Table 5:
Frequency and Relative Risks Comparing Infection and Pulmonary 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 | |||
| Any infection | 531 (22.2) | 13.6 (12.4, 14.8) | 0.31 (0.28, 0.34) | 466 (19.5) | 11.8 (10.8, 12.9) | 0.27 (0.25, 0.30) | 0.04 (0.00, 0.07) | 1.15 (1.01, 1.30) |
| Mild | 340 (14.2) | 8.2 (7.4, 9.1) | 0.20 (0.18, 0.23) | 282 (11.8) | 6.8 (6.0, 7.6) | 0.16 (0.14, 0.18) | 0.04 (0.01, 0.07) | 1.21 (1.03, 1.42) |
| Moderate | 241 (10.1) | 5.6 (4.9, 6.3) | 0.14 (0.12, 0.16) | 219 (9.1) | 5.1 (4.4, 5.7) | 0.13 (0.12, 0.16) | 0.01 (−0.02, 0.03) | 1.10 (0.91, 1.32) |
| Severe | 51 (2.1) | 1.1 (0.8, 1.4) | 0.03 (0.02, 0.04) | 50 (2.1) | 1.1 (0.8, 1.4) | 0.03 (0.03, 0.05) | 0.00 (−0.02, 0.01) | 1.02 (0.69, 1.50) |
| Type of infection | ||||||||
| URI/flu syndrome | 125 (5.2) | 2.8 (2.3, 3.3) | 0.08 (0.07, 0.10) | 105 (4.4) | 2.4 (1.9, 2.8) | 0.06 (0.05, 0.08) | 0.01 (0.00, 0.03) | 1.19 (0.92, 1.54) |
| Skin and soft tissue | 129 (5.4) | 2.9 (2.4, 3.4) | 0.08 (0.07, 0.09) | 125 (5.2) | 2.8 (2.3, 3.3) | 0.08 (0.07, 0.10) | 0.00 (−0.02, 0.02) | 1.03 (0.80, 1.31) |
| Pneumonia | 67 (2.8) | 1.5 (1.1, 1.8) | 0.04 (0.03, 0.06) | 52 (2.2) | 1.1 (0.8, 1.4) | 0.03 (0.02, 0.04) | 0.01 (0.00, 0.02) | 1.28 (0.89, 1.83) |
| EENT and dental | 182 (7.6) | 4.1 (3.5, 4.7) | 0.11 (0.09, 0.13) | 149 (6.2) | 3.4 (2.9, 4.0) | 0.08 (0.07, 0.10) | 0.03 (0.01, 0.05) | 1.21 (0.98, 1.51) |
| Genitourinary | 111 (4.6) | 2.5 (2.0, 2.9) | 0.06 (0.05, 0.08) | 86 (3.6) | 1.9 (1.5, 2.3) | 0.05 (0.04, 0.07) | 0.01 (−0.01, 0.03) | 1.30 (0.98, 1.72) |
| Gastrointestinal | 37 (1.6) | 0.8 (0.5, 1.1) | 0.02 (0.02, 0.03) | 35 (1.5) | 0.8 (0.5, 1.0) | 0.02 (0.02, 0.03) | 0.00 (−0.01, 0.01) | 1.05 (0.66, 1.67) |
| Shingles | 23 (1.0) | 0.5 (0.3, 0.7) | 0.01 (0.01, 0.02) | 17 (0.7) | 0.4 (0.2, 0.5) | 0.01 (0.01, 0.02) | 0.00 (0.00, 0.01) | 1.34 (0.72, 2.51) |
| Bone and Joint | 21 (0.9) | 0.5 (0.3, 0.6) | 0.01 (0.01, 0.02) | 11 (0.5) | 0.2 (0.1, 0.4) | 0.01 (0.01, 0.02) | 0.00 (0.00, 0.01) | 1.91 (0.92, 3.96) |
| Yeast | 6 (0.3) | 0.1 (0.0, 0.2) | 0.00 (0.00, 0.01) | 9 (0.4) | 0.2 (0.1, 0.3) | 0.01 (0.00, 0.01) | 0.00 (0.00, 0.00) | 0.66 (0.24, 1.83) |
