Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)

Abstract

ObjectivesAssess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.MethodsPatients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96.ResultsOverall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was –3.1 (6.3 (–5.4 to –0.9)) for placebo and –5.6 (9.1 (–8.9 to–2.4)) for tocilizumab at week 48 and –9.4 (5.6 (–8.9 to –2.4)) for placebo-tocilizumab and –9.1 (8.7 (–12.5 to –5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period.ConclusionsSkin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab.Trial registration numberNCT01532869; Results.

Treatment Algorithms for Systemic Sclerosis According to Experts

“…The use of rituximab as a rescue therapy is also increasing, with some observational data supporting its effectiveness in this context . Tocilizumab was only occasionally suggested, and this could be due to results of a phase III trial not yet being available along with a lack of experience and access currently in routine practice . The fourth line of treatment may include referral for ongoing clinical trials and HSCT for selected patients .…”

TGF-β pathway activation by idiopathic pulmonary fibrosis (IPF) fibroblast derived soluble factors is mediated by IL-6 trans-signaling

“…This drug was also implicated in other inflammatory conditions that involve a fibrotic phenotype, such as SS [17]. Results from the phase II randomized controlled trial (faSScinate) of SS patients showed forced vital capacity (FVC) stabilization within the TCZ receiving SS patients in comparison to placebo controls [22], as well as in placebo-treated patients who later transitioned to TCZ in the open label period [23].…”

Rapid alteration of serum interleukin‐6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis‐associated interstitial lung disease

“…By contrast, the immune cell activation and fibrosis were significantly suppressed in IL‐6R knockout mice. In fact, tocilizumab, an anti‐IL‐6R antibody that inhibits the binding of IL‐6 and IL‐6R, suppressed the development of SSc‐ILD in addition to skin sclerosis amelioration . Collectively, IL‐6 is thought to be important for the progression of fibrosis in SSc‐ILD.…”

“…Binding of IL‐6 to IL‐6R forms a complex with signal‐transducing receptor subunit gp130, resulting in the activation of various immune cells . Through these functions, IL‐6 plays crucial roles in the pathogenesis of several autoimmune diseases including SSc . IL‐6 expression is increased in the serum and skin of patients with SSc, and high serum IL‐6 levels are associated with the severity of skin sclerosis and ILD as well as reduced survival .…”