IRs (patients with first events/100 PY; 95% CI) and HRs (95% CIs) for malignancies excluding NMSC and subtypes of interest (total time), and NMSC and subtypes of interest (28-day on-treatment time) in ORAL Surveillance
| Combined tofacitinib doses* (N=2911) | Tofacitinib 5 mg two times per day (N=1455) | Tofacitinib 10 mg two times per day (N=1456) | TNFi (N=1451) | |
| Malignancies excluding NMSC, n (%) | 122 (4.19) | 62 (4.26) | 60 (4.12) | 42 (2.89) |
| IR (95% CI) (PY) | 1.13 (0.94 to 1.35) (10 803) | 1.13 (0.87 to 1.45) (5491) | 1.13 (0.86 to 1.45) (5312) | 0.77 (0.55 to 1.04) (5482) |
| HR (95% CI) for tofacitinib vs TNFi | 1.48 (1.04 to 2.09) | 1.47 (1.00 to 2.18) | 1.48 (1.00 to 2.19) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 1.00 (0.70 to 1.43) | – |
| NNH vs TNFi, PY (95% CI)† | 275 (149 to 1759) | 276 (−∞ to −76 653 and 138 to ∞) | 275 (−∞ to −22 457 and 137 to ∞) | Referent |
| NNH vs TNFi, patients exposed for 5 years‡ | 55 | 55 | 55 | Referent |
| Breast cancer,§ n (%) (N) | 17 (0.74) (2293) | 10 (0.86) (1169) | 7 (0.62) (1124) | 10 (0.90) (1117) |
| IR (95% CI) (PY) | 0.20 (0.11 to 0.31) (8645) | 0.22 (0.11 to 0.41) (4473) | 0.17 (0.07 to 0.35) (4173) | 0.24 (0.11 to 0.43) (4249) |
| HR (95% CI) for tofacitinib vs TNFi | 0.83 (0.38 to 1.82) | 0.95 (0.39 to 2.28) | 0.71 (0.27 to 1.87) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 0.75 (0.29 to 1.97) | – |
| Lymphoma, n (%) | 10 (0.34) | 4 (0.27) | 6 (0.41) | 1 (0.07) |
| IR (95% CI) (PY) | 0.09 (0.04 to 0.17) (10 913) | 0.07 (0.02 to 0.18) (5548) | 0.11 (0.04 to 0.24) (5364) | 0.02 (0.00 to 0.10) (5526) |
| HR (95% CI) for tofacitinib vs TNFi | 5.09 (0.65 to 39.78) | 3.99 (0.45 to 35.70) | 6.24 (0.75 to 51.86) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 1.56 (0.44 to 5.54) | – |
| Lung cancer, n (%) | 30 (1.03) | 13 (0.89) | 17 (1.17) | 7 (0.48) |
| IR (95% CI) (PY) | 0.28 (0.19 to 0.39) (10 901) | 0.23 (0.12 to 0.40) (5542) | 0.32 (0.18 to 0.51) (5359) | 0.13 (0.05 to 0.26) (5517) |
| HR (95% CI) for tofacitinib vs TNFi | 2.17 (0.95 to 4.93) | 1.84 (0.74 to 4.62) | 2.50 (1.04 to 6.02) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 1.35 (0.66 to 2.79) | – |
| NNH vs TNFi, PY (95% CI)† | 674 (352 to 8205) | 929 (-∞ to −1972 and 376 to ∞) | 525 (272 to 7906) | Referent |
| NNH vs TNFi, patients exposed for 5 years‡ | 135 | 186 | 105 | Referent |
| Non-small cell lung cancer,¶ n (%) | 24 (0.82) | 8 (0.55) | 16 (1.10) | 7 (0.48) |
| IR (95% CI) (PY) | 0.22 (0.14 to 0.33) (10 904) | 0.14 (0.06 to 0.28) (5545) | 0.30 (0.17 to 0.48) (5359) | 0.13 (0.05 to 0.26) (5517) |
| HR (95% CI) for tofacitinib vs TNFi | 1.73 (0.74 to 4.01) | 1.13 (0.41 to 3.13) | 2.34 (0.96 to 5.70) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 2.07 (0.88 to 4.83) | – |
| Small cell lung cancer,¶ n (%) | 5 (0.17) | 4 (0.27) | 1 (0.07) | 0 |
| IR (95% CI) (PY) | 0.05 (0.01 to 0.11) (10 919) | 0.07 (0.02 to 0.18) (5548) | 0.02 (0.00 to 0.10) (5371) | 0.00 (0.00 to 0.07) (5526) |
| HR (95% CI) for tofacitinib vs TNFi | NI | NI | NI | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 0.26 (0.03 to 2.33) | – |
| Melanoma, n (%) | 2 (0.07) | 1 (0.07) | 1 (0.07) | 5 (0.34) |
| IR (95% CI) (PY) | 0.02 (0.00 to 0.07) (10 919) | 0.02 (0.00 to 0.10) (5548) | 0.02 (0.00 to 0.10) (5371) | 0.09 (0.03 to 0.21) (5517) |
| HR (95% CI) for tofacitinib vs TNFi | 0.20 (0.04 to 1.04) | 0.20 (0.02 to 1.71) | 0.20 (0.02 to 1.75) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | NI | – |
| Prostate cancer,** n (%) (N) | 9 (1.46) (618) | 1 (0.35) (286) | 8 (2.41) (332) | 3 (0.90) (334) |
| IR (95% CI) (PY) | 0.40 (0.18 to 0.76) (2245) | 0.09 (0.00 to 0.52) (1070) | 0.68 (0.29 to 1.34) (1175) | 0.24 (0.05 to 0.69) (1262) |
| HR (95% CI) for tofacitinib vs TNFi | 1.69 (0.46 to 6.24) | 0.39 (0.04 to 3.79) | 2.87 (0.76 to 10.82) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 7.27 (0.91 to 58.11) | – |
