Background/Purpose: In early rheumatoid arthritis (RA), starting therapy as soon as possible is important to reduce disease activity and preserve the joints. With application of biological disease modifying anti-rheumatic drugs (DMARDs), a remarkable gain is achieved in prevention of joint damage. Although with initiation of methotrexate (MTX) as only DMARD many patients achieve the treatment target of clinical remission, a large proportion (~30%) of them still shows radiographic progression as a result of ongoing subclinical inflammation. The aim of this study was to analyze whether tocilizumab (TCZ) in DMARD-naïve patients with early RA would result in significantly less joint damage when compared to a step-up methotrexate-based strategy and whether this would involve erosions and/or joint space narrowing (JSN) scores.

Methods: In U-Act-Early, patients initiated TCZ plus MTX, TCZ, or MTX therapy and were treated to target until sustained remission (defined as disease activity score assessing 28 joints (DAS28) <2.6 with ≤4 swollen joints for ≥24 weeks) was achieved. If no remission, hydroxychloroquine was added. Hereafter, if the target still was not achieved, the initial strategy ended and the subsequent strategy started; patients randomized to the TCZ or MTX arm switched to TCZ+MTX therapy. Those who initially started with this combination therapy switched to the standard of care (e.g. MTX combined with a tumor necrosis factor inhibitor). If sustained remission was achieved, medication was tapered and stopped. The Sharp-van der Heijde score (SHS) was used to evaluate radiographic progression; erosion and joint space narrowing (JSN) scores were also assessed separately. Furthermore, a computerized method was used to confirm the findings in JSN in the hand as evaluated by the SHS. Non-parametric testing was used to evaluate between-group differences as damage scores were not normally distributed.

Results: In total, 317 DMARD-naïve patients with early RA were randomized; 106 to the TCZ+MTX arm, 103 to the TCZ arm, and 108 to the MTX arm (Table). For changes from baseline in SHS, significantly lower scores when compared to the MTX arm were found in the TCZ+MTX arm after 52 weeks (p=0.02); after 104 weeks the difference compared with the MTX arm was significant for both TCZ strategies (TCZ+MTX, p=0.02; TCZ, p=0.04). For erosions, significant between-group differences were noted after 104 weeks in favor of the TCZ strategies (TCZ+MTX vs. MTX, p=0.02; TCZ vs MTX, p=0.02). However, for JSN, no significant differences were found between the strategies during follow-up (p≥0.20), which was in accordance with the findings of the computerized method (p≥0.09) and data from literature.

Conclusion: Initiation of a tocilizumab-based strategy in DMARD-naïve patients with early RA results in significantly less progression of erosive radiographic joint damage when compared to a step-up methotrexate-based strategy, improving long-term clinical outcome.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-inhibits-progression-of-erosive-joint-damage-in-early-rheumatoid-arthritis-more-effectively-than-step-up-methotrexate-therapy/