| Sepsis | 12 (0.5) | 0.3 (0.1, 0.4) | 0.01 (0.00, 0.01) | 14 (0.6) | 0.3 (0.1, 0.5) | 0.01 (0.00, 0.01) | 0.00 (−0.01, 0.00) | 0.85 (0.39, 1.82) |
| NOS | 22 (0.9) | 0.5 (0.3, 0.7) | 0.01 (0.01, 0.03) | 22 (0.9) | 0.5 (0.3, 0.7) | 0.01 (0.01, 0.02) | 0.00 (−0.01, 0.01) | 0.99 (0.55, 1.79) |
| Pulmonary events | 137 (5.7) | 3.1 (2.6, 3.6) | 0.08 (0.07, 0.10) | 135 (5.6) | 3.1 (2.5, 3.6) | 0.06 (0.05, 0.07) | 0.03 (0.01, 0.04) | 1.42 (1.14, 1.77) |
| Mild | 77 (3.2) | 1.7 (1.3, 2.1) | 0.05 (0.04, 0.06) | 66 (2.8) | 1.5 (1.1, 1.8) | 0.03 (0.02, 0.05) | 0.01 (0.00, 0.03) | 1.40 (1.02, 1.93) |
| Moderate | 50 (2.1) | 1.1 (0.8, 1.4) | 0.03 (0.02, 0.04) | 61 (2.6) | 1.3 (1.0, 1.7) | 0.02 (0.01, 0.03) | 0.01 (0.00, 0.02) | 1.41 (1.02, 1.96) |
| Severe | 13 (0.5) | 0.3 (0.1, 0.4) | 0.01 (0.00, 0.02) | 8 (0.3) | 0.2 (0.1, 0.3) | 0.00 (0.00, 0.00) | 0.01 (0.00, 0.01) | 2.99 (1.34, 6.65) |
| Type of pulmonary event | ||||||||
| Bronchitis | 116 (4.9) | 2.6 (2.1, 3.1) | 0.07 (0.06, 0.08) | 73 (3.1) | 1.6 (1.3, 2.0) | 0.04 (0.03, 0.06) | 0.02 (0.01, 0.04) | 1.60 (1.19, 2.14) |
| Cough | 4 (0.2) | 0.1 (0.0, 0.2) | 0.00 (0.00, 0.01) | 5 (0.2) | 0.1 (0.0, 0.2) | 0.00 (0.00, 0.01) | 0.00 (0.00, 0.00) | 0.80 (0.21, 2.96) |
| Short of breath | 11 (0.5) | 0.2 (0.1, 0.4) | 0.04 (0.03, 0.06) | 8 (0.3) | 0.2 (0.1, 0.3) | 0.03 (0.02, 0.04) | 0.01 (0.00, 0.02) | 1.36 (0.55, 3.38) |
| COPD/asthma flare | 3 (0.1) | 0.1 (0.0, 0.1) | 0.01 (0.00, 0.01) | 6 (0.3) | 0.1 (0.0, 0.2) | 0.01 (0.00, 0.02) | 0.00 (−0.01, 0.00) | 0.50 (0.13, 1.99) |
| Pneumonitis | 7 (0.3) | 0.2 (0.0, 0.3) | 0.00 (0.00, 0.01) | 1 (0.04) | 0.0 (0.0, 0.1) | 0.00 (0.00, 0.01) | 0.00 (0.00, 0.00) | 6.94 (0.85, 56.0) |
| NOS | 1 (0.0) | 0 (0.0, 0.1) | 0.00 (0.00, 0.01) | 2 (0.1) | 0.0 (0.0, 0.1) | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.01) | 0.48 (0.04, 5.37) |
Notes: 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. CI, confidence interval; HR, hazard ratio; EENT, eye, ear, nose, throat, and dental; COPD, chronic obstructive pulmonary disease; NOS, not otherwise specified; URI, upper respiratory infection.