Table 1.
Overview of study characteristics of included studies
| Study | Interventions | Study design | PBC, N (%) PSC, N (%) |
Age, years | Female gender, n (%) |
Treatment duration | Main efficacy endpoint | Concomitant medications |
|---|---|---|---|---|---|---|---|---|
| Anion-exchange resins (n = 8) | ||||||||
| Datta 1966 [40] | Cholestyramine | OL |
20 (100) 0 |
47.6 (mean) | 24 (88.9) of total (n = 27) | 32 months (mean) | Pruritus reduction | NR |
| Van Berge Henegouwen 1974 [62] | Cholestyramine | Prospective, OL |
6 (75) 1 (12.5) |
NR | NR | 5 weeks | NRS; pruritus reduction | Immunosuppressive therapy (n = 6 patients) |
| Duncan 1984 [41] | Cholestyramine vs terfenadine vs chlorpheniramine vs placebo | RCT, SB, CO, PC, SC |
7 (87.5) 1 (12.5) |
NR | NR | 2 weeks | NRS | No antipruritic medication |
| Floreani 1988 [42] | DEAE-dextran vs placebo | RCT, DB, CO, PC |
12 (100) 0 |
NR | 12 (100) | 15 days | Pruritus reduction | NR |
| Zuin 1991 [67] | Cholestyramine vs DEAE-dextran | RCT, OL, PG |
30 (100) 0 |
NR | NR | 2 months | NRS; pruritus reduction | NR |
| Taha 1994 [57] | Cholestyramine 4 g BID vs no treatment vs UDCA vs cholestyramine + UDCA | OL, sequential CO |
8 (100) 0 |
52 (median) | 8 (100) |
2 weeks (4 phases) |
VAS | UDCA |
| Yokomori 2001 [15] | Colestilan vs no treatment | RCT, OL, PG, SC |
11 (100) 0 |
53.6 (mean) | 9 (81.1) | 4 weeks | NRS | No antipruritic medication |
| Kuiper 2010 [45] | Colesevelam vs placebo | RCT, DB, PG, PC, MC |
14 (40) 14 (40) |
52 (mean) | 22 (62.9) of total (n = 35) | 21 days | Pruritus reduction; VAS | UDCA, naltrexone (n = 2 patients) |
| Antibiotics (n = 8) | ||||||||
| Ghent 1988 [43] | Rifampicin vs placebo | RCT, DB, CO, PC, SC |
9 (100) 0 |
57.4 (mean) | 8 (88.9) |
2 weeks (4 cycles) |
VAS | Cholestyramine |
| Bachs 1989 [35] | Rifampicin vs phenobarbitone | RCT, CO, SC |
22 (100) 0 |
49.7 [8.4] (mean [SD]) | 22 (100) | 2 weeks | NRS; pruritus reduction | No antipruritic medication |
| Podesta 1991 [53] | Rifampicin vs placebo | RCT, DB, CO, PC, MC |
14 (100) 0 |
43 (mean) | 13 (92.9) | 1 week | Pruritus reduction; VAS | No antipruritic medication |
| Podesta 1991 [53] | Rifampicin | OL |
18 (100) 0 |
32 − 72 (range) | Pruritus reduction; VAS | No antipruritic medication | ||
| Bachs 1992 [36] | Rifampicin | Prospective, OL, SC |
16 (100) 0 |
49.7 (mean) | 16 (100) | 11.7 months (mean) | NRS; pruritus reduction | No antipruritic medication |
| Loginov 1993 [48] | Rifampicin | OL |
7 (100) 0 |
49.7 ± 2.7 | 7 (100) | 2 weeks | Pruritus reduction | Ion-exchange resins |
| Tabibian 2017 [56] | Rifaximin | Prospective, OL, SC |
0 (0) 16 (100) |
40 (median) | 3 (19) | 12 weeks | 5-D itch scale; fatigue | NR |
| Webb 2018 [64] | Rifampicin | Retrospective, OL, SC |
36 (34.3) 44 (41.9) |
Hepatitis: 37 [28–43] (median [IQR]) No hepatitis: |
Hepatitis: 3 (60) No hepatitis: 62 (62) |
131 days (median) | NR | UDCA, proton pump inhibitors, cholestyramine, antibiotics, 5-aminosalicylic acid preps, azathioprine or 6-mercaptopurine, antihistamines, prednisolone, statins, sertraline, naltrexone |
| Oral opiate agents (n = 7) | ||||||||
| Summerfield 1980 [55] | Naloxone vs placebo | RCT, DB, CO, PC |
NR NR |
n = 20 with cholestatic liver disease (29–71 range) |
13 (65) | 1 night | VAS; scratching activity | Cholestyramine |
| Thornton 1988 [59] | Nalmefene | Prospective, OL, SC |
9 (100) 0 |
57.2 (average) | 8 (88.9) | 6 months | VAS; fatigue | No antipruritic medication |
| Bergasa 1992 [37] | Naloxone vs placebo | SB, CO, PC |
8 (100) 0 |
50 (average) | 8 (100) | 24 h | VAS; scratching activity | No antipruritic medication |
| Wolfhagen 1997 [65] | Naltrexone vs placebo | RCT, DB, PG, PC, SC |
13 (81.3) 3 (18.8) |
52 (median) | 12 (75) | 4 weeks | VAS; interference of itch on sleep; fatigue | No antipruritic medication |
| Terg 2002 [58] | Naltrexone vs placebo | RCT, DB, CO, PC, MC |
15 (75) 1 (5) |
55 (mean) | 17 (85) | 2 weeks | Pruritus reduction; VAS | UDCA, antipruritic medication |
