Table 3

Number (%) of patients with (serious) adverse events and treatment alterations due to side effects for each induction therapy group

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 MTX11 (12)14 (15)7 (7)
 Stop SASP11 (12)8 (9)NA
 Stop HCQ4 (4)5 (5)NA
 Stop biological agents§0 (0)2 (2)4 (4)
Observed AEs¶
 Malaise20 (22)19 (20)15 (15)
 Fatigue23 (25)34 (37)40 (41)
 Dizziness2 (2)10 (11)7 (7)
 Headache10 (11)13 (14)13 (13)
 Muscle weakness2 (2)8 (9)7 (7)
 Hypertension2 (2)4 (4)0 (0)
 Palpitations0 (0)4 (4)7 (7)
 Oedema3 (3)3 (3)6 (6)
 Dyspnoea0 (0)4 (4)7 (7)
 Gastrointestinal complaints57 (63)59 (63)41 (42)
 Infection12 (13)21 (23)22 (23)
 Skin problems20 (22)25 (27)27 (28)
 Hair loss8 (8)7 (8)14 (14)
 Hearing loss1 (1)0 (0)0 (0)
 Visual impairment7 (8)17 (18)7 (7)
 Hyperglycaemia0 (0)1 (1)0 (0)
 Feeling ‘sad’7 (8)13 (14)12 (12)
 Sleep disorder4 (4)13 (14)8 (8)
 Bone marrow depression17 (19)8 (9)7 (7)
 High creatinine2 (2)6 (6)4 (4)
 Elevated liver enzymes12 (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.