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Highlights from

American College of Rheumatology

annual meeting 2018

Chicago, Illinois 19-24 October 2018

Tocilizumab for the treatment of systemic sclerosis: efficacy and safety results from phase III trial focuSSced

Take-home messages
  • The primary endpoint was not met in focuSSced; however, clinically meaningful and consistent differences in FVC were shown in two randomised, controlled trials (focuSSced and the phase II trial faSScinate)
  • Time to treatment failure is supportive of a clinical benefit of tocilizumab in systemic sclerosis
  • No new safety signals were identified
“The primary endpoint was not met, largely because of an unexpected improvement in the placebo group.”

Professor Dinesh Khanna Professor of Rheumatology, University of Michigan, Ann Arbor, US.

Results from the phase III clinical trial focuSSced, presented at the recent 2018 American College of Rheumatology/ Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting, showed that at week 48, the primary endpoint (change in modified Rodnan skin score (mRSS)) was not met, but improved numerically (placebo, -4.41; tocilizumab, -6.14; adjusted difference in least squares mean, -1.73 (95% confidence interval (CI) -3.78 to 0.32); p=0.098).

FocuSSced is a randomised, double-blind, placebo-controlled phase III trial of tocilizumab in patients with active systemic sclerosis (SSc) (NCT02453256). Patients with SSc (N=210) were randomly assigned 1:1 to receive weekly double-blind injections of subcutaneous tocilizumab 162 mg or placebo for 48 weeks.

All patients met the ACR/EULAR criteria for active SSc, were less than 60 months from first non-Raynaud’s symptom and had no other rheumatic autoimmune disease. Other background immunomodulatory therapies were not allowed.

Professor Dinesh Khanna, Professor of Rheumatology, University of Michigan, Ann Arbor, US, who presented the results, explained, “The primary endpoint was not met... largely because of the unexpected improvement in the placebo group, which was different to what we found in our large phase II trial [faSScinate].”

Key secondary endpoints were change from baseline in percent predicted forced vital capacity (FVC) at week 48 and time to treatment failure (time from first study treatment to first occurrence of death, decline in FVC >10%, increase in mRSS >20% and mRSS ≥5, or occurrence of predefined SSc-related complications).

Secondary endpoints focusing on FVC were clinically meaningful: the cumulative distribution of change from baseline to week 48 in percent predicted FVC favoured tocilizumab over placebo (median interquartile range): placebo, -3.9 (-7.2 to 0.6) versus tocilizumab, -0.6 (-5.3 to 3.9); van Elteren p=0.0015). The difference in mean change from baseline in FVC at week 48 was 167 mL (95% CI 83 to 250) in favour of tocilizumab.

Professor Khanna noted, “The proportion of patients with an FVC decline of more than 10%, a measure of huge mortality and morbidity [in SSc], was lower with tocilizumab treatment than placebo.”

The hazard ratio (95% CI) for the time to treatment failure endpoint was 0.63 (0.37 to 1.06) in favour of tocilizumab (Cox proportional hazards model; p=0.082).

Mean change from baseline in patient- and clinician-reported outcomes (health assessment questionnaire disability index (HAQ-DI), patient visual analogue scale (VAS) and clinician VAS did not show any significant treatment effects. Safety was consistent with known complications of SSc and with the safety profile of tocilizumab: serious adverse events were reported by 17% of placebo patients and 13% of tocilizumab patients; serious infections were reported by 7% and 2% of patients, respectively.

SSc is a rare autoimmune connective tissue disease characterised by microvascular damage and fibrosis of the skin and internal organs. It has the highest morbidity and mortality of all the rheumatic diseases, and there are no approved disease-modifying treatments available - treatment is currently guided towards alleviating organ complications.

Based on Khanna D, Lin C J F et al. Efficacy and safety of tocilizumab for the treatment of systemic sclerosis: results from a phase 3 randomized controlled trial (abstract 898). Presented on Sunday 21 October 2018.

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Article image: © Kondor83

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