75 Prevention of rheumatoid arthritis Glucocorticoids Glucocorticoid are immunosuppressive and anti-inflammatory drugs which inhibit leukocyte migration to the site of inflammation and production of pro-inflammatory cytokines and soluble factors [40]. Glucocorticoids are used as first line medication in the treatment of RA, especially as bridging and/or local therapy in combination with cDMARDs [41,42]. They are also frequently used during flares, given their rapid immunosuppressive action [43]. Side effects are dose- and time-dependent, and accordingly short-term and/or low dose administration of glucocorticoids (≤ 5 mg/ day) is associated with a lower risk of side-effects [43,44]. Therefore, the European Alliance of Associations for Rheumatology (EULAR) recommendations for the use of glucocorticoids advocate tapering as soon as possible [41]. In case of long-term use, a low dose (≤ 5 mg/day) is preferred [45]. The Stop Arthritis Very Early (SAVE) trial investigated the efficacy of glucocorticoids in patients with early inflammatory arthritis of >1 joint. Patients were included if symptom duration was less than 16 weeks, and based on the number of swollen joints stratified into either monoarthritis or oligoarthritis (≤ 3 swollen joints) or polyarthritis (> 3 swollen joints). Subsequently, patients were treated with either a single intramuscular injection of 120 mg methylprednisolone or placebo (NaCl 0.9%). Paracetamol and/or non-steroidal anti-inflammatory drugs (NSAIDs) could be taken on demand. Patients were followed up for one year and the study’s primary outcome was the presence of clinical remission at 12 weeks and at 52 weeks after injection, defined as the absence of joint swelling, not more than two tender joints and normalized CRP without additional glucocorticoid or DMARD treatment. A total of 383 individuals were included in the study and randomized to treatment (198 patients, 51.7%) vs. placebo (185 patients, 48.3%). No significant difference was found in the percentage of patients who reached remission in the two groups (16.2% in the treatment group vs. 17.8% in the placebo group). Moreover, no difference was found in the percentage of patients who required additional glucocorticoids (24.4% vs. 27.0%, respectively) or DMARDs (43.4% vs. 46.5%, respectively) in the two groups. Patients with monoarthritis had a statistically higher percentage of remission (27.7%) and lower symptom duration than patients with polyarthritis (10.2%), while no significant difference was found between the treatment groups [46]. The dexamethasone trial by Bos et al. recruited patients with arthralgia who had at least a two-fold increased level of IgM-RF and/or ACPA measured at least twice with an interval of more than 4 weeks. Patients were only included if positive for HLA-DR SE and were excluded in case of active hepatitis C and/or EBV infection, 4
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