Intestinal perforations in patients on bDMARDs (IL-6 inhibitors) (randomised controlled trials)
| Study ID (trial) | Follow-up | Intervention | N | N intestinal perforations (%) | Risk of bias |
| Placebo-controlled trials | |||||
| Aletaha 2017 Lancet (SIRROUND-T)73 | 24 | PBO | 294 | 0 (0.0) | Low |
| SIR 50 Q4W | 292 | 2 (0.7) | |||
| SIR 100 Q2W | 292 | 3 (1.0)* | |||
| Fleischmann 2017 Arthritis Rheumatol (TARGET)79 | 24 | PBO | 181 | 0 (0.0) | Low |
| SAR 150 Q2W | 181 | 0 (0.0) | |||
| SAR 200 Q2W | 184 | 0 (0.0) | |||
| Takeuchi 2016 Mod Rheumatol85 | 12 | PBO | 29 | 0 (0.0) | Unclear |
| OKZ 60 Q4W | 32 | 0 (0.0) | |||
| OKZ 120 Q4W | 32 | 0 (0.0) | |||
| OKZ 240 Q4W | 26 | 0 (0.0) | |||
| Takeuchi 2017 Ann Rheum Dis (SIRROUND-D)86 | 52 | PBO | 556 | 1 (0.2)† | Unclear |
| SIR 50 Q4W | 663 | 1 (0.2)‡ | |||
| SIR 100 Q2W | 662 | 0 (0.0) | |||
| Head-to-head trials | |||||
| Burmester 2017 Ann Rheum Dis (MONARCH)74 | 24 | ADA 40 Q2W | 184 | 0 (0.0) | Low |
| SAR 200 Q2W | 184 | 0 (0.0) | |||
| Taylor 2018 Ann Rheum Dis (SIRROUND-H)88 | 68 | ADA 40 Q2W | 186 | 0 (0.0) | Low |
| SIR 50 Q4W | 186 | 1 (0.5)§ | |||
| SIR 100 Q2W | 187 | 1 (0.5)§ | |||
*Two additional perforations occurred in patients switching from placebo to SIR 100 after week 24 up to week 52; thus, in total, seven perforations occurred (three upper gastrointestinal perforations and four lower intestinal perforations).
†Upper gastrointestinal perforation.
‡Lower intestinal perforation (patients randomised to PBO with early escape to SIR 50).
§Location not specified.
ADA, adalimumab; OKZ, olokizumab; PBO, placebo; Q2W, every 2 weeks; Q4W, every 4 weeks; SAR, sarilumab; SIR, sirukumab.