Tocilizumab in the treatment of twelve cases with aa amyloidosis secondary to familial mediterranean fever

Abstract

Background: There is no established treatment of AA amyloidosis, a long-term complication of various chronic inflammatory diseases associated with increased mortality, such as familial Mediterranian fever (FMF). Recently there are few reports pointing out that tocilizumab(TCZ), an anti IL-6 agent may be effective in AA amyloidosis resistant to conventional treatments. We report our data on the effect of TCZ in patients with FMF complicated with AA amyloidosis.

Methods: FMF patients with histologically proven AA amyloidosis, treated with TCZ (8 mg/kg per month) were followed monthly and the changes in creatinine, creatinine clearance, the amount of 24-hour urinary protein, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were noted throughout the treatment period. Adverse effects of the treatment were closely monitored.

Results: TCZ was given to 12 patients (6 F, 6 M) who also continued to receive colchicine (1.9 ± 0.4 mg/day). Coexisting diseases were ankylosing spondylitis(4) and Crohn's disease(1). The mean age was 35.2 ± 10.0 years and the mean follow-up on TCZ was 17.5 ± 14.7 months. The renal functions remained stable (mean creatinine from 1.1 ± 0.9 mg/dl to 1.0 ± 0.6 mg/dl), while a significant decrease in acute phase response (the mean CRP from 18.1 ± 19.5 mg/L to 5.8 ± 7.1 mg/L and ESR from 48.7 ± 31.0 mm/h to 28.7 ± 28.3 mm/h) was observed and the mean 24-hour urinary protein excretion reduced from 6537.6 ± 6526.0 mg/dl to 4745.5 ± 5462.7 mg/dl. Two patients whose renal functions were impaired prior to TCZ therapy improved significantly on this regimen. No infusion reaction was observed. None of the patients experienced any FMF attack under TCZ treatment with the exception of 2, one of whom had less frequent attacks while the other had episodes of erysipelas-like erythema. CONCLUSıON: Tocilizumab improved the acute phase response and the renal function in this group of patients and was generally well tolerated. Besides improving the renal function TCZ seemed to control the recurrence of FMF attacks too. Further studies are warrented to test the efficacy and safety of TCZ in AA amyloidosis secondary to FMF as well as other inflammatory conditions.

Keywords: AA amyloidosis; Familial Mediterranian fever; Tocilizumab.