Drugs | Mortality | FVC (% or mL) | 6MWD (m) | AE and He¶ | ADE leading to drug discontinuation |
Nintedanib | −22.3 (−40.3 to 7.2)† | 2.9% (1.5 to 4.1)† | 18 (−12.5 to 48.5)† | −20.8 (−43.8 to 13.1)† | 47.2 (5.2 to 107.1) |
Pirfenidone | −27 (−45.3 to 6.5)*† | 2.5% (−0.1 to 5)† | 25.8 (−2.7 to 53.9)† | −5.3 (−47 to 86.1)† | 75.6 (16.8 to 183.7) |
Sildenafil | −40.3 (−60.5 to 7.2)† | −0.3% (−2.3 to 1.9) | −13.4 (−40.1 to 11.8)† | −53.2 (−73 to 28.5)† | −42.12 (−85.91 to 79.21) |
Pirfenidone +N-acetylcysteine | −21.6 (−46.2 to 31.7)†† | 0.3% (−5.4 to 6)**† | 38.4 (−6.1 to 86.2)**† | 78.4 (−58.4 to 1607.9)**†† | 29.4 (−46.2 to 223.65)**†† |
Pamrevlumab | −43.9 (−64.8 to 32.4)†† | 4.3% (0.5 to 8.1)† | 14.7 (−59.85 to 217.35)† | ||
Pentraxin | 2.7% (1 to 4.8)† | 2 (−19.9 to 31.1) | −30.8 (−63.1 to 80.7)†† | 227.8 (−59.8 to 9691.5)†† | |
Etanercept | 103.7 (−40.3 to 1444.3)†† | 99.6 mL (−139.8 to 340.6)† | −14.7 (−66.6 to 38)† | 87.1 (−50.4 to 685.6)**†† | |
Cyclophosphamide | 4.3 (−66.2 to 656.6)**†† | ||||
Cyclosporine | −5.8 (−67.7 to 790.5)**†† | ||||
Nintedanib+sildenafil | −40.3 (−65.52 to 75.6)**†† | 157.4 mL (−88.3 to 411.1)† | −26.1 (−64.6 to 120)**†† | 14.7 (−54.6 to 181.6) | |
Pirfenidone+sildenafil | −29.488 (−59.7 to 58.2)†† | 118.4 mL (−159.2 to 389.2)**† | 14.2 (−34.3 to 62.5)**† | 3.8 (−56.9 to 217.6)**†† | 75.3 (−39.1 to 604 to.4)**†† |
Corticosteroids | −1.4 (−65.5 to 525.6)**†† | −14% (−23.6 to −4.5)† | |||
Corticosteroids+azathioprine | −34.5 (−69.1 to 306.7)**†† | −9.2% (−20.1 to 1.6)† | −19 (−73.9 to 36)† | ||
Corticosteroids+warfarin | −49.0 (−70.6 to 165.6)**†† | ||||
Imatinib | −7.9 (−51.1 to 126)**†† | −9.9 mL (−245.3 to 227.9)† | 549.8 (−4.6 to 19 090.4)**† | 150.1 (−13.6 to 691.9)**†† | |
Interferon gamma 1-b | −10.1 (−42.5 to 36.7)**†† | −40 mL (−265.2 to 186.8)**† | −7.8 (−44.5 to 29)**† | 11.5 (−37.7 to 121.5)† | 107.1 (12.6 to 323.4)† |
N-acetylcysteine | 37.4 (−22.3 to 181.4)†† | 0.02% (−2.3 to 2.3)† | 49.7 (16.6 to 81.3)**† | −4.6 (−50.7 to 102.2)†† | −18.9 (−7.4 to 109.2)** |
Simtuzumab | −4.3 (−44.6 to 86.4)†† | −6.4% (−8.9 to −3.9) | −39.9 (−73.8 to −6.1)† | −5.4 (−30.3 to 31.6)†† | −9.4 (−58.8 to 91.3) |
ERA | −9.4 (−32.4 to 30.2)†† | −0.8% (−5.3 to 3.6)† | 9.3 (−17.6 to 37.9)† | 27.7 (−27 to 124.6)† | 15.7 (−21 to 90.3) |
Colchicine | 141.1 (−13.7 to 784.1)†† | −12.1% (−19.6 to −4.8)† | −18.4 (−65.4 to 191.5)**†† | ||
Triple therapy‡‡ | 270.7 (−3.6 to 3528)† | −9.9 mL (−236.9 to 216.8)† | −19 (−73.9 to 36)† | 208.2 (9.5 to 1023)† | |
Warfarin | 205.2 (7.2 to 1130.4)**† | −0.9 mL (−3.8 to 1.9)† | 11.4 (−47 to 71)**† | 80.08 (1.54 to 231)**† | |
I2 | 5% | 6% and 7% | 0% | 19% | 2% |
Benefit | Harm | No effect |
High | High | High |
Moderate | Moderate | Moderate |
Low | Low | Low |
Very low | Very low | Very low |
Colour arrangement reflects certainty of evidence. All estimates are network estimates, unless indicated (direct estimate), based on higher certainty of evidence.
Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group grades of evidence
Interpretation: Each node estimate is compared against placebo. Most estimates unless otherwise specified are the network estimates. The comparative effectiveness of each drug versus another can be done by simply comparing how well each drug compares against placebo. If the network estimate is not presented due to lower certainty of the evidence, then direct comparisons need to be made using the network estimates provided in online supplemental appendix 3. More detail on rating the certainty of the evidence is found in online supplemental appendix 2.
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
Ratings.
*Direct estimate.
†Imprecision ((once)
‡We analysed two networks for FVC, one with trials reporting mL and one reporting percent change predicted. We reported the highest rated evidence for each when there was overlap in nodes.
§Corticosteroids+Azathioprine+N-acetylcysteine.
¶AE and H=acute exacerbations and hospitalizations.
**Risk of bias.
†† Imprecision (twice)
‡‡Triple therapy (corticosteroids+azathioprine+N-acetylcysteine)
FVC, forced vital capacity; 6MWD, 6-min walk distance.