3.11 Bezafibrate plus UDCA (moderate) versus UDCA (moderate)	1	27	Odds Ratio (M‐H, Fixed, 95% CI)	9.67 [0.45, 207.78]
3.12 Colchicine plus UDCA (moderate) versus UDCA (moderate)	1	74	Odds Ratio (M‐H, Fixed, 95% CI)	5.28 [0.24, 113.87]
3.13 Methotrexate plus UDCA (moderate) versus UDCA (moderate)	1	265	Odds Ratio (M‐H, Fixed, 95% CI)	1.17 [0.55, 2.51]
4 Serious adverse events (proportion)	12		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.1 Colchicine versus no intervention	1	64	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 D‐Penicillamine versus no intervention	1	52	Odds Ratio (M‐H, Fixed, 95% CI)	28.77 [1.57, 526.67]
4.3 Obeticholic acid (high) versus no intervention	1	79	Odds Ratio (M‐H, Fixed, 95% CI)	5.14 [0.57, 46.17]
4.4 Obeticholic acid (low) versus no intervention	1	76	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 8.22]
4.5 Obeticholic acid (moderate) versus no intervention	1	86	Odds Ratio (M‐H, Fixed, 95% CI)	0.79 [0.05, 13.01]
4.6 UDCA (low) versus no intervention	1	18	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.7 UDCA (moderate) versus no intervention	2	362	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.8 UDCA (low) versus bezafibrate	1	24	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.9 Obeticholic acid (low) versus obeticholic acid (high)	1	79	Odds Ratio (M‐H, Fixed, 95% CI)	0.09 [0.00, 1.61]
4.10 Obeticholic acid (moderate) versus obeticholic acid (high)	1	89	Odds Ratio (M‐H, Fixed, 95% CI)	0.15 [0.02, 1.37]
4.11 Obeticholic acid (moderate) versus obeticholic acid (low)	1	86	Odds Ratio (M‐H, Fixed, 95% CI)	2.43 [0.10, 61.39]
4.12 Lamivudine plus zidovudine plus UDCA (moderate) versus UDCA (moderate)	1	59	Odds Ratio (M‐H, Fixed, 95% CI)	0.47 [0.04, 5.43]
4.13 UDCA (moderate) versus obeticholic acid (low) plus UDCA (moderate)	1	216	Odds Ratio (M‐H, Fixed, 95% CI)	0.28 [0.08, 0.98]
4.14 Bezafibrate plus UDCA (low) versus UDCA (low)	1	22	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.15 UDCA (moderate) versus UDCA (low)	1	59	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.16 Colchicine plus UDCA (moderate) versus UDCA (moderate)	1	74	Odds Ratio (M‐H, Fixed, 95% CI)	3.08 [0.12, 78.14]
5 Serious adverse events (number of events)	1		Rate Ratio (Fixed, 95% CI)	Subtotals only
5.1 Obeticholic acid (low) plus UDCA (moderate) versus UDCA (moderate)	1		Rate Ratio (Fixed, 95% CI)	1.66 [0.75, 3.66]
6 Adverse events (proportion)	20		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
6.1 Cyclosporin versus no intervention	3	390	Odds Ratio (M‐H, Fixed, 95% CI)	3.04 [1.98, 4.68]
6.2 D‐Penicillamine versus no intervention	2	287	Odds Ratio (M‐H, Fixed, 95% CI)	4.51 [2.56, 7.93]
6.3 Malotilate versus no intervention	1	101	Odds Ratio (M‐H, Fixed, 95% CI)	11.43 [1.40, 93.04]
6.4 Obeticholic acid (high) versus no intervention	1	79	Odds Ratio (M‐H, Fixed, 95% CI)	16.6 [0.90, 305.59]
6.5 Obeticholic acid (low) versus no intervention	1	76	Odds Ratio (M‐H, Fixed, 95% CI)	1.59 [0.41, 6.17]
6.6 Obeticholic acid (moderate) versus no intervention	1	86	Odds Ratio (M‐H, Fixed, 95% CI)	8.81 [1.01, 76.73]
