The experience of canakinumab in renal amyloidosis secondary to Familial Mediterranean fever

Sözeri, Betül; Gülez, Nesrin; Ergin, Malik; Serdaroğlu, Erkin

doi:10.1186/s40348-016-0058-2

Cited by 21 publications

(9 citation statements)

References 28 publications

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“…It even progressed in two patients, showing renal tissue damage after improving proteinuria with anti-IL-1 treatment in AID-related amyloidosis (22). Sözeri et al reported that in a patient with FMF-related renal amyloidosis and nephrotic range proteinuria, 26-month canakinumab treatment resulted in improved inflammatory parameters and decreased proteinuria (23). Colchicine and biologic agents aiming at reduced SAA protein in FMF could facilitate the regression of amyloid accumulation (24).…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Canakinumab Treatment in Colchicine Resistant Familial Mediterranean Fever Cases

et al. 2021

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Anti-interleukin 1 agents are used successfully in colchicine-resistant or intolerant Familial Mediterranean Fever (FMF) patients. Sixty-five patients with FMF who received canakinumab treatment for at least 6 months due to colchicine resistance or intolerance between 2016 and 2020 in our department were retrospectively analyzed. Canakinumab treatment was given subcutaneously every 4 weeks. After completing monthly canakinumab therapy over 12 months, in patients with complete remission, the dosing interval was extended to every 1.5 months for 6 months, then every 2 months for 6 months, and finally every 3 months for a year. In patients without disease activation, canakinumab treatment was discontinued at the end of 3 years and followed up with colchicine treatment. Patients who had a flare switched to the previous dosing interval. In patients with renal amyloidosis, monthly canakinumab treatment was continued without extending the dose intervals. The mean duration of canakinumab use in our patients was 31.4 ± 10.57 months (6–52 months). The mean age at onset of symptoms was 4.65 ± 3.84 (range, 1–18) years, and the mean age at diagnosis was 5.59 ± 3.9 (range, 4–19) years. Complete remission was achieved in 57 (87.6%) and partial remission in seven (10.7%) patients. One patient was unresponsive to treatment. Canakinumab treatment was discontinued in three patients with complete remission and one patient with drug resistance. Erythrocyte sedimentation rate (ESR) (51.85 ± 15.7 vs. 27.80 ± 13.73 mm/h) and C-reactive protein (CRP) [26 (3-73) vs. 5 (1–48) mg/L] values were compared before and after canakinumab treatment in attack-free periods, a significant decrease was found after canakinumab treatment (p < 0.001, p < 0.001, respectively). Bodyweight Z-scores (respectively −0.80 ± 0.86 vs. −0.49 ± 0.92) were compared, similarly, a statistically significant increase after canakinumab treatment (p < 0.001), but no significant increase in height Z scores (−1.00 ± 0.88 vs. −0.96 ± 0.94) (p = 0.445) was detected. Four patients had FMF-related renal amyloidosis. The decrease in proteinuria with canakinumab treatment was not statistically significant (p = 0.068). Cervical lymphadenitis developed in one and local reactions in two patients. No severe adverse effects requiring discontinuation of canakinumab treatment were observed. Our study showed that canakinumab treatment was highly effective, well-tolerated in pediatric FMF patients, and controlled extension of the canakinumab dose interval was safe.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Canakinumab Treatment in Colchicine Resistant Familial Mediterranean Fever Cases

et al. 2021

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“…Currently, IL-1 inhibitors, including canakinumab, have been shown to be effective in treating crFMF [32,33], but in some cases, they are not effective enough or cannot be used due to adverse events. IL-1 inhibitors have also been shown to be effective against amyloidosis [34,35]. It has been proposed that IL-6 inhibitors may have a higher potential to normalize SAA than other biologic agents [36] and IL-6 inhibitors have been suggested to be useful in preventing the progression of amyloidosis and improving amyloid deposition [21,37].…”

Section: Discussionmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled Phase III Trial On The Efficacy and Safety of Tocilizumab in Patients With Colchicine-Resistant or -Intolerant Familial Mediterranean Fever

