Structural joint damage and hand bone loss in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by pain, swelling and progressive destruction of the joints leading to loss of function and invalidity. The bone destruction in RA is characterised by two distinct features: structural joint damage and hand bone loss, and their prevention is an important treatment goal. Inhibitors of tumour necrosis factor alpha (TNF-inhibitors) have markedly improved the treatment options in RA patients who fail treatment with conventional synthetic Disease Modifying Anti Rheumatic Drugs (sDMARDS), but their effectiveness with regards to structural joint damage and hand bone loss, predictors thereof and the association with disease activity during treatment have mainly been investigated in randomized controlled trials (RCTs) with limited generalizability due to strict in- and exclusion criteria. The main aim of the PhD thesis was to assess and predict structural joint damage and hand bone loss in patients with early and established RA treated with sDMARDs and TNF-inhibitors. This was investigated in two cohorts: A) The "DANBIO X-ray study": an observational, nationwide, longitudinal cohort study of established RA patients treated in clinical practice who initiated TNF-inhibitor treatment after failure of sDMARDs and B) The "OPERA study": a randomized controlled trial of sDMARD-naïve patients with early RA treated with methotrexate (MTX) and intraarticular glucocorticoid injections in combination with adalimumab or placebo-adalimumab. Structural joint damage progression was assessed with the Sharp/van der Heijde radiographic method and hand bone loss was assessed with Digital X-ray Radiogrammetry. From the studies presented in the PhD thesis the following was concluded: Structural joint damage progression and hand bone loss were significantly lower during two years of TNF-inhibitor treatment compared to the previous two years of sDMARD-treatment in the DANBIO X-ray Study. The majority of patients had no progression of structural joint damage during two years of TNF-inhibitor treatment, while hand bone loss remained increased compared to reference values from the general population in the majority of patients. Adalimumab had no impact on hand bone loss in the OPERA study. Existing structural joint damage, older age, IgM-rheumatoid factor positivity and concomitant treatment with prednisolone were independent predictors of progression in structural joint damage in the DANBIO X-ray cohort, while high hand bone loss in the first 6 months of treatment and placebo treatment were independently associated with increase in structural joint damage scores in the OPERA study. A high hand bone mass and disease activity were independent predictors of increased hand bone loss in the DANBIO X-ray study, while older age and high functional disability predicted hand bone loss in the OPERA study. High disease activity during treatment was associated with structural joint damage progression during TNF-inhibitor treatment in the DANBIO X-ray study and with hand bone loss in the DANBIO X-ray and OPERA studies.