Excellent therapeutic effect of tocilizumab on intestinal amyloid a deposition secondary to active rheumatoid arthritis

Abstract

A 64-year-old woman suffering from progressive amyloid A (AA) amyloidosis of the gastrointestinal (GI) tract, associated with active rheumatoid arthritis, was transferred to our hospital due to hypovolemic shock. Although intensive care, including treatment with prednisolone and methotrexate, improved the hypovolemic shock, paralytic ileus became dominant instead of the marked diarrhea, suggesting the terminal stage of AA amyloidosis of the GI tract. Thus, we administered tocilizumab, a humanized anti-interleukin 6 receptor antibody (8 mg/kg, repeated every 4 weeks). Two weeks after the first injection of tocilizumab, serum AA rapidly returned to their normal ranges in accordance with the amelioration of paralytic ileus and systemic joint pain. Surprisingly, after three courses of tocilizumab treatment, colon biopsy revealed no amyloid deposition. Tocilizumab is a promising agent to treat secondary AA amyloidosis by strongly suppressing serum AA levels.

Therapeutic Effects of Lenalidomide on Hemorrhagic Intestinal Myeloma-associated AL Amyloidosis

“…In fact, we previously observed rapid disappearance of intestinal AA amyloid following the administration of tocilizumab in a patient with severe rheumatoid arthritis (17). Although we did not histologically confirmed a reduction in intestinal amyloidosis in the present case, marked endoscopic improvement in the submucosal tumoral lesions strongly suggests decreased intestinal amyloid deposition.…”

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

“…Three case studies of reactive AA amyloidosis, complicated by RA reported the ameliorative clinical effect of tocilizumab on gastrointestinal symptoms due to intestinal amyloidosis [49][50][51]. Surprisingly, amyloid A fibril deposits were found to have disappeared in two cases after three injections of tocilizumab.…”

“…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...…”

Tocilizumab for the Treatment of AA Amyloidosis

“…Surprisingly, three months after the tocilizumab treatment amyloid A protein deposits had completely disappeared. Subsequently, two other cases of AA amyloidosis associated with RA also showed the ameliorative clinical effect of tocilizumab on gastrointestinal symptoms due to intestinal amyloidosis (Sato et al, 2009;Inoue et al, 2010) and in one of the two cases amyloid A fibril deposits were found to have disappeared after three courses of tocilizumab treatment. Moreover, Kishida et al reported observing the clinical ameliorative effect of tocilizumab on a patient with adult-onset Still's disease complicated by AA amyloidosis as well as marked regression of amyloid A protein in duodenal mucosa and submucosa after tocilizumab treatment (Kishida et al, 2010).…”