Table 4:
Frequency and Relative Risks Comparing Liver and Other Gastrointestinal Adverse Events for Methotrexate to Placebo During the Randomized Phase of CIRT
| Low dose methotrexate (n=2391) | Placebo (n=2395) | Risk Difference | Hazard ratio (95% CI) | |||||
|---|---|---|---|---|---|---|---|---|
| N (%)* | Rate | 3-year | N (%)* | Rate | 3-year | |||
| Liver test elevation ǂ | 1042 (43.6%) | 36.1 (33.9, 38.3) | 0.56 (0.53, 0.58) | 576 (24.1%) | 15.6 (14.4, 16.9) | 0.32 (0.29, 0.34) | 0.24 (0.20, 0.27) | 2.14 (1.93, 2.37) |
| Mild | 1010 (42.2%) | 34.4 (32.3, 36.5) | 0.54 (0.51, 0.57) | 559 (23.3%) | 15.1 (13.8, 16.3) | 0.31 (0.28, 0.33) | 0.23 (0.20, 0.27) | 2.12 (1.91, 2.35) |
| Moderate | 187 (7.8%) | 4.2 (3.6, 4.9) | 0.12 (0.10, 0.14) | 49 (2.1%) | 1.1 (0.8, 1.4) | 0.03 (0.02, 0.04) | 0.09 (0.07, 0.11) | 3.94 (2.87, 5.39) |
| Severe | 69 (2.9%) | 1.5 (1.2, 1.9) | 0.04 (0.03, 0.06) | 26 (1.1%) | 0.6 (0.4, 0.8) | 0.01 (0.01, 0.02) | 0.03 (0.02, 0.04) | 2.67 (1.70, 4.19) |
| Any liver pathology | 13 (0.5%) | 0.3 (0.1, 0.4) | 0.01 (0.01, 0.02) | 7 (0.3%) | 0.2 (0.0, 0.3) | 0.00 (0.00, 0.01) | 0.01 (0.00, 0.01) | 1.83 (0.73, 4.55) |
| Cirrhosis | 5 (0.2%) | 0.1 (0.0, 0.2) | 0.00 (0.00, 0.01) | 0 (0.0%) | 0.0 (0.0, 0.0) | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.00) | … |
| NASH | 8 (0.3%) | 0.2 (0.1, 0.3) | 0.01 (0.00, 0.02) | 7 (0.3%) | 0.2 (0, 0.3) | 0.00 (0.00, 0.01) | 0.00 (0.00, 0.01) | 1.13 (0.41, 3.08) |
| Gastrointestinal | ||||||||
| Any | 273 (11.4) | 6.4 (5.7, 7.2) | 0.16 (0.14, 0.18) | 224 (9.4) | 5.2 (4.5, 5.9) | 0.13 (0.12, 0.15) | 0.03 (0.00, 0.05) | 1.23 (1.03, 1.47) |
| Mild | 118 (4.9) | 2.6 (2.2, 3.1) | 0.07 (0.06, 0.08) | 101 (4.2) | 2.3 (1.8, 2.7) | 0.06 (0.05, 0.07) | 0.01 (−0.01, 0.02) | 1.17 (0.90, 1.52) |
| Moderate | 132 (5.5) | 3.0 (2.4, 3.5) | 0.08 (0.07, 0.10) | 109 (4.6) | 2.4 (2.0, 2.9) | 0.07 (0.05, 0.08) | 0.01 (0.00, 0.03) | 1.21 (0.94, 1.56) |
| Severe | 53 (2.2) | 1.2 (0.8, 1.5) | 0.03 (0.02, 0.04) | 44 (1.8) | 1.0 (0.7, 1.3) | 0.03 (0.02, 0.04) | 0.00 (−0.01, 0.01) | 1.20 (0.81, 1.79) |
| By sub category | ||||||||
| N/V/D | 174 (7.3) | 3.9 (3.4, 4.5) | 0.10 (0.09, 0.12) | 135 (5.6) | 3.1 (2.5, 3.6) | 0.07 (0.06, 0.09) | 0.03 (0.01, 0.05) | 1.30 (1.03, 1.63) |
| Abdominal pain | 74 (3.1) | 1.6 (1.3, 2.0) | 0.05 (0.04, 0.06) | 60 (2.5) | 1.3 (1.0, 1.7) | 0.04 (0.03, 0.05) | 0.01 (−0.01, 0.02) | 1.23 (0.87, 1.73) |
| GS or cholecystitis | 22 (0.9) | 0.5 (0.3, 0.7) | 0.01 (0.01, 0.02) | 15 (0.6) | 0.3 (0.2, 0.5) | 0.01 (0.00, 0.01) | 0.01 (0.00, 0.01) | 1.45 (0.74, 2.83) |
| Other ** | 42 (1.8) | 0.9 (0.6, 1.2) | 0.02 (0.02, 0.03) | 47 (2.0) | 1.0 (0.7, 1.3) | 0.03 (0.02, 0.04) | 0.00 (−0.02, 0.01) | 0.89 (0.57, 1.38) |
Notes: N/V/D: nausea, vomiting, or diarrhea; GS, gall stones. These numbers are based on the modified intention to treat analyses (see text for details).
N includes first events of a given type and the percentages refer to the number of subjects with a given adverse event divided by all subjects in the respective treatment arm. The first mild, moderate, and severe are all included. As well, the first of each type of adverse event was included. Rates are per 100 person-years. 3-year refers to the cumulative incidence percent risk. Risk difference is based on the 3-year cumulative incidence percent risk.
Other includes to constipation, pancreatitis, small bowel obstruction, weight loss and NOS.