BackgroundThere 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.MethodsFMF 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.ResultsTCZ 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.ConclusıonTocilizumab 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.

Background AA amyloidosis is the major long-term complication of various chronic inflammatory diseases like rheumatoid arthritis, ankylosing spondylitis, FMF and other autoinflammatory syndromes. Treatment of the underlying disease decreases the frequency of this complication however if it develops there is no established treatment of AA amyloidosis. Recently there are few reports pointing out that tocilizumab, an anti IL-6 agent may be effective in controlling AA amyloidosis resistant to conventional treatments. Objectives We aim to demonstrate our data on the effect of tocilizumab (TCZ) in patients with AA amyloidosis secondary to FMF. Methods The follow-up data of FMF patients with histologically proven AA amyloidosis, treated with Tocilizumab (8 mg/kg – on a monthly basis) is evaluated by assessing the changes observed in creatinine, creatine clearance, the amont of 24-hour urine protein, erythrocyte sedimentation rate and C-reactive protein values measured before and throughout the treatment period. Adverse and side effects of the treatment were closely monitored. Results TCZ was given to 10 patients (6 female, 4 male) with AA amyloidosis secondary to FMF. All of the patients were on Colchicine (2.5 mg ±1 mg/day). Two patients had coexisting Ankylosing Spondylitis, one had Systemic Lupus Erythematosus and one other had Crohn's disease. The mean age was 38.5±8.5 years, while the mean disease duration of FMF was 26.1±5.5 years and of amyloidosis was 5.1±5.6 years. The mean follow-up period on TCZ treatment was 7.2±2.2 months (4-10 months). The mean creatinine level decreased from 1,34±0,97 mg/dl to 1,12±0,69 mg/dl (p=0.002) and the mean creatine clearance increased from 97,24±53,76 ml/min to 110, 30±62,42 ml/min (p<0.001). Renal function was impaired in 3 of the 10 patients which improved significantly on TCZ therapy (serum creatinine from a mean of 2.64±0,57 to 2.01±0,40mg/dl, p=0.015; creatinin clearence from a mean of 36.2±4,51 to 45.3±5,55 ml/min, p=0,005). The median of 24-hour urinary protein excretion for the whole group was reduced from 3019,25 mg/dl (IQR 1683,70-7513,50) to 1663,50 mg/d (IQR 402,18-2943,90) (p value=0.007). A significant decrease in acute phase reactants was also recorded. The mean level of C-reactive protein was reduced from 18,88±18,90 mg/dl to 6,73±8,57 mg/dl (p=0,012) as the mean erythrocyte sedimentation rate was reduced from 42,10±28,08 mm/h to 19,55±20,92 mm/h (p=0,001). Eight of the patients did not experience any FMF attack under TCZ treatment. However in one patient TCZ was switched to canakinumab because of an increase in the frequency of attacks associated with erysipelas-like erythema and no decrease in proteinuria. One other patient with FMF and AS had 2 attacks of acute sacroiliitis during the follow-up. No serious adverse event was observed related to TCZ treatment. Conclusions TCZ improves the acute phase response and the renal function impaired by amyloidosis secondary to FMF. Among this patient group TCZ treatment is well tolerated and not associated with s...