| Terg 2002 [58] | Naltrexone | OL | 9 | 36 − 70 (range) | 2 months | Pruritus reduction; VAS | UDCA, antipruritic medication | |
| Yagi 2018 [66] | Nalfurafine | Prospective, OL, MC |
44 (100) 0 |
66.8 (mean) | 39 (88.6) | 12 weeks |
VAS; PBC-40/ PBC-27 itch |
UDCA, bezafibrate, anti-pruritic medication |
| Selective serotonin reuptake inhibitors (n = 2) | ||||||||
| Mayo 2007 [49] | Sertraline vs placebo | RCT, DB, CO, PC, SC |
18 (75) 4 (16.7) |
NR | 28 (84.5) | 6 weeks | Pruritus reduction; VAS; interference of itch on sleep | UDCA |
| Ataei 2019 [34] | Sertraline vs rifampicin | RCT, SB, PG, SC |
13 (36.1) 23 (63.9) |
41.6 (mean) | 16 (44.4) | 4 weeks | VAS | UDCA |
| Fibrate (n = 6) | ||||||||
| Kanda 2003 [44] |
Bezafibrate vs no treatment |
RCT, OL, PG, SC |
22 (100) 0 |
56 (mean) for total (n = 22) | 19 (86.4) | 6 months | N/A | UDCA |
| Levy 2011 [47] | Fenofibrate | OL, MC |
20 (100) 0 |
56 (median) | 16 (80) | 48 weeks | Pruritus reduction | UDCA |
| Reig 2018 [54] |
Bezafibrate vs no treatment |
Prospective, OL, SC |
48 (100) 0 |
53.1 (mean) | 45 (94) | 38 months (median) | Pruritus reduction; VAS; 5-D itch scale | UDCA |
| Corpechot 2018 [39] | Bezafibrate vs placebo | RCT, DB, PG, PC, MC |
100 (100) 0 |
53 (mean) | 95 (95) | 24 months | VAS; fatigue | UDCA |
| Lemoinne 2018 [46] | Fibrate (bezafibrate and fenofibrate) | Retrospective, MC |
0 (0) 20 (100) |
43.8 (median) | 5 (25) | 4.1 years (median) | NRS; pruritus reduction | UDCA |
| de Vries 2019 [68] | Bezafibrate vs placebo | RCT, DB, PC, PG, MC |
26 (35.1) 46 (62.1) |
46 (median, bezafibrate group) 50 (median, placebo group) |
45 (60.8) | 3 weeks | Pruritus reduction | UDCA, bile acid sequestrants |
| IBAT inhibitors (n = 3) | ||||||||
| Hegade 2017 [23] | Linerixibat vs placebo | RCT, DB, CO, PC, MC |
22 (100) 0 |
52.9 (mean) | 19 (86) | 2 weeks |
NRS; PBC-40/ PBC-27 itch; 5-D itch scale; interference of itch on sleep |
UDCA |
| Al-Dury 2018 [21] | A4250/odevixibat | OL, SC |
10 (100) 0 |
54.9 (mean) | 9 (90) | 4 weeks |
PBC-40/ PBC-27 itch |
UDCA |
| Mayo 2019 [24] | Maralixibat vs placebo | RCT, DB, PG, PC, MC |
66 (100) 0 |
53.1 (mean) | 60 (92.0) | 13 weeks |
Itch RO; PBC-40/PBC-27 itch; 5-D itch scale; interference of itch on sleep |
UDCA |
| Other (n = 8) | ||||||||
| Bloomer 1975 [38] | Phenobarbital | Prospective, OL |
7 (77.8) 2 (22.2) |
32.3 (for n = 15) (average) |
10 (66.7) | 1–5 months | NRS | Cholestyramine |
| Turner 1990 [60] | Flumecinol vs placebo | RCT, DB, PG, PC |
38 (92.7) NR |
NR | NR | 3 weeks | VAS | Cholestyramine |
| Turner 1994 (LD) [61] | Flumecinol vs placebo | RCT, DB, PG, PC |
46 (92) NR |
NR | 47 (94) | 3 weeks | Pruritus reduction; VAS | Antipruritic medication |
| Turner 1994 (HD) [61] | Flumecinol vs placebo | RCT, DB, PG, PC |
19 (100) 0 |
NR | NR | 3 weeks | Pruritus reduction; VAS | Cholestyramine |
| Villamil 2005 [63] | Lidocaine vs placebo | RCT, DB, PG, PC, SC |
13 (72.2) 4 (22.2) |
46.5 (mean) | 14 (77.8) | 7 days | VAS; fatigue | UDCA |
| O'Donohue 2005 [52] | Ondansetron vs placebo | RCT, DB, PG, PC |
17 (89.5) 0 (0) |
55.1 (mean) | 16 (84.2) | 5 days | Pruritus reduction; VAS; scratching activity | No anti-pruritics, no UDCA |
| Mayo 2018 [50] | NGM282 vs placebo | RCT, DB, PG, PC, MC |
45 (100) 0 |
56.2 (mean) | 41 (91.1) | 28 days | Pruritus reduction; VAS; 5-D itch scale | UDCA |
| Mayo 2019 [51] | NGM282 vs placebo | RCT, DB, PG, PC, MC |
0 (0) 62 (100) |
NR | NR | 12 weeks | NRS; 5-D itch scale | NR |
CO, crossover; DB, double-blind; DEAE, diethylaminoethyl; IBAT, ileal bile acid transporter; MC, multicentre; N/A, not applicable; NR, not reported; NRS, numerical rating scale; OL, open-label; PBC, primary biliary cholangitis; PC, placebo-controlled; PG, parallel group; PSC, primary sclerosing cholangitis; RCT, randomised controlled trial; SB, single blind; SC, single centre; UDCA, ursodeoxycholic acid; VAS, visual analogue scale