6.7 UDCA (low) versus no intervention	1	18	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.8 UDCA (moderate) versus no intervention	2	362	Odds Ratio (M‐H, Fixed, 95% CI)	1.45 [0.50, 4.25]
6.9 Glucocorticosteroids plus UDCA (moderate) versus azathioprine plus UDCA (moderate)	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	0.40 [0.08, 2.12]
6.10 UDCA (low) versus bezafibrate	1	24	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.11 Obeticholic acid (low) versus obeticholic acid (high)	1	79	Odds Ratio (M‐H, Fixed, 95% CI)	0.09 [0.00, 1.78]
6.12 Obeticholic acid (moderate) versus obeticholic acid (high)	1	89	Odds Ratio (M‐H, Fixed, 95% CI)	0.38 [0.02, 9.62]
6.13 Obeticholic acid (moderate) versus obeticholic acid (low)	1	86	Odds Ratio (M‐H, Fixed, 95% CI)	5.53 [0.59, 51.70]
6.14 Bezafibrate plus UDCA (low) versus UDCA (low)	1	22	Odds Ratio (M‐H, Fixed, 95% CI)	3.29 [0.12, 89.81]
6.15 Colestilan plus UDCA (low) versus UDCA (low)	1	11	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.16 Methotrexate plus UDCA (low) versus UDCA (low)	1	25	Odds Ratio (M‐H, Fixed, 95% CI)	115.0 [4.98, 2657.48]
6.17 UDCA (moderate) versus UDCA (low)	1	59	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6.18 Azathioprine plus UDCA (moderate) versus UDCA (moderate)	1	42	Odds Ratio (M‐H, Fixed, 95% CI)	19.67 [0.94, 413.50]
6.19 Colchicine plus UDCA (moderate) versus UDCA (moderate)	2	42	Odds Ratio (M‐H, Fixed, 95% CI)	6.20 [0.63, 60.80]
6.20 Glucocorticosteroids plus UDCA (moderate) versus UDCA (moderate)	2	135	Odds Ratio (M‐H, Fixed, 95% CI)	5.54 [1.35, 22.84]
6.21 TauroUDCA (moderate) versus UDCA (moderate)	1	30	Odds Ratio (M‐H, Fixed, 95% CI)	21.0 [2.16, 204.61]
7 Adverse events (number)	15		Rate Ratio (Fixed, 95% CI)	Subtotals only
7.1 Chlorambucil versus no intervention	1		Rate Ratio (Fixed, 95% CI)	3.67 [1.04, 12.87]
7.2 Cyclosporin versus no intervention	3		Rate Ratio (Fixed, 95% CI)	1.87 [1.51, 2.32]
7.3 D‐Penicillamine versus no intervention	3		Rate Ratio (Fixed, 95% CI)	2.64 [1.78, 3.91]
7.4 Malotilate versus no intervention	1		Rate Ratio (Fixed, 95% CI)	6.13 [1.38, 27.14]
7.5 Obeticholic acid (high) versus no intervention	1		Rate Ratio (Fixed, 95% CI)	1.91 [1.50, 2.44]
7.6 Obeticholic acid (low) versus no intervention	1		Rate Ratio (Fixed, 95% CI)	1.05 [0.80, 1.39]
7.7 Obeticholic acid (moderate) versus no intervention	1		Rate Ratio (Fixed, 95% CI)	1.25 [0.97, 1.62]
7.8 Obeticholic acid (low) versus obeticholic acid (high)	1		Rate Ratio (Fixed, 95% CI)	0.55 [0.43, 0.70]
7.9 Obeticholic acid (moderate) versus obeticholic acid (high)	1		Rate Ratio (Fixed, 95% CI)	0.66 [0.53, 0.81]
7.10 Obeticholic acid (moderate) versus obeticholic acid (low)	1		Rate Ratio (Fixed, 95% CI)	1.19 [0.93, 1.53]
7.11 UDCA (low) versus UDCA (high)	1		Rate Ratio (Fixed, 95% CI)	2.08 [0.78, 5.53]
7.12 UDCA (moderate) versus UDCA (high)	1		Rate Ratio (Fixed, 95% CI)	0.73 [0.21, 2.60]
7.13 UDCA (low) plus methotrexate versus UDCA (low)	1		Rate Ratio (Fixed, 95% CI)	30.64 [1.84, 510.76]
