Table 1.
Characteristics of included studies—uncontrolled observational studies
| Study (reference no) | Intervention | Outcomes being evaluated | Disease duration | Total subjects enrolled | Gender (M:F) | Age of subjects | Follow-up duration | Children/adults/both |
|---|---|---|---|---|---|---|---|---|
| Shelhamer 1985 (32) | CYC | Clinical; Angio | 3 me | 7 | 0:7 | 23.57 ± 10.56 ya | NA | Both |
| Hoffman 1994 (33) | MTX | Clinical; Angio; relapse | 5.2 (1–12) yb | 18 | 3:15 | 30 (13–56) yb | 2.8 (1.3–4.8) yb | Both |
| Hahn 1998 (34) | CYC | Relapse | NA | 13 | NA | NA | NA | Children |
| Valsakumar 2003 (35) | AZA | Clinical; Angio; relapse | 12.9 ± 5.8 ma | 15 | 0:15 | 28.3 ± 7.3 ya | 1 y e | Both |
| de Franciscis 2007 (38) | MTX + CYC | Clinical; relapse; inflammatory | NA | 10 | 2:8 | 37.1 ± 4.1 ya | 5.5 (2–10) yc | Adults |
| Shinjo 2007 (39) | MMF | Clinical; ∆CS | 57.5 ± 65.8 ma | 10 | 3:7 | 29.9 ± 8.9 ya | 23.3 ± 12.1 ma | Adults |
| Goel 2010 (41) | MMF | Clinical; ∆CS | 35.5 ± 28.4 ma | 21 | 2:19 | 31.9 ± 13.8 ya | 9.6 ± 6.4 ma | Both |
| de Souza 2012 (42) | LEF | Clinical; Angio; ∆CS | 38 (29.1–73) md | 15 | 1:14 | 36.2 ± 12.6 ya | 9.1 ± 3 ma | Adults |
| Stern 2014 (53) | CYC | Clinical | 2.6 ± 2.4 ya | 16 | NA | NA | 12 (7–36) md | Children |
| Li 2016 (58) | MMF | Clinical; Angio; ∆CS | 12 (7.5–36) md | 30 | 3:27 | 24.5 (19.8,32) yd | 17 (11,28) md | NA |
| Ohigashi 2017 (64) | MTX, CsA, AZA, TAC | Clinical | 70.8 ± 40.8 ma | 44 | 3:41 | NA | NA | Both |
| Cui 2020 (82) | LEF | Clinical; Angio; relapse | NA | 56 | 14:42 | 31.85 ± 12.56 ya | 14.44 ± 6.86 ma | Both |
| Wei 2021 (97) | CYC | Clinical | 5.12 ± 7.26 ya | 71 | 7:64 | 29.44 ± 11.75 ya | 3.42 ± 2.38 ya | Both |
| Mustapha 2020 (99) | LEF | Clinical | NA | 9 | NA | NA | 24 me | NA |
| Li 2020 (86) | Tofacitinib | Clinical; Angio; ∆CS | 32.4 ± 25.5 ma | 5 | 0:5 | 22 ± 4.58 ya | 6 me | Both |
| Nakagomi 2018 (71) | Rituximab | Clinical; ∆CS; relapse | 5.5 yf | 8 | NA | 38 yf | 12 me | NA |
| Pazzola 2018 (75) | Rituximab | Clinical; Angio; PET; ∆CS | 4.8 ± 7.7 ya | 7 | 1:6 | 32.4 ± 17.3 ya | 32.57 ± 24.7 ma | Both |
| Hoffman 2004 (36) | TNFi (ETAN, IFX) | Clinical; Angio; ∆CS; relapse | 6.5 ye | 15 | 1:14 | 27.53 ± 9.32 ya | 20.67 ± 15.86 ma | Both |
| Baldissera 2007 (37) | TNFi (IFX, ADA,ETAN) | Angio; ∆CS | 52 (17–226) mc | 12 | 1:11 | 35 ± 10 ya | 15 (4–28) mc | NA |
| Molloy 2010 (40) | TNFi (IFX, ETAN) | Clinical; Angio; ∆CS; relapse | 116 (39–344) mc | 25 | 3:22 | 35 (15–64) yb |
IFX 28 (2–84) mc; ETAN 28 (4–82) mc |
Both |
| Mekinian 2012 (43) | TNFi (IFX) | Clinical; ∆CS | 37 (6–365) mc | 15 | 2:13 | 41 (17–61) yc | 43 (4–71) mc | Both |
| Quartuccio 2012 (44) | TNFi (IFX) | Clinical; Angio; inflammatory; ∆CS; relapse | 12 (0–96) mc | 15 | NA | 33.07 ± 14.54 ya | 74 ± 44 ma | Both |
| Schmidt 2012 (45) | TNFi IIFX, ADA,ETAN) | Clinical; Angio; relapse | 15.9 (2–32.7) md | 20 | 1:19 | 33 ± 10.2 ya | 23 (8.7–38.9) md | NA |
| Tombetti 2013 (48) | TNFi (IFX, ADA, GOL) | Clinical; Angio; ∆CS | NA | 15 | 0:15 | 36 ye | 46 (11–56) mb | NA |
| Serra 2014 (52) | TNFi (ADA, IFX) | Clinical; inflammatory | Enrolled at diagnosis | 5 | 1:4 | 36.6 ± 2.41 ya | 1 ye | Adults |
| Youngstein 2014 (54) | TNFi (IFX, ADA,ETAN) | Clinical; Angio; ∆CS; relapse | NA | 8 | 1:7 | 25.88 ± 5.28 ya | 42 (5–96) mb | Both |
| Kleinmann 2017 (62) | TNFi (IFX) | Clinical; ∆CS; relapse | 4.7 (0.4–16) yc | 14 | 1:13 | 32 (12–56) yc | 2 ye | Both |
