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 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.
Disclosure of Interest : None declared