A. MTX+SASP+ HCQ+IM GCs (n=91) | B. MTX+SASP+ HCQ+oral GCs (n=93) | C. MTX+oral GCs (n=97) | |
---|---|---|---|
Adverse events (AEs) | |||
Serious AE(s)* | 5 (5) | 10 (11) | 10 (10) |
Patients with ≥1 AE(s) | 76 (84) | 82 (88) | 77 (79) |
No. of AEs per patient, median (IQR) IQR) | 2 (1–3) | 2 (1–4) | 2 (1–4) |
Medication changes due to AEs | |||
Switch to MTX SC† | 12 (13) | 21 (23) | 11 (11) |
Lowering MTX dosage <20 mg/wk‡ | 17 (19) | 10 (11) | 22 (23) |
Stop MTX | 11 (12) | 14 (15) | 7 (7) |
Stop SASP | 11 (12) | 8 (9) | NA |
Stop HCQ | 4 (4) | 5 (5) | NA |
Stop biological agents§ | 0 (0) | 2 (2) | 4 (4) |
Observed AEs¶ | |||
Malaise | 20 (22) | 19 (20) | 15 (15) |
Fatigue | 23 (25) | 34 (37) | 40 (41) |
Dizziness | 2 (2) | 10 (11) | 7 (7) |
Headache | 10 (11) | 13 (14) | 13 (13) |
Muscle weakness | 2 (2) | 8 (9) | 7 (7) |
Hypertension | 2 (2) | 4 (4) | 0 (0) |
Palpitations | 0 (0) | 4 (4) | 7 (7) |
Oedema | 3 (3) | 3 (3) | 6 (6) |
Dyspnoea | 0 (0) | 4 (4) | 7 (7) |
Gastrointestinal complaints | 57 (63) | 59 (63) | 41 (42) |
Infection | 12 (13) | 21 (23) | 22 (23) |
Skin problems | 20 (22) | 25 (27) | 27 (28) |
Hair loss | 8 (8) | 7 (8) | 14 (14) |
Hearing loss | 1 (1) | 0 (0) | 0 (0) |
Visual impairment | 7 (8) | 17 (18) | 7 (7) |
Hyperglycaemia | 0 (0) | 1 (1) | 0 (0) |
Feeling ‘sad’ | 7 (8) | 13 (14) | 12 (12) |
Sleep disorder | 4 (4) | 13 (14) | 8 (8) |
Bone marrow depression | 17 (19) | 8 (9) | 7 (7) |
High creatinine | 2 (2) | 6 (6) | 4 (4) |
Elevated liver enzymes | 12 (13) | 15 (16) | 18 (19) |
Results shown are a number (%) unless stated otherwise.
*Serious AEs per treatment are respectively: arm (A) 4× hospitalisation (2× pneumonia, kidney stones and inguinal hernia surgery), 1× lung carcinoma; arm (B) 5× hospitalisation (MTX pneumonitis, severe constipation, transient ischaemic attack, gastroenteritis and observation chest pain), 1× deceased, 1× myocardial infarction and 2× carcinoma (lung and mamma); arm (C) 6× hospitalisation (pneumonia, blood transfusion, syncope, cholecystectomy, inguinal hernia surgery and active rheumatoid arthritis), 1× myocardial infarction, 2× colon carcinoma and 1× maculopathy.
†p=0.039 for B versus C.
‡p=0.028 for B versus C.
§The reasons for stopping biological agents are positive tuberculosis screening (3× in arm C), prostate carcinoma (1× arm B), allergic reaction (1× arm C) and recurrent infections (1× arm B).
¶Bone marrow depression is defined as an anaemia, thrombocytopenia or leucopenia with respectively a haemoglobin level, platelet count and white blood cells count below the lower limit of the normal range. High creatinine, raised liver enzymes and hyperglycaemia are defined as having respectively a creatinine, liver transaminases and glucose level above the upper limit of the normal range.GCs, glucocorticoids; HCQ, hydroxychloroquine; IM, intramuscular; MTX, methotrexate; SASP, sulfasalazine; SC, subcutaneous.