7.14 UDCA (moderate) versus UDCA (low)	1		Rate Ratio (Fixed, 95% CI)	0.35 [0.11, 1.10]
7.15 Azathioprine plus glucocorticosteroids plus UDCA (moderate) versus UDCA (moderate)	1		Rate Ratio (Fixed, 95% CI)	1.32 [0.88, 1.97]
7.16 Bezafibrate plus UDCA (moderate) versus UDCA (moderate)	1		Rate Ratio (Fixed, 95% CI)	11.79 [0.65, 213.14]
7.17 Colchicine plus UDCA (moderate) versus UDCA (moderate)	1		Rate Ratio (Fixed, 95% CI)	5.91 [0.28, 123.08]
7.18 TauroUDCA (moderate) versus UDCA (moderate)	1		Rate Ratio (Fixed, 95% CI)	1.17 [0.81, 1.71]
8 Liver transplantation	12		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
8.1 Cyclosporin versus no intervention	2	378	Odds Ratio (M‐H, Fixed, 95% CI)	0.86 [0.43, 1.72]
8.2 D‐Penicillamine versus no intervention	1	189	Odds Ratio (M‐H, Fixed, 95% CI)	0.93 [0.06, 15.05]
8.3 Methotrexate versus no intervention	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.17 [0.02, 1.58]
8.4 UDCA (low) versus no intervention	2	162	Odds Ratio (M‐H, Fixed, 95% CI)	0.99 [0.24, 4.06]
8.5 UDCA (moderate) versus no intervention	3	478	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.44, 1.76]
8.6 UDCA (low) versus UDCA (high)	1	106	Odds Ratio (M‐H, Fixed, 95% CI)	3.17 [0.13, 79.71]
8.7 UDCA (moderate) versus UDCA (high)	1	103	Odds Ratio (M‐H, Fixed, 95% CI)	3.37 [0.13, 84.70]
8.8 UDCA (moderate) versus UDCA (low)	1	101	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.06, 17.47]
8.9 Bezafibrate plus UDCA (moderate) versus UDCA (moderate)	1	27	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8.10 Methotrexate plus UDCA (moderate) versus UDCA (moderate)	1	265	Odds Ratio (M‐H, Fixed, 95% CI)	0.70 [0.35, 1.39]
9 Decompensated liver disease	7		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
9.1 D‐Penicillamine versus no intervention	1	24	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 UDCA (moderate) versus no intervention	2	351	Odds Ratio (M‐H, Fixed, 95% CI)	1.33 [0.84, 2.12]
9.3 Obeticholic acid (low) plus UDCA (moderate) versus UDCA (moderate)	1	216	Odds Ratio (M‐H, Fixed, 95% CI)	1.55 [0.06, 38.46]
9.4 UDCA (low) plus colchicine versus UDCA (low)	1	84	Odds Ratio (M‐H, Fixed, 95% CI)	0.21 [0.04, 1.07]
9.5 Azathioprine plus UDCA (moderate) versus UDCA (moderate)	1	42	Odds Ratio (M‐H, Fixed, 95% CI)	0.52 [0.05, 5.18]
9.6 Glucocorticosteroids plus UDCA (moderate) versus UDCA (moderate)	1	66	Odds Ratio (M‐H, Fixed, 95% CI)	0.55 [0.11, 2.69]
9.7 Methotrexate plus UDCA (moderate) versus UDCA (moderate)	1	151	Odds Ratio (M‐H, Fixed, 95% CI)	2.00 [0.79, 5.04]
9.8 Glucocorticosteroids plus UDCA (moderate) versus azathioprine plus UDCA (moderate)	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.10, 11.18]
10 Cirrhosis	3		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
10.1 Azathioprine versus no intervention	1	31	Odds Ratio (M‐H, Fixed, 95% CI)	0.79 [0.18, 3.41]
10.2 UDCA (low) versus no intervention	1	22	Odds Ratio (M‐H, Fixed, 95% CI)	0.15 [0.01, 1.53]
10.3 Azathioprine plus glucocorticosteroids plus UDCA (moderate) versus UDCA (moderate)	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	0.28 [0.03, 2.90]