Adverse events in 60 patients with JIA in three treatment arms: TNF, COMBO or MTX
| TNF | COMBO | MTX | All | ||
|---|---|---|---|---|---|
| n (Patient-years) | 20 (20.8) | 20 (19.5) | 20 (17.0) | 60 (57.3) | |
| All adverse events, n (events/patient-year) | 100 (4.8) | 106 (5.4) | 111 (6.5) | 317 | (5.5) |
| Common adverse events (≥20% of patients) | no. of events (events/patient-year) no. of patients | All events | All n (%)* | ||
| All infections | 36 (1.7) 16 | 35 (1.8) 18 | 48 (2.8) 17 | 120 | 51 (85) |
| Upper respiratory tract infection | 25 (1.2) 15 | 24 (1.2) 18 | 28 (1.6) 17 | 77 | 50 (83) |
| Gastroenteritis | 3 (0.1) 3 | 8 (0.4) 6 | 6 (0.4) 6 | 17 | 15 (25) |
| Methotrexate-related nausea | 6 (0.3) 5 | 7 (0.4) 7 | 7 (0.4) 7 | 20 | 19 (32) |
| Accidental injuries (mainly due to sports) | 6 (0.3) 5 | 4 (0.2) 4 | 6 (0.4) 5 | 16 | 14 (24) |
| Unspecified nausea and/or loss of appetite | 0 | 13 (0.7) 8 | 4 (0.2) 4 | 17 | 12 (20) |
| Other adverse events | |||||
| Infections requiring oral antimicrobials | 6 (0.3) 2 | 2 (0.1) 2 | 9 (0.5) 6 | 17 | 10 (17) |
| Mild elevation of ALT (1.2–2.0×ULN) | 7 (0.3) 7 | 2 (0.1) 2 | 2 (0.1) 2 | 11 | 11 (19) |
| Leucopaenia (2.0–3.5×109/l) | 2 (0.1) 2 | 6 (0.3) 5 | 2 (0.1) 2 | 10 | 9 (15) |
| Abdominal pain | 3 (0.1) 2 | 2 (0.1) 2 | 4 (0.2) 4 | 9 | 8 (14) |
| Moderate elevation of ALT (2.0–3.0×ULN) | 2 (0.1) 2 | 1 (<0.1) 1 | 3 (0.2) 3 | 6 | 6 (10) |
| Mild neutropaenia (1.0–1.5×109/l) | 2 (0.1) 1 | 3 (0.2) 2 | 1 (<0.1) 1 | 6 | 4 (7) |
| Nightmares† | 0 | 4 (0.2) 4 | 0 | 4 | 4 (7) |
| Herpes simplex infection | 0 | 0 | 4 (0.2) 2 | 4 | 2 (3) |
| Moderate neutropaenia (0.5–1.0×109/l) | 1 (<0.1) 1 | 1 (<0.1) 1 | 0 | 2 | 2 (3) |
| High-energy fractures | 1 (<0.1) 1 | 0 | 1 (<0.1) 1 | 2 | 2 (3) |
| Transient infusion-related reaction | 2 (0.1) 2 | 0 | 0 | 2 | 2 (3) |
| Newly positive antinuclear antibodies | 1 (<0.1) 1 | 0 | 0 | 1 | 1 (2) |
| Adverse events of special interest‡ | 1 (<0.1) 1 | 2 (0.1) 2 | 18 (1.1) 12 | ||
| Transient elevation of ALT (>3.0×ULN)§ | 0 | 0 | 6 (0.4) 5 | 6 | 5 (8) |
| Infections requiring hospitalisation¶ | 0 | 0 | 3 (0.2) 3 | 3 | 3 (5) |
| Temporary asymptomatic corticosteroid-induced adrenal insufficiency** | 1 (<0.1) 1 | 0 | 2 (0.1) 2 | 3 | 3 (5) |
| Synovitis of cervical spine†† | 0 | 0 | 3 (0.2) 3 | 3 | 3 (5) |
| Bone erosion†† | 0 | 1 (<0.1) 1 | 1 (<0.1) 1 | 2 | 2 (3) |
| First episode of chronic anterior uveitis | 0 | 0 | 2 (0.1) 2 | 2 | 2 (3) |
| Severe nausea and weight loss† | 0 | 1 (<0.1) 1 | 1 (<0.1) 1 | 2 | 2 (3) |
Within each treatment arm are shown the number of events, events per patient-year, and the number of patients with each event. The last two columns show cumulative frequencies.
↵* Cumulative number of patients with adverse events. In parenthesis is shown the proportion (%) of those patients from all 59 patients.
↵† One patient discontinued hydroxychloroquine due to nightmares and another sulphasalazine due to abdominal pain and weight loss.
↵‡ Possibly related to treatment. Serious adverse events were defined as death or events that were life threatening, required hospitalisation or prolonged medical intervention. Three events (hospitalisations) were considered serious.
↵§ Methotrexate dose 13, 14, 17, 19 and 25 mg/m2 subcutaneously. After pause, all except one (changing 25 to 17 mg/m2) continued at previous dosage. Only one episode occurred with concurrent infection (gastroenteritis).
↵¶ Gastroenteritis, viral pneumonia, herpes simplex in mouth and pharynx.
↵** Detected by routine adrenocorticotropic hormone stimulation test.
↵†† Identified with gadolinium-enhanced MRI.
ALT, alanine aminotransferase; COMBO, sulphasalazine and hydroxychloroquine; JIA, juvenile idiopathic arthritis; MTX, methotrexate alone; TNF, infliximab and methotrexate; ULN, upper limit of the normal range.