Tocilizumab in Amyloidosis-Associated Kidney Disease Secondary to Inflammatory Bowel Diseases

Abstract

We read with interest the article by Sattianayagam et al. [1] about inflammatory bowel diseases (IBD) and AA amyloidosis with amyloidosis-associated kidney disease. The authors concluded that suppression of inflammatory activity may improve systemic amyloidosis prognosis and that patients undergoing renal transplantation have an excellent outcome. There is some evidence of the efficacy of the humanized anti-interleukin-6 receptor antibody tocilizumab (TCZ) on renal failure associated with AA amyloidosis improvement. TCZ has been reported to be effective in secondary AA amyloidosis related to rheumatologic diseases [2], in amyloidosis in the GI tract [3], and in renal amyloidosis [4], despite the scarcity of controlled evidence. In support of the effect of TCZ, we report the case of a 45-year-old patient with ulcerative colitis and grade III sacroileitis (HLA-B27 negative), followed in another center. After an acute flare, refractory to corticosteroids and cyclosporine, the patient underwent a proctocolectomy with an ileoanal pouch. Ten years later he was referred to our unit with elevated inflammatory markers, diarrhea, and abdominal pain. He had suffered from mild to moderate symptoms for at least the two previous years. Endoscopy revealed extensive ulceration of the pouch, jejunum, and ileum. Crohn’s disease was therefore diagnosed, and, because of persistent clinical activity, he was treated sequentially with adalimumab, infliximab, and methotrexate, without clinical response. Concurrently, the patient developed progressive chronic kidney disease with non-nephrotic range proteinuria reaching CKD stage IV (glomerular filtration rate \15 ml/min/m). After exclusion of other potential causes of renal dysfunction in IBD (5-ASA treatment, hypercalcemia renal oxalate stones), AA amyloidosis secondary to chronic inflammation related to IBD was diagnosed on the basis of amyloid A deposits in subcutaneous fat biopsy and duodenum, ileum, and colon biopsies (Congo redstained positive). Because of the clinical activity and the diagnosis of AA amyloidosis, we decided to start TCZ 8 mg/kg monthly. Tolerance of the treatment was excellent and the patient improved progressively and achieved clinical remission at week 52. At week 64, an ileoscopy, through the ileostomy, and a capsule endoscopy were performed; these showed mucosal healing was complete. In addition, renal function improved progressively and remained stable for two years (Cr 2.4 mg/dl, GFR 32 ml/min/1.73 m). Ileal biopsies performed two years after the onset of treatment showed no AA deposits. This clinical case and the literature published so far emphasize the importance of TCZ in controlling inflammatory activity in IBD and in reducing AA deposits, leading to improvement of renal function. It may therefore be considered as an alternative treatment or as bridge therapy before renal replacement therapy.