| Colorectal cancer, n (%) | 8 (0.27) | 4 (0.27) | 4 (0.27) | 4 (0.28) |
| IR (95% CI) (PY) | 0.07 (0.03 to 0.14) (10 918) | 0.07 (0.02 to 0.18) (5550) | 0.07 (0.02 to 0.19) (5368) | 0.07 (0.02 to 0.19) (5525) |
| HR (95% CI) for tofacitinib vs TNFi | 1.01 (0.30 to 3.34) | 0.99 (0.25 to 3.97) | 1.02 (0.25 to 4.08) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 1.03 (0.26 to 4.10) | – |
| Pancreatic cancer, n (%) | 4 (0.14) | 3 (0.21) | 1 (0.07) | 1 (0.07) |
| IR (95% CI) (PY) | 0.04 (0.01 to 0.09) (10 920) | 0.05 (0.01 to 0.16) (5549) | 0.02 (0.00 to 0.10) (5372) | 0.02 (0.00 to 0.10) (5526) |
| HR (95% CI) for tofacitinib vs TNFi | 2.04 (0.23 to 18.24) | 3.00 (0.31 to 28.87) | 1.04 (0.06 to 16.61) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | NI | – |
| NMSC, n (%) | 64 (2.20) | 31 (2.13) | 33 (2.27) | 16 (1.10) |
| IR (95% CI) (PY) | 0.64 (0.50 to 0.82) (9927) | 0.61 (0.41 to 0.86) (5116) | 0.69 (0.47 to 0.96) (4812) | 0.32 (0.18 to 0.52) (5020) |
| HR (95% CI) for tofacitinib vs TNFi | 2.02 (1.17 to 3.50) | 1.90 (1.04 to 3.47) | 2.16 (1.19 to 3.92) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 1.14 (0.70 to 1.86) | – |
| NNH vs TNFi, PY (95% CI)† | 307 (182 to 963) | 348 (181 to 4374) | 272 (154 to 1166) | Referent |
| NNH vs TNFi, patients exposed for 5 years‡ | 61 | 70 | 54 | Referent |
| Basal cell carcinoma, n (%) | 35 (1.20) | 19 (1.31) | 16 (1.10) | 13 (0.90) |
| IR (95% CI) (PY) | 0.35 (0.24 to 0.49) (9967) | 0.37 (0.22 to 0.58) (5133) | 0.33 (0.19 to 0.54) (4834) | 0.26 (0.14 to 0.44) (5027) |
| HR (95% CI) for tofacitinib vs TNFi | 1.36 (0.72 to 2.56) | 1.43 (0.71 to 2.90) | 1.28 (0.61 to 2.66) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 0.89 (0.46 to 1.74) | – |
| Cutaneous squamous cell carcinoma, n (%) | 37 (1.27) | 15 (1.03) | 22 (1.51) | 8 (0.55) |
| IR (95% CI) (PY) | 0.37 (0.26 to 0.51) (9987) | 0.29 (0.16 to 0.48) (5150) | 0.45 (0.29 to 0.69) (4837) | 0.16 (0.07 to 0.31) (5030) |
| HR (95% CI) for tofacitinib vs TNFi | 2.32 (1.08 to 4.99) | 1.82 (0.77 to 4.30) | 2.86 (1.27 to 6.43) | Referent |
| HR (95% CI) for tofacitinib 10 vs 5 mg two times per day | – | Referent | 1.57 (0.82 to 3.03) | – |
For patients randomised to the tofacitinib 10 mg two times per day group who had their dose of tofacitinib reduced to 5 mg two times per day, the data collected after patients were switched to tofacitinib 5 mg two times per day were counted in the tofacitinib 10 mg two times per day group.
For malignancies excluding NMSC and its subtypes of interest, the risk period was total time, defined as time from first dose of trial drug until last contact date.
For NMSC and its subtypes of interest, the risk period was the 28-day on-treatment time, defined as time from first until last dose of trial drug + 28 days, or to last contact date, whichever was earlier.
IRs, HRs and NNHs for malignancies excluding NMSC, and IRs and HRs for NMSC have been presented previously.12
*Includes patients who received tofacitinib 5 or 10 mg two times per day in ORAL Surveillance.
†Positive NNH refers to the number of PY of tofacitinib exposure needed to have one additional patient with an event compared with TNFi. Negative NNH refers to the reverse.
‡Number of patients who would need to be treated with tofacitinib for 5 years to have one additional event compared with TNFi.
§Female only.
¶One patient in the tofacitinib 5 mg two times per day group with lung cancer did not have sufficient information to classify as having small or non-small cell lung cancer.
**Male only.
IR, incidence rate; n, number of patients with events; N, number of evaluable patients; NI, non-informative (HRs (95% CI) were not informative when the total number of patients with events was ≤2 for the corresponding pair of treatments in the comparison, or when one of the treatments in the comparison had 0 events); NMSC, non-melanoma skin cancer; NNH, number needed to harm; PY, patient-years; TNFi, tumour necrosis factor inhibitors.