Background/Purpose:

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 (TCZ), an anti IL-6 agent may be effective in controlling resistant 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 per month) is evaluated by assessing the changes in creatinine, creatine clearance, the amount of 24-hour urine protein, erythrocyte sedimentation rate (ESR)  and C-reactive protein (CRP)  values measured before and throughout the treatment period. Adverse and side effects of the treatment were closely monitored.

Results:

TCZ was given to 13 patients (8 female, 5male) with AA amyloidosis secondary to FMF who were also on Colchicine (2.28 mg± 0.48 mg/day). Two patients had coexisting ankylosing spondylitis, one had systemic lupus erythematosus and one other had Crohn’s disease. The mean age was 36.46±9.96 years, while the mean disease duration of FMF was 23.15±7.65 years and of amyloidosis was 4.52±4.98 years. The mean follow-up period on TCZ treatment was 8.76 ± 5.59 months. The mean creatinine levels decreased from 1.21±0.93 mg/dl to 1.05 ± 0.65 mg/dl (p  = 0.001), mean creatine clearance increased from 102.34±53.95 ml/min to 109.08±60.23 ml/min (p <0.001). Renal function was impaired in 3 of the 13 patients which improved significantly on TCZ therapy (serum creatinine from a mean of 2.64±0.57 mg/dl to 1.97±0.46 mg/dl, p=0.018; creatinin clearence from a mean of 36.2±4.51 to 45.3±5.55ml/min, p=0.005). The median of 24-hour urinary protein excretion for the whole group  was reduced from 3038.5 mg/dl (IQR 1827-7061) to 1155mg/d (IQR 802-4707) (p=0.013). A significant decrease in acute phase reactants was also recorded. The mean level of CRP was reduced from 19.43 ±18.75 mg/l to 3.87±4.8 mg/dl (p=0.004) as the mean ESR was reduced from 45.41±26.68 mm/h to 27.63 ± 29.25 mm/h (<0.001). 

Twelve of the patients did not experience any FMF attack under TCZ treatment. 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.  Increased blood pressure (220/120 mm Hg)  was noted 5 days after the single infusion in one patient who was an illicit user of synthetic cannabinoid.  TCZ was stopped in one other patient with underlying SLE and APLS  who developed ishemic chest pain after the 12th infusion.

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-tcz-in-the-treatment-of-aa-amyloidosis-in-patients-with-familial-mediterranean-fever/