Background
Methods
Study design
Patients and randomisation
Procedures of the study
Endpoints
Statistical analysis
Results
Demographic data and patient flow
IFX + MTX | MTX | PL | P value | |
---|---|---|---|---|
Number of patients (n) | 38 | 36 | 16 | 0.4440 |
Female | 26 (68.4%) | 28 (77.8%) | 9 (56.3%) | 0.2833 |
Age (years), mean ± SD | 52.1 ± 14.1 | 52.9 ± 14.0 | 54.4 ± 11.2 | 0.9170 |
Symptom duration (weeks)a, mean ± SD | 10.3 ± 2.3 | 9.4 ± 2.3 | 9.8 ± 1.8 | 0.0722 |
Rheumatoid factor positive | 13 (34.2%) | 13 (36.1%) | 7 (43.8%) | 0.7988 |
Patients who used steroids prior to the study | 24 (63.2%) | 22 (61.1%) | 9 (56.3%) | 0.8931 |
Anti-citrullinated protein antibody positive | 18 (47.4%) | 16 (44.4%) | 7 (43.8%) | 0.9563 |
Patients who meet the ACR/EULAR 2010 classification criteria for RA, 2010 [25] | 26 (68%) | 19 (53%) | 12 (75%) | 0.2135 |
Patients who meet the 1987 ARA classification criteria for RA [35] | 22 (58%) | 19 (53%) | 9 (56%) | 0.9049 |
Health Assessment Questionnaire (0–3) | 0.9 ± 0.7 | 0.9 ± 0.6 | 0.7 ± 0.7 | 0.2903 |
Disease Activity Score 28 (DAS28; based on ESR) | 5.0 ± 1.4 | 4.8 ± 1.3 | 4.7 ± 1.1 | 0.8464 |
Simplified Disease Activity Index (SDAI) | 34.3 ± 23.8 | 31.1 ± 14.4 | 27.5 ± 20.0 | 0.4771 |
Clinical Disease Activity Index (CDAI) | 25.1 ± 14.7 | 26.2 ± 13.9 | 23.5 ± 11.9 | 0.8951 |
Swollen joint count (0–28) | 7.2 ± 5.7 | 6.50 ± 5.1 | 7.4 ± 4.6 | 0.7048 |
Tender joint count (0–28) | 9.2 ± 7.3 | 10.3 ± 7.2 | 7.8 ± 5.6 | 0.5263 |
Visual analogue scale pain (mm) | 44.0 ± 29.3 | 44.2 ± 24.3 | 44.6 ± 22.7 | 0.9595 |
Patient global assessment (mm) | 48.6 ± 29.0 | 47.8 ± 24.7 | 39.6 ± 21.0 | 0.5274 |
Evaluator/physician global assessment (mm) | 38.6 ± 18.3 | 46.3 ± 22.3 | 44.6 ± 20.7 | 0.3627 |
C-reactive protein (mg/dl) | 1.71 ± 2.40 | 1.18 ± 1.88 | 0.98 ± 1.28 | 0.5567 |
Erythrocyte sedimentation rate (ESR; mm/h) | 23.2 ± 20.3 | 20.3 ± 21.2 | 20.4 ± 12.6 | 0.8129 |
Total Sharp-van-der-Heide score | 2.8 ± 5.4 | 3 ± 3.8 | 4.6 ± 8.6 | 0.4816 |
Erosion score | 1.2 ± 1.8 | 1.6 ± 2.2 | 2.2 ± 4.2 | 0.6019 |
Joint space narrowing score | 1.6 ± 3.8 | 1.4 ± 2.2 | 2.4 ± 4.4 | 0.5658 |
IFX + MTX n = 38 | MTX n = 36 | PL n = 16 | |
---|---|---|---|
Clinical remission (primary endpoint), no. of patients in remission (%) | |||
6 months | 10 (26%) | 6 (17%) | 0 |
1 year | 12 (32%) | 5 (14%) | 0 |
