Real life data of anti interleukin-1 treatmant in patients with familial mediterranean fever related amiloidosis followed in our center

Aim: Familial Mediterranean Fever is the most common periodic fever syndrome in the world. Especially it's affecting the ethnic groups originating from Mediterranean basin but our country has the highest incidance and prevalence all over the world. Colchicine is used for treatment of FMF since 1972. Patients who didn't respond well to colchicine treatment for many reason; now have a second option called anti IL-1 treatment. There are many trials and case reports on anti IL-1 use in FMF that demonstrates their efficacy and safety. The objective of this study is to demostrate efficacy of anti IL-1 therapy in FMF patients with AA amyloidosis. Materials and methods: In our study, we evaluated all data since 2010 from database of Ankara city hospital rheumatology department, Ankara Numune research hospital and Ankara Atatürk research hospital rheumatology department and we found all patients who use anti IL-1 therapy for FMF asosiated AA amyloidosis. All of the patients were older than 18; diagnosed as FMF according to Tel Hasomer criteria and diagnosed AA amyloidosis associated FMF, too. Also they have used anti IL-1 therapy minimum six months regularly. We have determined patients' attack frequency, sedimantation levels, fibrinogen levels, C reactive protein levels, proteinüria levels and renal function parameters before anti IL-1 therapy and after six months regular therapy and at the last visit. We had phone calls with patients about their therapy, anti IL-1's affect on FMF attack frequency, disease severity, side affects and patients' compliance to anti IL-1 therapy. The obtained data were uploaded to the SPSS database and analyzed statistically. Results: A total of 26 patients were reached in our study. Women were 34.6% of these patients and 65.4% were men. The mean age of the patients was 41 ± 9.5 (24-65). All patients were using colchicine (min:1.5mg/hf-max:2mg/day) at the maximum dose they could tolerate and anti IL-1 treatment was added on this treatment. Anakinra was started for the first time in all 26 patients, and seven patients later switched to kanakinumab treatment. The attack frequencies of the patients in the last six months were determined. While the attack frequency before anti IL-1 treatment was 5 ± 3.3 (min: 1-max: 12), after six months of treatment the attack frequency decreased to 0.8 ± 1.1 (min: 0-max: 3) and this value was statistically significant (p <0.002). The decrease in ESR, CRP, and fibrinogen levels was also statistically significant (p <0.001). For ESR, the value before anti IL-1 treatment was 55 ± 25.4 54 (min: 7-max: 112) mm / hr, but after six months of treatment, it decreased to 24 ± 22.3 14 (min: 3-max: 76) mm / hr. While the CRP value before anti IL-1 treatment was 31.4 ± 36.7 19 (min: 1-max: 159) mg /l, it was found to be 7.9 ± 14 3 (min: 0.3-max: 54) mg /l after six months of treatment. In fibrinogen, the initial mean value was 578 ± 193 575 (min: 286-max: 900) mg / l, and after six months of treatment it regressed to 379 ± 173 342 (min: 191-max: 884) mg / l. In addition, the 24-hour urinary proteinuria levels of the patients decreased from 5 454 ± 7 396 2 075 (min: 229-max: 30 211) mg / day before the anti IL-1 treatment to 2 703 ± 3 179 1 175 (min: 100-max: 10 759) after six months of treatment, and this value was also statistically significant (p <0.01). The decrease in the white blood cell levels (p = 0.007), platelet levels (p = 0.002) and neutrophil levels (p = 0.02) of our patients were also statistically significant before anti IL-1 treatment and six months after treatment. Impaired renal function tests were observed under anti IL-1 treatment. While pre-treatment creatinine level was 1.6 ± 0.97 1.3 (min: 0.52-max: 4.11), it increased to 1.87 ± 1.24 1.5 (min: 0.5-max: 4.41) at six months after treatment (p = 0.007). Consistent with this data, a decrease in GFR was also detected (p <0.05). At the end of a mean follow-up period of 44 months, one patient died of an unrelated cause of amyloidosis, kidney transplantation was performed in five patients, and hemodialysis was initiated in nine patients due to end-stage renal disease. While there was no significant change in creatinine and GFR levels in the remaining 11 patients, the decrease in urine protein continued (p <0.05). At the end of the follow-up period, 50% of the patients had local reaction, 11% allergic rash, 23% leukopenia and 11% increase in the frequency of infection. There was an increase in the frequency of infection in three patients. Two of them who experienced an increase in the frequency of infection were treated in the intensive care unit. Bone marrow aspiration biopsy was performed in two of the patients who developed leukopenia and malignant transformation was not found. Conclusion: Anti IL-1 therapy appears to be effective on clinical, acute phase response and proteinuria level in FMF patients with amyloidosis. In some patients, it may delay the progression to chronic kidney disease by providing regression in proteinuria. However, in some patients, it was observed that amyloidosis accumulation continued and many patients with amyloidosis needed renal replacement therapy in the long term. Key words: Familial mediterranean fever, Amyloidosis, Anti IL-1 treatment, Anakinra, Canakinumab