The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6 receptor antibody tocilizumab

Abstract

Objective. SSc is an autoimmune disease characterized by fibrosis of the skin and internal organs. Although the aetiology remains uncertain, many reports have suggested that IL-6 is involved in SSc pathogenesis. Tocilizumab, an anti-IL-6 receptor antibody, is an anti-arthritis medicine that works through the blockade of IL-6 functions. To examine the effect of tocilizumab on SSc, we administered tocilizumab to two SSc patients.Methods. Two dcSSc patients were administered tocilizumab at 8 mg/kg once a month for 6 months. One patient had pulmonary fibrosis assessed by CT and spirometry, and the other had chronic renal failure caused by scleroderma renal crisis. Their skin condition was monitored with a Vesmeter and the modified Rodnan total skin score (mRTSS). Skin biopsies were obtained before and after the tocilizumab treatment to investigate the histological changes.Results. After tocilizumab treatment, both patients showed softening of the skin with reductions of 50.7 and 55.7% in the total z-score of Vesmeter hardness and 51.9 and 23.0% in the mRTSS, respectively. Histological examination showed thinning of the collagen fibre bundles in the dermis. The creatinine clearance in the patient with chronic renal failure improved from 38 to 55 ml/min. However, the fibrotic changes in the lung in the other patient remained unchanged.Conclusions. In the two cases of SSc that we report here, softening of the skin was observed during the treatment with tocilizumab.

Anti‐interleukin‐6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases

“…Two SSc patients who were resistant to conventional treatment regimens were administered tocilizumab at 8 mg/kg every 4 weeks. After the treatment, both patients showed softening of the skin with reductions of 50.7% and 55.7% in the total z-score of Vesmeter, a device for measuring the physical properties of the skin [114], and of 51.9% and 23% in the modified Rodnan total skin score [115]. Histological examination showed thinning of the collagen fiber bundles in the dermis.…”

“…RA (in more than 90 countries worldwide) [36][37][38][39][40][41][42] Castleman's disease (in Japan) [52,53] Systemic and polyarticular JIA (in Japan) [57][58][59] Candidate diseases for tocilizumab therapy: Systemic autoimmune diseases SLE [130] Systemic sclerosis [115] Giant cell arteritis and Takayasu arteritis [90,91] Polymyositis Organ specific autoimmune diseases Crohn's disease [73] Relapsing polychondritis [108] Multiple sclerosis, neuromyelitis optica Acquired hemophilia A [149] Chronic inflammatory diseases Adult-onset Still's disease [61][62][63][64][65][66][67][68] Reactive AA amyloidosis [48][49][50][51] Polymyalgia rheumatica [80,91] RS3PE [85] Spondyloarthritides [100,[102][103][104][105] Behcet's disease Uveitis GVHD [150] Autoinflammatory diseases (TRAPS) [152] Tocilizumab has been approved as a biological drug for the treatment of RA, Castleman's disease and juvenile idiopathic arthritis, and is expected to be applicable to various other autoimmune and inflammatory diseases. Abbreviations: RA, rheumatoid arthritis; JIA, juvenile idiopathic arthritis; SLE, systemic lupus erythematosus; RS3PE, remitting seronegative, symmetrical synovitis with pitti...…”

Targeting Interleukin-6 in Rheumatoid Arthritis

“…There are also case reports in regards to the use of tocilizumab in other auto-immune conditions such as giant cell arteritis [30,31], adult onset Still's disease [32] , systemic lupus erythematosus [33], ANCA-associated vasculitis [34], Behcet's disease [35,36], systemic sclerosis [37] and polymyositis [38]. These reports showed that tocilizumab was the salvage therapy used after disease resistance to various former drugs.…”

A vitamin D analog inhibits Th2 cytokine- and TGFβ -induced periostin production in fibroblasts: a potential role for vitamin D in skin sclerosis

“…These histological findings are very similar with previous findings in scleroderma patients treated with tocilizumab. 26 These patients showed softening of the skin with reductions of Vesmeter hardness, and similar histological changes. 26 Thickness of the collagen fiber bundles but not dermal thickness may be important in skin softening in scleroderma.…”