Discontinuation of infliximab and potential predictors of persistent low disease activity in patients with early rheumatoid arthritis and disease activity score-steered therapy: subanalysis of the BeSt study.

OBJECTIVE: To describe the disease course after the cessation of infliximab in early rheumatoid arthritis patients with disease activity score (DAS)-steered treatment and to identify predictors of persistent low disease activity. METHODS: In a post-hoc analysis of the BeSt study, disease activity and joint damage progression were observed in patients treated with methotrexate plus infliximab, who discontinued infliximab after achieving low disease activity (DAS ≤2.4) for 6 months. Predictors were identified using Cox regression analysis. RESULTS: 104 patients discontinued infliximab, of whom 77 had received infliximab plus methotrexate as initial treatment. Mean DAS at the time of infliximab cessation was 1.3, median symptom duration was 23 months and median Sharp/van derHeijde score was 5.5. The median follow-up was 7.2 years. Infliximab was re-introduced after loss of low disease activity in 48%, after a median of 17 months. The joint damage progression rate did not increase in the year after cessation, regardless of flare. After re-introduction of infliximab, 84% of these patients again achieved a DAS ≤2.4. In the multivariable model, smoking, infliximab treatment duration ≥18 months and shared epitope (SE) were independently associated with the re-introduction of infliximab: 6% of the non-smoking, SE-negative patients treated <18 months needed infliximab re-introduction. CONCLUSION: Cessation of infliximab was successful in 52%, with numerically higher success rates in patients initially treated with infliximab. Of the 48% who flared, 84% regained low disease activity. The joint damage progression rate did not increase in the year after cessation. Smoking, long infliximab treatment duration and SE were independently associated with re-introduction of infliximab.

Clinical synovitis in a particular joint is associated with progression of erosions and joint space narrowing in that same joint, but not in patients initially treated with infliximab.

OBJECTIVES: To assess the relationship between joint tenderness, swelling and joint damage progression in individual joints and to evaluate the influence of treatment on these relationships. METHODS: First-year data of the Behandel Strategieën (BeSt) study were used, in which patients recently diagnosed as having rheumatoid arthritis (RA) were randomly assigned into four different treatment strategies. Baseline and 1-year x-rays of the hands and feet were assessed using the Sharp-van der Heijde score (SHS). With generalised estimating equations, 3-monthly assessments of tender and swollen joints of year 1 were related to erosion progression, joint space narrowing (JSN) progression and total SHS progression at the individual joint level (definition > 0.5 SHS units) in year 1, corrected for potential confounders and within-patient correlation for multiple joints per patient. RESULTS: During year 1, 59% of all 13 959 joints analysed were ever tender and 45% ever swollen, 2.1% showed erosion progression, 1.9% JSN progression and 3.6% SHS progression. Swelling and tenderness were both independently associated with erosion and JSN progression with comparable OR, although with higher OR in the hands than in the feet. Local swelling and tenderness were not associated with local damage progression in patients initially treated with infliximab. CONCLUSION: Clinical signs of synovitis are associated with erosion and JSN progression in individual joints after 1 year in RA. A disconnect between synovitis and joint damage progression was observed at joint level in patients who were treated with methotrexate and infliximab as initial treatment, confirming the disconnect between synovitis and the development of joint damage in tumour necrosis factor blockers seen at patient level.

Changes in bone mineral density in patients with recent onset, active rheumatoid arthritis.

OBJECTIVES: We examined the effects of four different treatment strategies on bone mineral density (BMD) in patients with recently diagnosed, active rheumatoid arthritis (RA) and the influence of disease-related and demographic factors on BMD loss after 1 year of follow-up in the BeSt trial. METHODS: BMD measurements of the lumbar spine and total hip were performed in 342 patients with recent onset RA at baseline and after 1 year. Multivariable regression analyses were performed to determine independent associations between disease and demographic parameters and BMD loss after 1 year. RESULTS: Median BMD loss after 1 year was 0.8% and 1.0% of baseline in the spine and the hip, respectively. No significant differences between the treatment groups, including corticosteroids and the anti-tumour necrosis factor-alpha infliximab, were observed with regard to BMD loss after 1 year of treatment. Joint damage at baseline and joint damage progression according to the Sharp-van der Heijde score were independently associated with more BMD loss after 1 year. The use of bisphosphonates independently protected against BMD loss. CONCLUSIONS: After 1 year of follow-up in the BeSt study, we did not find differences in BMD loss between the four treatment strategies, including high doses of corticosteroids and anti-tumour necrosis factor-alpha. Joint damage and joint damage progression are associated with high BMD loss, which emphasises that BMD loss and erosive RA have common pathways in their pathogenesis.