2 years | 9 (24%) | 1 (3%) | 3 (19%) |
Other definitions of remission, no. of patients in remission (%) | |||
Disease Activity Score 28 (DAS28) | |||
6 months | 20 (53%) | 11 (31%) | 1 (6%) |
1 year | 24 (63%) | 13 (36%) | 3 (19%) |
2 years | 23 (61%) | 11 (31%) | 5 (31%) |
Simplified Disease Activity Index (SDAI) | |||
6 months | 16 (42%) | 9 (25%) | 1 (6%) |
1 year | 18 (47%) | 13 (36%) | 1 (6%) |
2 years | 18 (47%) | 13 (36%) | 4 (25%) |
ACR/EULAR Boolean | |||
6 months | 15 (40%) | 8 (22%) | 0 |
1 year | 13 (34%) | 9 (25%) | 1 (6%) |
2 years | 13 (34%) | 10 (28%) | 4 (25%) |
ACR improvement, responders | |||
ACR20 | |||
6 months | 20 (53%) | 18 (50%) | 4 (25%) |
1 year | 22 (58%) | 22 (61%) | 3 (19%) |
2 years | 19 (50%) | 19 (53%) | 3 (19%) |
ACR50 | |||
6 months | 16 (42%) | 13 (36%) | 1 (6%) |
1 year | 17 (45%) | 16 (44%) | 3 (19%) |
2 years | 14 (37%) | 15 (42%) | 3 (19%) |
ACR70 | |||
6 months | 15 (40%) | 6 (17%) | 1 (6%) |
1 year | 14 (37%) | 11 (31%) | 2 (13%) |
2 years | 13 (34%) | 11 (31%) | 3 (19%) |
Other secondary outcome parameters (mean ± SD) | |||
Pain | |||
6 months | 17.3 ± 20.3 | 22.5 ± 25.2 | 42.7 ± 31.0 |
1 year | 20.9 ± 23.8 | 18.3 ± 25.3 | 45.7 ± 31.8 |
2 years | 23.0 ± 25.1 | 23.3 ± 29.8 | 43.5 ± 32.8 |
Swollen joints (28 joints) | |||
6 months | 2.3 ± 5.2 | 2.1 ± 4.5 | 4.9 ± 5.6 |
1 year | 2.3 ± 5.2 | 2.1 ± 4.3 | 5.0 ± 5.6 |
2 years | 2.8 ± 5.6 | 2.4 ± 4.5 | 5.1 ± 5.6 |
Tender joints (28 joints) | |||
6 months | 2.9 ± 5.9 | 4.9 ± 6.2 | 7.0 ± 6.4 |
1 year | 2.5 ± 5.6 | 4.2 ± 6.0 | 7.2 ± 6.8 |
2 years | 3.4 ± 6.5 | 4.0 ± 6.1 | 7.1 ± 7.0 |
Patient global visual analogue scale (VAS; mm) | |||
6 months | 17.7 ± 6.5 | 23.1 ± 24.6 | 35.1 ± 28.2 |
1 year | 21.2 ± 24.0 | 18.4 ± 24.7 | 38.0 ± 29.3 |
2 years | 24.3 ± 25.3 | 24.8 ± 30.0 | 35.6 ± 29.5 |
Evaluator global VAS (mm) | |||
6 months | 16.1 ± 22.0 | 17.2 ± 24.1 | 34.6 ± 28.0 |
1 year | 14.1 ± 20.8 | 17.7 ± 24.6 | 39.3 ± 29.8 |
2 years | 16.6 ± 24.1 | 18.4 ± 24.7 | 34.5 ± 31.3 |
C-reactive protein (mg/dl) | |||
6 months | 0.5 ± 0.9 | 0.6 ± 1.0 | 0.8 ± 0.9 |
1 year | 0.5 ± 0.9 | 0.5 ± 1.0 | 0.7 ± 0.8 |
2 years | 0.6 ± 1.1 | 0.6 ± 1.0 | 0.5 ± 0.8 |
Erythrocyte sedimentation rate (mm) | |||
6 months | 14.6 ± 12.2 | 17.8 ± 12.5 | 14.9 ± 6.9 |
1 year | 14.6 ± 12.3 | 18.7 ± 13.0 | 18.3 ± 9.7 |
2 years | 16.5 ± 14.1 | 17.6 ± 11.2 | 16.5 ± 10.7 |