Koga

Sato

Hagimori

et al. 2021

Preprint

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Objective To evaluate the efficacy and safety of tocilizumab (TCZ), an interleukin 6 receptor monoclonal antibody, in patients with familial Mediterranean fever (FMF). Methods We performed a double-blind, randomized, parallel-group trial, followed by an open-label extension trial, in patients with colchicine-resistant or -intolerant FMF (crFMF). Patients were randomly assigned (1:1) to receive TCZ (162 mg every week) or placebo, administered subcutaneously, for 24 weeks. Rescue treatment was allowed if the rescue criteria were met. The primary endpoint was the number of fever attacks over the 24 weeks of treatment. Secondary endpoints included the frequency of accompanying symptoms during attacks, serum CRP and SAA values, and adverse events (AEs). The open-label extension study evaluated the long-term safety and efficacy of TCZ in patients who had completed the preceding study. Results We randomly assigned 23 patients to either TCZ (n = 11) or placebo (n = 12). The TCZ–placebo rate ratios were 0.691 (95% confidence intervals (CI), 0.189–2.531; P = 0.577) for the fever attacks, based on the group rates per week. The recurrence of attacks was significantly lower in the TCZ group (hazard ratio = 0.457; 95% CI, 0.240–0.869). Fever attacks, accompanying symptoms, serum CRP and SAA values were controlled in most of the patients who received long-term TCZ. In these trials, the numbers and severity of AEs did not differ between groups. Conclusion Although a primary endpoint was not met in the preceding trial, long-term administration of TCZ showed stable efficacy and safety for patients with crFMF.

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“…The older patient, the father, affected by renal insufficiency (serum creatinine 2 mg/dl, eGFR= 37 ml/min) and nephrotic proteinuria (7 g/daily), started therapy with canakinumab (Sozeri et al, 2016;van der Hilst et al, 2016) on September 2011, at the dose of 150 mg subcutaneously every 60 days.…”

Section: Case Reportmentioning

confidence: 99%

“…Later, graft function continued to improve until serum creatinine levels of 1.6 mg/dl (eGFR=46 ml/min, by CKD-EPI formula) 45 days after kidney transplantation. The therapy with monoclonal anti-IL-1b antibody (canakinumab 150 mg subcutaneously every 60 days) (Scarpioni et al, 2015;Sozeri et al, 2016;van der Hilst et al, 2016) has been continued at the same dosage after renal transplantation in order to avoid the amyloid deposition, without relapsing of the underlying disease.…”

Section: Case Reportmentioning

confidence: 99%

NLRP3 Inflammasome Activation in Renal Injury: Long-Term Effectiveness and Safety of Blocking the IL-1 System in a Kidney Transplanted Patient Affected by AA Amyloidosis Secondary to Cryopyrin-Associated Periodic Syndromes (CAPS)

Melfa¹,

Rocca²,

Comai³

et al. 2021

FMCR

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NLRP3 inflammasome activation is recognized to play a key role in the pathogenesis of several chronic diseases such as chronic tubulointerstitial diseases, glomerulonephritis and calcium oxalate crystal nephropathy. Genetic variants of NLPR3 are likely associated to pro-inflammatory/autoimmune disorders, by the altered self-regulation of inflammasome with overproduction of inflammatory cytokines. Recently experimental and human studies have focused on the interest in both acute and chronic renal diseases. Inhibition of the Interleukin-1 (IL-1) system has become an attractive potential therapeutic target in a variety of renal disorders, including IgA nephropathy, ischemic reperfusion injury, after unilateral ureteral obstruction, rhabdomyolisys-induced Acute Kidney Injury (AKI), contrast-induced AKI, crystalline nephropathy, and recently also in diabetic nephropathy.NLRP3 activation in kidney diseases magnify inflammation and subsequent fibrosis, and this effect is abrogated by genetic or pharmacologic deletion of NLRP3. Inflammasome-dependent NLRP3 mediates the progression of kidney diseases by rapidly increasing the inflammatory response in immune cells as demonstrated also in hereditary autoimmune syndromes, like CAPS. We describe the renal involvement in one patient affected by Muckle-Wells syndrome (MWS), biopsy-proven reactive AA amyloidosis and proteinuric renal failure, by focusing the interest above all on the efficacy and safety profile of therapy with anti-IL1 antibody on a clinical continuum from the reduced renal function to the kidney transplant.

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The experience of canakinumab in renal amyloidosis secondary to Familial Mediterranean fever

Cited by 21 publications

References 28 publications

Effectiveness of Canakinumab Treatment in Colchicine Resistant Familial Mediterranean Fever Cases

Effectiveness of Canakinumab Treatment in Colchicine Resistant Familial Mediterranean Fever Cases

A Randomized, Double-Blind, Placebo-Controlled Phase III Trial On The Efficacy and Safety of Tocilizumab in Patients With Colchicine-Resistant or -Intolerant Familial Mediterranean Fever

NLRP3 Inflammasome Activation in Renal Injury: Long-Term Effectiveness and Safety of Blocking the IL-1 System in a Kidney Transplanted Patient Affected by AA Amyloidosis Secondary to Cryopyrin-Associated Periodic Syndromes (CAPS)

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