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Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its anti-inflammatory effects: disassociation of the link between inflammation and destruction
  1. Josef S Smolen1,2,
  2. José C Martinez Avila1,
  3. Daniel Aletaha1
  1. 1Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
  2. 22nd Department of Medicine, Center of Rheumatic Diseases, Hietzing Hospital, Vienna, Austria
  1. Correspondence to Josef S Smolen, Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; josef.smolen{at}wienkav.at

Abstract

Background Treatment with tumour necrosis factor inhibitors (TNF-i) plus methotrexate (MTX), but not MTX monotherapy alone, inhibits joint damage progression even at higher levels of disease activity. Such disassociation of disease activity and structural damage has not been shown for biological agents other than TNF-i.

Objectives To evaluate whether interleukin 6 (IL-6) inhibition with tocilizumab (TCZ) interferes with joint destruction beyond its effects on disease activity.

Methods A random 90% sample of data from the (The Tocilizumab Safety and the Prevention of Structural Joint Damage Study) LITHEtrial on active rheumatoid arthritis (RA) despite MTX was used, which compared addition of placebo (n=117) with addition of TCZ (n=414) every 4 weeks. Baseline and 1-year values of clinical and serological variables were correlated with changes to 1 year of the total Genant-modified Sharp score (TGSS) using a Spearman test, and the progression of TGSS, erosion and joint space narrowing (JSN) scores in groups with low and high disease activity were compared for placebo and TCZ (Kruskal–Wallis).

Results Baseline variables were similar among the groups. Change of TGSS was lower in patients receiving TCZ than placebo (TCZ: 0.29±0.96; placebo: 0.90±1.92; p=0.0007). In patients receiving placebo, the correlation with TGSS change was significant for baseline scores of the simplified disease activity index (SDAI; r=0.18, p=0.047) and swollen joint count 28 (r=0.22, p=0.019), with similar trends for C-reactive protein. Similar correlations were seen for SDAI, clinical disease activity index, disease activity score 28 at 1 year with x-ray change during that year (r=0.26–0.28, p=0.002–0.006). In contrast, none of the baseline or 1-year variables showed significant correlation with x-ray changes in patients receiving TCZ+MTX, suggesting a disassociation of the link between disease activity and damage by TCZ. Finally, for patients in remission or with low disease activity, progression of TGSS, erosion and JSN was similar among treatment groups (TGSS: placebo, 0.4±1.1; TCZ, 0.2±0.7; p=NS), while for patients with moderate or high disease activity placebo-treated patients progression was significantly greater (TGSS: 1.2±2.2 vs 0.4±1.2; p=0.0009).

Conclusions IL-6 inhibition with TCZ plus MTX retards joint damage progression independently of its impact on disease activity. Similar effects have hitherto been reported only for TNF-i. This indicates that the effects of IL-6 inhibition on progression of joint damage in RA are among the most profound currently attainable.

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl

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Footnotes

  • Funding The study was partly supported by a grant from Roche and partly supported through Coordination Theme 1 (Health) of the European Community's FP7; grant agreement number HEALTH-F2-2008–223404 (Masterswitch).

  • Competing interests JSS and DA received honoraria for consulting and/or speaking engagements from Roche.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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