Health Assessment Questionnaire (HAQ) | |||
6 months | 0.30 ± 0.45 | 0.57 ± 0.64 | 0.54 ± 0.67 |
1 year | 0.33 ± 0.46 | 0.52 ± 0.62 | 0.61 ± 0.66 |
2 years | 0.41 ± 0.52 | 0.58 ± 0.61 | 0.62 ± 0.65 |
X-raysa | |||
6 months | −0.02 ± 0.88 | 0.07 ± 0.23 | 0.41 ± 1.53 |
1 year | 0.18 ± 1.06 | 0.16 ± 0.44 | 0.0 ± 0.41 |
2 years | 0.36 ± 0.95 | 0.28 ± 0.67 | 0.63 ± 1.31 |
Clinical remission at 1 year
Clinical remission at the end of year 2
Changes in disease activity and core set variables
Patients classified as RA or non-RA at baseline
Radiographic changes
Adverse events
Total n = 90 | IFX + MTX n = 38 | MTX n = 36 | PL n = 16 | |
---|---|---|---|---|
Adverse events, n (%) | ||||
Infectious/parasitic disease | 31 (35%) | 19 (50%) | 9 (25%) | 3 (19%) |
Malignancy | 1 (1%) | 0 | 1 (3%) | 0 |
Disease of blood, blood-forming organs, and immune mechanisms (except arthritis) | 1 (1%) | 1 (3%) | 0 | 0 |
Endocrine, nutritional, and metabolic diseases | 9 (10%) | 2 (5%) | 5 (14%) | 2 (12%) |
Disease of the nervous system | 17 (19%) | 6 (16%) | 9 (25%) | 2 (13%) |
Diseases of the eye | 3 (3%) | 1 (3%) | 2 (6%) | 0 |
Diseases of circulatory system | 16 (18%) | 6 (16%) | 7 (19%) | 3 (19%) |
Diseases of respiratory system | 43 (48%) | 23 (61%) | 16 (44%) | 4 (25%) |
Diseases of the digestive system | 37 (41%) | 15 (39%) | 17 (47%) | 5 (31%) |
Diseases of the skin and subcutaneous tissue | 25 (28%) | 12 (32%) | 8 (22%) | 5 (31%) |
Diseases of musculoskeletal system and connective tissue | 30 (33%) | 15 (39%) | 9 (25%) | 6 (38%) |
Diseases of urogenital system (pregnancy, childbirth, and puerperium) | 4 (4%) | 2 (5%) | 2 (6%) | 0 |
Symptoms, signs, and abnormal clinical and laboratory findings not elsewhere classified | 27 (30%) | 11 (29%) | 11 (31%) | 5 (31%) |
Injury, poisoning and certain other consequences of external causes | 9 (10%) | 6 (16%) | 3 (8%) | 0 |
External causes of morbidity | 1 (1%) | 1 (3%) | 0 | 0 |
Total | 120 | 99 | 35 | |
SAEs (n = 12) | ||||
Hospitalisation due to different reasonsa | 4 | 1 | 3 | |
Fainted during blood collection prior to administration of study drug | 1 | 0 | 0 | |
Significantly raised transaminase levels | 1 | 0 | 0 | |
Hematuria, followed by a diagnosis of bladder cancer | 0 | 1 | 0 | |
Hypertensive episode 1 h after the last infusion with study drug | 0 | 1 | 0 |