Overview of RCTs comparing early versus delayed DMARD initiation in patients with UA in order to prevent RA development
| First author, year of publication | Type of trial | Quality score* (%) | Patients | N | Follow-up time | Intervention | Control | Outcome of interest | Relevant result | Association between early DMARD intervention and outcome |
| van Dongen, 2007,76 PROMPT trial | Randomised, double-blind placebo-controlled trial. | 93 | Probable RA (1958 criteria), not fulfilling the 1987 criteria for RA. | 110 (55/55) | 30 months | Up to 30 mg of MTX/week. | Up to 30 mg placebo/week. | Fulfilment of the 1987 criteria for RA. | After 30 months, 40% in intervention arm and 53% in control arm fulfilled the 1987 criteria (not statistically significant). Time to RA development significantly longer in intervention arm (p=0.04). | NS |
| Saleem, 200875 | Randomised, double-blind placebo-controlled trial. | 64 | Poor prognosis UA <12 months’ symptom duration. | 17 (10/7) | 52 weeks | Infliximab 3 mg/kg for 14 weeks. | Placebo 3 mg/kg for 14 weeks. | Fulfilment of the 1987 criteria for RA. | At week 52, 17/17 (100%) of patients developed RA. | NS |
| Verstappen, 2010,79 STIVEA trial | Randomised, double-blind placebo-controlled trial. | 93* | Inflammatory polyarthritis small joints, symptom duration 4–10 weeks. | 265 (133/132) | 12 months | 3× 80 mg intramuscular methylprednisolone acetate at 0, 1 and 2 weeks. | 3× placebo intramuscularly at 0,1 and 2 weeks. | Clinical diagnosis of RA. | Clinical diagnosis of RA in 60.4% of patients in control arm, vs 48.6% in intervention arm (p=0.145). | NS |
| Machold, 2010,80 SAVE trial | Randomised, double-blind placebo-controlled trial. | 79 | Inflammatory arthritis, symptom duration <16 weeks. | 383 (198/185) | 52 weeks | 1× 120 mg methylprednisolone intramuscularly. | 1× placebo (NaCl) intramuscularly. | Clinical diagnosis of RA. | Proportions of patients developing RA were similar in the intervention arm and control arm (45.1% vs 50.7%, p=0.36). | NS |
| Emery, 2010,78 ADJUST trial | Randomised, double-blind placebo-controlled trial. | 71 | 1–3/7 points 1987 criteria, arthritis ≥2 joints, ACPA-positive, symptom duration <18 months. | 56 (28/28) | 1 year | Abatacept ~10 mg/kg for 6 months. | Placebo ~10 mg/kg for 6 months. | Fulfilment of the 1987 criteria for RA. | At year 1, 46.2% in the intervention arm vs 66.7% in the control arm fulfilled the 1987 criteria for RA (difference −20.5%, 95% CI −47.4% to 7.8%). | NS |
| van Aken, 2014,77† PROMPT trial | Randomised, double-blind placebo-controlled trial. | 93 | Probable RA (1958 criteria), not fulfilling the 1987 criteria for RA. | 110 (55/55) | 30 months | Up to 30 mg of MTX/week. | Up to 30 mg placebo/week. | Fulfilment of the 1987 criteria for RA. | After 5 years, 45% in intervention arm and 53% in control arm fulfilled the 1987 criteria (p=0.45). | NS |
*Studies with a quality score ≥75% were considered high-quality studies.
†This study reports on the same population as a previous study by van Dongen etal.76
ACPA, anticitrullinated protein antibody;ADJUST, Abatacept study to Determine the effectiveness in preventing the development of rheumatoid arthritis in patients with Undifferentiated inflammatory arthritis and to evaluate Safety and Tolerability; DMARD, disease-modifying antirheumatic drug;MTX, methotrexate;NS, not significant;NaCl, Natrium Chloride; PROMPT, probable rheumatoid arthritis treated with methotrexate or placebo; RA, rheumatoid arthritis;RCT, randomised controlled trial;SAVE, stop arthritis very early; UA, undifferentiated arthritis.