Table 1 Study characteristics
From: Treatment of idiopathic pulmonary fibrosis: a network meta-analysis
Number of randomized patients | ATS/ERS/JRS/ALAT clinical criteria used for diagnosis | Pulmonary function tests/blood gas criteria for enrolment | Intervention (all compared to placebo) | Follow-up used for analysis | Risk of bias | Mortality | Severe adverse events | Industry sponsor | |
|---|---|---|---|---|---|---|---|---|---|
Noth 2012 [21] | Multicenter (22) USA n = 146 | Yes – no bronchoscopy required | Progressive decline in FVC (>10 % in last year) or DLCO (>15 % in last year) | Warfarin | 12 months | High (trial stopped early for harm) | VKA 14/72 Placebo 3/74 | 21/72 12/74 | None |
PANTHER 2012 [22] | Multicenter (25) USA n = 155 | Yes | FVC >50 % predicted DLCO >30 % predicted | Triple therapy (NAC, azathioprine, predinisone) | 12 months | High (trial stopped early for harm) | Triple Rx 8/77 Placebo 1/78 | 24/77 8/78 | None |
Jackson 2010 [23] | Single Center USA n = 29 | Yes – no bronchoscopy required | FVC 40–90 % predicted DLCO 30–90 % predicted | Sildenafil | 6 months | Low | Sildenafil 0/14 Placebo 0/15 | 0/14 0/15 | Pfizer UK |
STEP-IPF 2010 [24] | Multicenter (14) USA n = 180 | Yes | DLCO <35 % predicted | Sildenafil | 6 months | Low | Sildenafil 3/89 Placebo 9/91 | 13/89 15/91 | Pfizer |
Homma 2012 [25] | Multicenter (27) Japan n = 88 | Yes Also required elevated markers pneumocyte injury (KL-6, surfactant protein A & D) | Partial arterial oxygen concentration >70 mmHg at rest | NAC monotherapy | 12 months | Low | NAC 0/44 Placebo 0/46 | Not reported | None |
Tomioka 2005 [26] | Single Center Japan n = 30 | Yes | None | NAC monotherapy | 12 months | Low | NAC 2/15 Placebo 2/15 | 0/15 0/15 | None |
IPF Network 2014 [3] | Multicenter (25) USA n = 264 | Yes | FVC >50 % predicted DLCO >30 % predicted | NAC monotherapy | 12 months | Low | NAC 6/133 Placebo 3/131 | 25/133 20/131 | None |
IFIGENIA 2005 [36] | Multicenter (36) Europe n = 182 | No Histologic or radiologic pattern of UIP with other causes ruled out. Mandatory biopsy in patients <50 years old Mandatory bronchoscopy and duration >3 months | FVC <80 % predicted TLC <90 % predicted DLCO <80 % predicted | NAC monotherapy | 12 months | Low | NAC 7/92 Placebo 8/90 | Not reported | Zambon |
Azuma 2005 [27] | Multicenter (25) Japan n = 108 | Yes | None | Pirfenidone | 9 months | High (trial stopped early for benefit) | Pirfenidone 0/73 Placebo 1/35 | Not reported | Shinogi & Co. |
Taniguchi 2010 [29] | Multicenter (73) Japan n = 212 | Yes | None | Pirfenidone | 12 months | Low | Pirfenidone 3/108 Placebo 4/104 | Not reported | None |
CAPACITY 2011 [28] | Multicenter (110) Worldwide n = 692 | Yes | FVC >50 % predicted DLCO >35 % predicted | Pirfenidone | 24 months | Low | Pirfenidone 27/345 Placebo 34/347 | 113/345 109/347 | Intermune |
King Jr 2014 [4] | Multicenter (127) Worldwide n = 555 | Yes | FVC 50–90 % predicted DLCO 30–90 % predicted FEV1/FVC >80 % | Pirfenidone | 12 months | Low | Pirfenidone 11/278 Placebo 20/277 | 52/278 56/277 | Intermune |
BUILD-1 2008 [30] | Multicenter (29) Europe, N. America n = 158 | Yes | FVC >50 % predicted DLCO >30 % predicted | Bosentan | 12 months | Low | Bosentan 3/74 Placebo 3/84 | 22/74 29/84 | Actelion Pharmaceuticals |
BUILD-3 2011 [31] | Multicenter (119) Worldwide n = 616 | Yes | None | Bosentan | 12 months | Low | Bosentan 17/407 Placebo 7/209 | 129/407 74/209 | Actelion Pharmaceuticals |
MUSIC 2013 [33] | Multicenter (48) Worldwide n = 178 | Yes, with positive biopsy | FVC >50 % predicted DLCO >30 % predicted FEV1/FVC >70 % | Macitentan | 12 months | Low | Macitentan 3/119 Placebo 2/59 | 37/119 20/59 | Actelion Pharmaceuticals |
ARTEMIS 2013 [32] | Mulitcenter (136) Worldwide n = 492 | Yes | None | Ambrisentan | 12 months | High (trial stopped early for harm) | Ambrisentan 26/329 Placebo 6/163 | 73/329 25/163 | Gilead Sciences |
Daniels 2010 [34] | Multicenter (13) USA & Mexico n = 119 | Yes | FVC >55 % predicted DLCO >35 % predicted FEV1/FVC >60 % Progressive decline in FVC (>10 % in last year) | Imatinib | 24 months | Low | Imatinib 8/59 Placebo 10/60 | 18/59 19/60 | Novartis Pharmaceuticals |
Richeldi 2011 [35] | Multicenter (92) Worldwide n = 428 | Yes | FVC >50 % predicted DLCO 30–79 % predicted | Nintedanib | 12 months | Low | Nintedanib 25/343 Placebo 9/85 | 90/343 26/85 | Boehringer Ingelheim |
INPULSUS 2014 [5] | Multicenter (205) Worldwide n = 1061 | Yes | FVC >50 % predicted DLCO 30–79 % predicted | Nintedanib | 12 months | Low | Nintedanib 35/638 Placebo 33/423 | 194/638 127/423 | Boehringer Ingelheim |