Background/Purpose: To prevent disease progression, treat-to-target recommendations for rheumatoid arthritis (RA) include the evaluation and adjustment of drug therapy at least every 3 months until a target level of remission or low disease activity is achieved.  It is well established that anti-tumor necrosis factor (TNF) treatment modifies associations between disease activity and radiographic progression over periods of 1-2 years.¹  We aimed to assess whether TNF inhibition modifies this association over the initial 3-6 months of treatment for early RA. 

Methods: Methotrexate (MTX)-naïve early RA patients randomized to double-blind treatment with adalimumab (ADA)+MTX combination therapy vs. MTX monotherapy were drawn from the Phase III PREMIER clinical trial.  Associations between week 12 disease activity, assessed using DAS28-CRP(4), and changes in modified total sharp score (mTSS) from baseline to week 26 were compared between the ADA+MTX and MTX arms using generalized additive regression.  mTSS progression was modeled as an absolute score change and as a worsening of ≥5 units.²  Models were fit with and without adjustment for baseline mTSS, DAS28, numbers of tender and swollen joints, and RA duration.

Results: A total of 219 MTX-treated patients and 241 ADA+MTX-treated patients were included in the investigation. The mean age was 52 years, 73% were female, and the average RA duration was 9 months.  In the adjusted analyses, patients treated with ADA+MTX experienced limited mean increases in mTSS from baseline to week 26 that were numerically similar across all levels of week 12 DAS28, whereas patients treated with MTX showed a sharp increase in mTSS progression with increasing week 12 DAS28 (Figure).  Compared to patients who were treated with MTX alone, those treated with ADA+MTX achieving a DAS28 £2.6 at week 12 had a significantly smaller change in mTSS (difference: -1.59; 95% CI: -2.74, -0.44) and a significantly lower risk of mTSS progression of ≥5 units (odds ratio [OR]: 0.19; 95% CI: 0.06, 0.61) at week 26.  Results were similar for unadjusted analyses.  

Conclusion: Early RA patients achieving a given disease activity level by week 12 with ADA+MTX experience less radiographic progression by week 26 than those achieving the same disease activity level with MTX alone.  This could reflect the slower onset of response to MTX and/or a separate structure-protective effect for anti-TNF treatment.  These aspects should be considered when setting disease activity targets with the goal of limiting radiographic progression.   

References:

1.     Emery P et al. Journal of Rheumatology. 2009; 36(6): 1429-1441.

2.     Bruynesteyn et al. Arthritis and Rheumatism. 2002; 46(4): 913-920.