Background Methotrexate (MTX) is still a mainstay in the therapy of rheumatoid arthritis (RA) in the era of biologics therapy, and some patients do respond well without radiographic progression to MTX monotherapy on individual basis. According to O'Dell et al., initial MTX monotherapy with the option step-up to combination therapy indicates that approximately 30% of patients fare well with MTX monotherapy (Ref 1). However, the discriminant identifying the subgroup with radiographic non-progression remains unclear and thus, predicting at the outset such patient subgroup would be highly rewarding clinically.
Objectives To evaluate clinical efficacy of low-dose MTX monotherapy unique to Japan, and discover a predictor identifying a subgroup of RA patients with radiographic non-progression.
Methods Clinical measure including disease activity score 28 (DAS28), modified health assessment of questionnaire (mHAQ) and others in rheumatoid patients continuously treated with MTX monotherapy (n=161) was compared with radiographic year-progression of van der Heijde modified total Sharp score (ΔTSS), by classifying the patients into subgroups with structural remission (REM; ΔTSS≤0.5), clinically relevant radiographic progression (CRRP; ΔTSS>3) and rapid radiographic progression (RRP; ΔTSS>5) prospectively for 3 yrs.
Results Disease activity was improved yearly from baseline to 3yrs: DAS28-ESR (3) from 5.2±1.1 to 3.9±1.7, %DAS28 remission from 1% to 19%, mHAQ from 0.54±0.47 to 0.18±0.32, %mHAQ remission from 16% to 60%, and Boolean remission from 0.8% to 24.0%. As to radiographic progression, the patients classified to REM were increased from 62/161 (38.5%) to 69/137 (50.4%) (p=0.0466), as compared with 55/161 (34.2%) to 28/137 (20.4%) of CRRP (p=0.0095) and 35/161 (21.7%) to 15/137 (10.9%) of RRP (p=0.0019) patients. Receiver operating characteristic (ROC) analysis revealed lower baseline and annual serum MMP3 as a predictor identifying a subgroup of patients with radiographic non-progression: the patients containing baseline serum MMP3 levels below 103.7 ng/ml were classified to neither CRRP nor RRP, with negative predictive values (NPV) 88.7% and 96.8%, respectively (Fig.1). This baseline cut-off level was applicable to succeeding 1∼2 or 2∼3 yrs of MTX monotherapy, with NPV 88.1% or 87.9% (CRRP) and 87.8% or 91.0% (RRP), respectively, and also when male and female patients were studied separately.
Conclusions Under low-dose MTX monotherapy, approximately half of Japanese rheumatoid patients maintained structural remission, and this radiographic non-progression was predictable by lower levels of serum MMP-3 at the outset.
JR O'Dell, et al. Arthritis Rheum 65:1985,2013.
Disclosure of Interest None declared