Background The presence of systemic extra-articular manifestations (EAM) of rheumatoid arthritis (RA) is a sign of higher clinical and laboratory activities associated with the presence and high titers of rheumatoid factor (RF) and antibodies to cyclic citrullinated peptides (anti-CCP), a higher rate of radiological progression . However, the effectiveness of certain DMARD in pts with EAM is not sufficiently investigated.
Objectives to evaluate the effectiveness of metotrexate (MTX), leflunomide (LF), sulfasalazine (SS) and combination basic therapy (CBT) in ExRA.
Methods 336 pts with RA (45.4% with early RA) were studied. Mean age at inclusion was 50.4±0.63 yrs, mean disease duration – 51.5±3.31 mths. 78.9% of the pts were women; 62.6% were positive for RF and 75.7% - for anti-CCP. In 146 pts (43.5%) EAM of RA were observed: most often - rheumatoid nodules (RN) -22.1%, lymphadenopathy (LAP) - 13.3%, systemic features (weight loss and fever) - 10.1%, and less frequently - Sjögren’s syndrome, vasculitis, eye disease, serositis and others. Pts were treated with a mean dose of 13.6±0.30 mg/week MTX (n=91), mean dose of 19.2±0.28mg/d LF (n=95), dose of SS 2.0 g/d (n=76) or CBT (MTX+LF, MTX+SS, LF+SS, MTX or LF or SS + hydroxychloroquine; n=74). In all groups, glucocorticoids were received by 72.4% - 80.3% of pts. Groups were comparable by average levels of disease activity score (DAS28) and radiologic changes measured by modifiedSharp-van der Heijde score (SHS). Effectiveness outcomes were evaluated after 2 yrs of treatment by ΔDAS28 and ΔSHS.
Results Before study, all groups were similar in number of pts with EAM and varied from 41.7% to 50.0% of pts. Use of LF caused reduction/disappearance of RN more often (in 65.2% pts) than MTX (in 34.4%), SS (in 15.4%) or CBT (in 31.2%) (p<0.05). Appearance of new RN was observed in 19 pts receiving MTX, in 3 pts receiving SS or CBT and in none treated with LF (p<0.01 vs MTX). Disappearance of LAP occurred in: 25.0% pts in MTX group, 56.2% pts in LF group (p<0.01 vs MTX), 30.8% and 33.3% pts in SS and CBT groups respectively.
After 2 yrs of treatment, all therapeutic strategies had equal effect on reduction of clinical activity (ΔDAS28) and radiologic progression (ΔSHS) in pts without EAM. Pts with EAM had lowest ΔDAS28 in case of SS receiving (1.50±0.27) compared to MTX (2.34±0.23), LF (2.55±0.25) and CBT (2.57±0.23) (p<0.05 vs LF, MTX and CBT). Radiographic progression was significantly higher in MTX (13.7±1.84) and SS (15.9±2.27) groups with EAM than without EAM (7.41±1.27 and 7.84±2.03 respectively), while efficacy of LF and CBT was not dependent on the presence of EAM. Pts with EAM had more significant radiologic progression when received SS or MTX (p<0.05 vs LF-7.33±2.0 and CBT-8.08±1.56).
Conclusions All therapeutic strategies have equal efficacy on reduction of clinical activity and radiologic progression in pts without EAM. Effects of LF and CBT on clinical activity and dynamics of radiologic changes do not depend on the presence of EAM. Pts with EAM have more significant radiologic progression when receiving SS or MTX compared to LF and CBT and to pts without EAM receiving SS or MTX.
Turesson C. et al. Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis // Ann Rheum Dis 2007;66:59-64.
Disclosure of Interest None Declared