Safety results following 26-week treatment, n (%)
| Treatment emergent events* | ADA+2.5 mg MTX (N=98) | ADA+5 mg MTX (N=100) | ADA+10 mg MTX (N=99) | ADA+20 mg MTX (N=98) | Total (N=395) |
|---|---|---|---|---|---|
| Any AE | 61 (62.2) | 59 (59.0) | 66 (66.7) | 68 (69.4) | 254 (64.3) |
| AE leading to discontinuation | 3 (3.1) | 0 | 2 (2.0) | 4 (4.1) | 9 (2.3) |
| Serious AE | 5 (5.1) | 2 (2.0) | 3 (3.0) | 7 (7.1) | 17 (4.3) |
| Severe AE | 3 (3.1) | 2 (2.0) | 5 (5.1) | 6 (6.1) | 16 (4.1) |
| Infectious AE | 20 (20.4) | 17 (17.0) | 24 (24.2) | 34 (34.7) | 95 (24.1) |
| Serious infections | 0 | 2 (2.0) | 0 | 0 | 2 (0.5) |
| Common AEs† | |||||
| Nausea and/or vomiting | 7 (7.1) | 5 (5.0) | 13 (13.1) | 8 (8.2) | 33 (8.4) |
| Stomach pain/discomfort | 6 (6.1) | 6 (6.0) | 7 (7.1) | 12 (12.2) | 31 (7.8) |
| Nasopharyngitis | 3 (3.1) | 6 (6.0) | 6 (6.1) | 11 (11.2) | 26 (6.6) |
| Headache | 4 (4.1) | 6 (6.0) | 5 (5.1) | 9 (9.2) | 24 (6.1) |
| Abnormal hair loss | 1 (1.0) | 5 (5.0) | 6 (6.1) | 8 (8.2) | 20 (5.1) |
| Unexplained diarrhoea | 3 (3.1) | 6 (6.0) | 6 (6.1) | 3 (3.1) | 18 (4.6) |
| Dizziness | 4 (4.1) | 0 | 6 (6.1) | 4 (4.1) | 14 (3.5) |
| Injection site reaction | 1 (1.0) | 5 (5.0) | 5 (5.1) | 3 (3.1) | 14 (3.5) |
| Upper respiratory tract infection | 2 (2.0) | 2 (2.0) | 3 (3.0) | 5 (5.1) | 12 (3.0) |
| Excessive fatigue and/or malaise | 4 (4.1) | 1 (1.0) | 3 (3.0) | 2 (2.0) | 10 (2.5) |
| Skin rash and/or hives | 1 (1.0) | 3 (3.0) | 3 (3.0) | 2 (2.0) | 9 (2.3) |
| Oral ulcers | 0 | 1 (1.0) | 5 (5.1) | 2 (2.0) | 8 (2.0) |
| Fever and/or chills | 0 | 1 (1.0) | 3 (3.0) | 0 | 4 (1.0) |
| Chronic dry cough | 0 | 1 (1.0) | 1 (1.0) | 1 (1.0) | 3 (0.8) |
| Unexplained visual change | 0 | 0 | 2 (2.0) | 1 (1.0) | 3 (0.8) |
| Abnormal sweating | 1 (1.0) | 1 (1.0) | 1 (1.0) | 0 | 3 (0.8) |
| Tinnitus | 1 (1.0) | 0 | 1 (1.0) | 1 (1.0) | 3 (0.8) |
| Conjunctivitis | 0 | 0 | 0 | 2 (2.0) | 2 (0.5) |
| Skin pigment changes | 0 | 0 | 1 (1.0) | 1 (1.0) | 2 (0.5) |
| Unintended weight loss | 1 (1.0) | 1 (1.0) | 0 | 0 | 2 (0.5) |
| Nose bleed | 1 (1.0) | 0 | 0 | 0 | 1 (0.3) |
| Liver function tests‡ | |||||
| ALT, mean change from baseline, IU/L | 2.6 | 2 | 6.6 | 4 | 3.9 |
| ALT >1.5×ULN, n (%) | 4 (4.1) | 4 (4.0) | 5 (5.0) | 7 (7.1) | 20 (5.1) |
| ALT >3.0×ULN, n (%) | 2 (2.0) | 0 | 1 (1.0) | 1 (1.0) | 4 (1.0) |
| AST, mean change from baseline, IU/L | 3.6 | 1.6 | 4.6 | 2.4 | 3 |
| AST >1.5×ULN, n (%) | 4 (4.1) | 2 (2.0) | 3 (3.0) | 4 (4.1) | 13 (3.3) |
| AST >3.0×ULN, n (%) | 2 (2.0) | 0 | 0 | 0 | 2 (0.5) |
| Anaemia | 2 (2.0) | 0 | 1 (1.0) | 2 (2.0) | 5 (1.3) |
| Leucopenia | 1 (1.0) | 1 (1.0) | 0 | 0 | 2 (0.5) |
| Platelet count (× 109/L) | 276.7±73.3 | 264.5±73.3 | 258.9±78.5 | 251.9±73.8 | 262.8±75.0 |
| Platelet count, mean change from baseline (× 109/L,±SD) | −38.5±78.8 | −48.5±70.7 | −40.1±61.8 | −51.0±76.7 | −44.6±72.0 |
*Any treatment emergent event is defined as any AE with an onset date on or after the day of the first ADA dose through 70 days after the last ADA dose.
†Infections, nausea and/or vomiting, stomach pain/discomfort, abnormal hair loss, unexplained diarrhoea, dizziness, excessive fatigue and/or malaise, skin rash and/or hives, oral ulcers, fever and/or chills, chronic dry cough, unexplained visual change, abnormal sweating, tinnitus, conjunctivitis, skin pigment change, unintended weight loss, and nose bleed were prespecified to be assessed at each study visit for relation to MTX, although presented data are irrespective of relation to MTX.
‡N values for liver function tests = 85, 92, 94 and 90 for 2.5, 5, 10 and 20 mg MTX, respectively.
ADA, adalimumab; AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; MTX, methotrexate; ULN, upper limit of normal.