Efficacy outcomes and biomarkers analyses
| (A) Induction study, week 8 (FAS) | |||
|---|---|---|---|
| Placebo N=90 | Tofacitinib 5 mg twice daily N=85 | Tofacitinib 10 mg twice daily N=86 | |
| Clinical remission (NRI) | |||
| n (%)† | 33 (36.7) | 37 (43.5) | 37 (43.0) |
| Remission in TNFi-experienced patients (NRI) | |||
| n/N (%)† | 25/69 (36.2) | 26/68 (38.2) | 28/66 (42.4) |
| Clinical response-100 or remission (NRI) | |||
| n (%)† | 50 (55.6) | 61 (71.8)* | 60 (69.8) |
| Clinical response-100 or remission in TNFi-experienced patients (NRI) | |||
| n/N (%)† | 38/69 (55.1) | 46/68 (67.7) | 48/66 (72.7) |
| Clinical response-100 (NRI) | |||
| n (%)† | 49 (54.4) | 60 (70.6)* | 59 (68.6) |
| Clinical response-70 (NRI) | |||
| n (%)† | 56 (62.2) | 65 (76.5)* | 64 (74.4) |
| PRO2-75 (NRI) | |||
| n (%)‡ | 36 (40.0) | 50 (58.8)* | 48 (55.8)* |
| PRO3-80 (NRI) | |||
| n (%)§ | 22 (24.4) | 33 (38.8)* | 31 (36.1) |
| CDAI score | |||
| Adjusted estimate, change from baseline (SE)¶ | −117.4 (10.3) | −149.7 (10.7)* | −157.3 (10.7)* |
| CRP levels (mg/L) | |||
| Observed median (min–max) | 5.9 (0.4–132.5) | 3.2 (0.1–69.0) | 2.4 (0.1–65.3) |
| Adjusted estimate, change from baseline in log-transformed value (SE)¶ | 0.12 (0.12) | −0.42 (0.12)** | −0.73 (0.12)*** |
| FCP levels (mg/kg) | |||
| Observed median (min–max) | 266.0 (25.2–3578.0) | 310.0 (25.2–1104.0) | 302.5 (25.2–1251.0) |
| Adjusted estimate, change from baseline in log-transformed value (SE)¶ | −0.02 (0.12) | −0.31 (0.14) | −0.30 (0.13) |
| (B) Maintenance study, week 26 (mFAS) | |||
|
Placebo N=42 | Tofacitinib 5 mg twice daily N=43 | Tofacitinib 10 mg twice daily N=43 | |
| Clinical response-100 or remission (NRI) | |||
| n (%)† | 16 (38.1) | 17 (39.5) | 24 (55.8) |
| Clinical remission (NRI) | |||
| n (%)† | 12 (28.6) | 16 (37.2) | 18 (41.9) |
| Clinical response-100 or remission in TNFi-experienced patients (NRI) | |||
| n/N (%)† | 11/27 (40.7) | 13/35 (37.1) | 17/35 (48.6) |
| Clinical remission in TNFi-experienced patients (NRI) | |||
| n/N (%)† | 8/27 (29.6) | 12/35 (34.3) | 12/35 (34.3) |
| Sustained remission at both week 20 and 26 (NRI) | |||
| n (%)† | 9 (21.4) | 10 (23.3) | 17 (39.5) |
| Clinical response-100 (NRI) | |||
| n (%)† | 15 (35.7) | 16 (37.2) | 24 (55.8) |
| CDAI score | |||
| Adjusted estimate, change from baseline (SE)¶ | 69.5 (22.1) | 63.5 (21.6) | 19.1 (21.1) |
| CRP levels at week 26 (mg/L) | |||
| Observed median (min–max) | 9.8 (1.5–148.7) | 9.4 (0.3–46.1) | 2.5 (0.1–14.7) |
| Adjusted estimate, change from baseline in log-transformed value (SE)¶ | 1.73 (0.26) | 1.12 (0.25) | 0.11 (0.23)*** |
| FCP levels at week 26 (mg/kg) | |||
| Observed median (min–max) | 689.5 (60.0–4100.0) | 445.5 (59.0–999.0) | 177.5 (25.2–707.0) |
| Adjusted estimate, change from baseline in log-transformed value (SE)¶ | 1.13 (0.21) | 0.57 (0.19)* | −0.07 (0.18)*** |
†Statistical significance (p<0.05) based on the Cochran-Mantel-Haenszel test statistic stratified on prior use of TNFi treatments.
‡Clinical remission based on the sum of the first two components with multipliers (stool frequency score+abdominal pain score) <75.
§Clinical remission based on the sum of the first three components with multipliers (stool frequency score+abdominal pain score+general well-being score) <80.
¶Statistical significance based on a linear mixed-effects model for change in CDAI score, change in log-transformed CRP and FCP.
*p<0.05; **p<0.001; ***p<0.0001, vs placebo.
CDAI, Crohn's disease activity index; CRP, C-reactive protein; FAS, full analysis set; FCP, faecal calprotectin; mFAS, modified FAS (excluding placebo responders of the induction study); NRI, non-responder imputation; PRO, patient-reported outcomes; TNFi, tumour necrosis factor inhibitors.