| Novikov 2018 (73) | TNFi (CER) | Clinical; Angio; ∆CS; relapse | 139.4 ± 73.9 ma | 10 | 0:10 | 29.6 ± 6.13 ya | 13.8 ± 9.67 ma | Adults |
| Park 2018 (74) | TNFi (IFX) | Clinical; PET | 4.4 ± 5.2 ya | 11 | 0:11 | 46.8 ± 13.5 ya | 30 we | Adults |
| Banerjee 2020 (79) | TNFi (IFX) | Clinical; PET; ∆CS | NA | 7 | NA | NA | NA | NA |
| Campochiaro 2020 (81) | TNFi (IFX) | Clinical; Angio; PET | 95.5 ± 61.3 ma | 23 | 2:21 | 43.8 ± 14.4 ya | 12 me | NA |
| Mertz 2020 (88) | TNFi (IFX) | Clinical; ∆CS | 3 (1–5) yd | 23 | 4:19 | 33 (23–44) yd | 36.9 (10–58.7) md | NA |
| Erbasan 2020 (98) | TNFi (IFX), Tocilizumab | Clinical; Angio | NA | 15 | NA | NA | 58.3 ± 9.5 ma (IFX), 19.5 ± 5 ma (Tocilizumab) | Both |
| Abisror 2013 (46) | Tocilizumab | Clinical; PET; relapse | NA | 5 | 1:4 | 54 ± 8.69 ya | 13.8 ± 6.91 ma | Adults |
| Goel 2013 (47) | Tocilizumab | Clinical; Angio; inflammatory; ∆CS | 25.5 (1.5–60) mc | 10 | 1:9 | 24.5 (13–53) yc | 5 me | Both |
| Tombetti 2013 (49) | Tocilizumab | Clinical; Angio; inflammatory | 66 (17–82) md | 7 | 0:7 | 24 (23–30) yd | 14 (10–33) md | Adults |
| Canas 2014 (50) | Tocilizumab | Clinical; Angio; inflammatory; ∆CS; relapse | 8.1 ± 10 ya | 8 | 0:8 | 27.8 ± 12.1 ya | 18.5 ± 8.5 ma | Both |
| Loricera 2014 (51) | Tocilizumab | Clinical; Angio; PET; ∆CS | NA | 7 | 0:7 | 34 ± 18.1 ya | 12.3 ± 7.4 ma | Both |
| Novikov 2015 (56) | Tocilizumab | Clinical; Angio; ∆CS; relapse | 48.5 (29–146) mc | 10 | 0:10 | 23.5 (19–56) yc | 6 (3–15) mc | Adults |
| Loricera 2016 (59) | Tocilizumab | Clinical; Angio; PET; ∆CS | 11 (6–50) md | 8 | 0:8 | 34 ± 16 ya | 15.5 (12–24) md | Both |
| Zhou 2017 (68) | Tocilizumab | Clinical; inflammatory; Angio; ∆CS | 34.7 ± 31.6 ma | 13 | 12:1 | 13.2 ± 3.8 ma | 13 (7–20) mc | Adults |
| Mekinian 2018 (70) | Tocilizumab | Clinical; Angio; ∆CS | NA | 46 | 11:35 | 43 (29–54) yc | 0.9 (0.5–2) yc | Adults |
| Kato M 2019 (76) | Tocilizumab | Inflammatory; PET | 176 ± 136 ma | 5 | 1:4 | 42.2 ± 11.6 ya | 6–12 m | NA |
| Shah 2019 (77) | Tocilizumab | Clinical; Angio; ∆CS | 2 (1.1–3.2) yd | 14 | 0:14 | 30.5 (25–40) yd | 6 me | NA |
| Gon 2020 (84) | Tocilizumab | Clinical; ∆CS | NA | 5 | 0:5 | 31.2 ± 3.9 ya | 24–53 mg | NA |
| Kilic 2020 (85) | Tocilizumab | Clinical; Angio; ∆CS | 24 (12–168) mc | 15 | 2:13 | 35 (20–58) yc | 15 (3–42) mc | Adults |
| Mekinian 2020 (87) | Tocilizumab | Clinical; ∆CS; relapse | 8 (0.7–185) mc | 13 | 1:12 | 32 (19–45) yc | 6 me | Adults |
| Prieto–Pena 2020 (91) | Tocilizumab | Clinical; ∆CS | 12 (3–48) mc | 53 | 7:46 | 40.6 ± 14.6 ya | up to 12 m | Adults |
| Wang 2020 (92) | Tocilizumab | Clinical; Angio | NA | 6 | 3:3 | 7 (2–13) yc | 6 me | Children |
| Isobe 2021 (95) | Tocilizumab | Clinical; PET; ∆CS | 14.3 ± 13.9 ya | 19 | 2:17 | 41.4 ± 13.1 ya | 27.6 ± 14.4 ya | NA |
m months, w week, y years, Angio serial angiographic assessment, ∆CS change in corticosteroid dose before and after, ADA adalimumab, AZA azathioprine, CER certolizumab, CsA cyclosporine, CYC cyclophosphamide, ETAN etanercept, GOL golimumab, IFX infliximab, Inflammatory inflammatory markers, LEF leflunomide, MMF mycophenolate mofetil, MTX methotrexate, PET positron emission tomography computerized tomography, TAC tacrolimus, TNFi tumour necrosis factor inhibitors
aMean ± standard deviation
bMean with range
cMedian with range
dMedian with interquartile range
eMean
fMedian
gRange