Background/Purpose:

AA amyloidosis is the long-term complication of various chronic inflammatory diseases avoidable by the treatment of the underlying disease but with no established treatment once diagnosed. Recently there are few reports pointing out that tocilizumab (TCZ) may be effective in controlling  AA amyloidosis.

We aim to demonstrate our data on the effect of TCZ in patients with AA amyloidosis secondary to FMF.

Methods:

The follow-up data of FMF patients with histologically proven AA amyloidosis, treated with TCZ (8 mg/kg/mo) is evaluated by assessing the changes in creatinine, creatine clearance, 24-hour urine protein, erythrocyte sedimentation rate (ESR)  and C-reactive protein (CRP)  values measured before and throughout the treatment period. Adverse effects of the treatment were closely monitored.

Results:

TCZ was given to 13 patients with AA amyloidosis secondary to FMF who were also on Colchicine (2.28 ± 0.48 mg/day). Two patients had coexisting ankylosing  spondylitis, and one each had systemic lupus erythematosus and Crohn’s disease. The mean age was 37.46±9.96 years, the mean disease duration of FMF was 24.15±7.65 and of amyloidosis was 5.52±4.98. The  mean follow-up period on TCZ treatment was 12.92 ± 8.44 months. The mean creatinine levels decreased from 1.23±0.89 mg/dl to 1.07 ± 0.59 mg/dl (p <0.001), mean creatine clearance increased from 97.66±54.35 ml/min to 108.46±64.17 ml/min (p <0.001). Renal function was impaired in 4 patients which improved significantly on TCZ therapy (creatinine from a mean of 2.33±0.76 mg/dl to 1.77±0.47 mg/dl, p=0.005; creatinin clearence from a mean of 37.52±4.51ml/min to 50.82±9.84ml/min, p<0.001). The median of 24-hour urinary protein excretion for the whole group was reduced from 3038.5 mg/dl (IQR 1771-6539) to 1710 mg/d (IQR 634-4953) (p=0.007). The mean level of CRP was reduced from 22.36±20.83 mg/dl to 5.71±5.98 mg/dl (p=0.002) as the mean ESR from 52.42±33.27 mm/h to 38.30±37.50 mm/h (p=0.003).

Twelve of the patients did not experience any FMF attack under TCZ treatment. TCZ was terminated in the patient with concommitant diagnosis of SLE and APLS who had ischemic chest pain after the 12th dose, and in another patient because of an increase in the frequency of attacks associated with erysipelas-like erythema and no decrease in proteinuria. Treatment was also stopped in two other patients; one who was an illicit user of synthetic cannabinoid who developed high blood pressure 5 days after a single infusion and the other who experienced diplopia after the 6th dose. Both of these patients’ creatinine increased after termination of the therapy  (from1,43mg/dl to 2.85mg/dl;from0.8mg/dlto 3.85mg/dl, respectively) leading them to the end stage renal disease. None of the patients developed infusion reactions.

Conclusion:

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 serious side effects. Further studies are warrented to test the efficacy and safety of TCZ in AA amyloidosis secondary to FMF as well as other inflammatory conditions.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-is-effective-in-the-treatment-of-aa-amyloidosis-secondary-to-familial-mediterranean-fever/