The Preferential Use of Anakinra in Various Settings of FMF: A Review Applied to an Updated Treatment-Related Perspective of the Disease

Giat, Eitan; Ben-Zvi, Ilan; Lidar, Merav; Livneh, Avi

doi:10.3390/ijms23073956

Cited by 7 publications

(4 citation statements)

References 165 publications

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“…Colchicine is an alkaloid that inhibits many cellular functions, including microtubule assembly, cell adhesion, and inflammasome activation (13,14). It is mainly metabolized in the liver via demethylation by the cytochrome P450 system (15).…”

Section: Discussionmentioning

confidence: 99%

Does switching from coated colchicine to compressed colchicine improves treatment response in patients with familial Mediterranean fever?

Öner,

Çelikel,

Tekin

et al. 2023

Croat Med J

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AimTo evaluate the treatment response to compressed colchicine tablets in familial Mediterranean fever (FMF) patients with resistance or intolerance to coated colchicine. The secondary aim was to determine the demographic and clinical characteristics of responders to compressed colchicine. MethodsWe retrospectively reviewed the medical records of 1574 pediatric patients with FMF treated at Ankara Bilkent City Hospital. Sixty-one patients did not respond to coated colchicine and were switched to compressed colchicine. In these patients, the number of attacks and the International Severity Score for FMF (ISSF) during the 6 months before and 3, 6, 9, 12, and 24 months after switching from coated colchicine to compressed colchicine were recorded. ResultsTwelve of 61 patients (19.7%) who were switched to compressed colchicine due to intolerance responded to treatment. Of the 49/61 patients (80.3%) who were switched due to uncontrolled attacks and persistent subclinical inflammation, 25 responded to treatment. The frequency of attacks and ISSF decreased after switching. At the end of the two-year follow-up, 42 patients responded to compressed colchicine, and 19 patients received compressed colchicine plus interleukin-1-targeting drugs.Conclusions Compressed colchicine was shown to be a useful treatment option before initiating biological agents in non-responders to coated colchicine, especially those with side effects.

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Section: Discussionmentioning

confidence: 99%

Does switching from coated colchicine to compressed colchicine improves treatment response in patients with familial Mediterranean fever?

Öner,

Çelikel,

Tekin

et al. 2023

Croat Med J

View full text Add to dashboard Cite

show abstract

“…Colchicine is an alkaloid which inhibits many cellular functions, including microtubule assembly, cell adhesion, and in ammasome activation [13,14]. Colchicine is mainly metabolized in the liver via demethylation by the cytochrome P450 system [15].…”

Section: Discussionmentioning

confidence: 99%

Does Switching Colchicine Preparations Have a Role in The Treatment of Familial Mediterranean Fever?

Öner

Çelikel

Tekin

et al. 2022

Preprint

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Objective: The aim of this study was to evaluate the treatment response of compressed colchicine tablets in familial Mediterranean fever (FMF) patients with resistance or intolerance to coated colchicine. Another objective was to determine the demographic and clinical characteristics of the group that responded to compressed colchicine preparations. Methods: In this retrospective study, the files of 1574 patients with FMF in our center were reviewed. Sixty-one patients who did not respond to coated colchicine and were switched to compressed colchicine treatment were evaluated. The number of attacks and the International Severity Score for FMF (ISSF) during the 6 months before and 3, 6, 9, 12, and 24 months after switching from coated colchicine to compressed colchicine were recorded. Results: Of the 61 patients, 36 (59%) were boys, and 25 (41%) were girls. The mean age of symptom onset was 34±22 months. The mean age at diagnosis was 8.4±5.1 years. The mean age at the time of switching from coated colchicine to compressed colchicine was 11.8±3.5 years. Among 61 patients whose treatments were switched to compressed colchicine, 12 had intolerance, while 49 had uncontrolled attacks and persistent subclinical inflammation. The problems of 12 patients who were switched to compressed colchicine due to intolerance were resolved. Response to compressed colchicine was observed in 25/49 patients with uncontrolled attacks and persistent subclinical inflammation. The frequency of attacks decreased significantly at the 3rd and 6th months after switching from coated colchicine to compressed colchicine (p<0.05). The mean ISSF score of the patients in the last 3 months while receiving coated colchicine was 5.4±2.3. The mean ISSF scores of the patients at the 3rd and 6th months after switching to compressed colchicine were 3.2±2.1 and 2.6±1.7, respectively. Twenty-four of the 49 patients did not respond to compressed colchicine. Anakinra was added to the treatments of 14 of the 24 patients, and canakinumab was added to the treatments of 10. The frequency of attacks and ISSF scores of the patients who did not respond to compressed colchicine significantly decreased after the addition of IL-1-targeting drugs to their treatments. At the end of the two-year follow-up, 42 patients were tolerant to compressed colchicine, and 19 patients (4 anakinra, 15 canakinumab) were on compressed colchicine plus IL-1-targeting drugs. Conclusions: Compressed colchicine was shown to be a useful treatment option before initiating biological agents in patients who were unresponsive to coated colchicine, especially those with side effects.

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“…Although the nadir of the arterial pressure response to Ant occurs ≈15 minutes following administration, pressure gradually returns toward baseline over the course of an hour. Because the half-life of Ant is 4 to 6 hours and longer in situations of renal insufficiency such as the uninephrectomized DOCA-salt model, 18 this is likely due to reflex neurohormonal responses to an acute decrease in arterial pressure.…”

Section: Role Of the Il-1r In Mediating The Effects Of Ardn On Arteri...mentioning

confidence: 99%

IL-1R Mediated Activation of Renal Sensory Nerves in DOCA-Salt Hypertension

Baumann,

Van Helden,

Evans

et al. 2024

Hypertension

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BACKGROUND: Clinical trials of renal denervation for the treatment of hypertension have shown a variety of off-target improvements in conditions associated with sympathetic overactivity. This may be due to the ablation of sympathoexcitatory afferent renal nerves, which are overactive under conditions of renal inflammation. Renal IL (interleukin)-1β is elevated in the deoxycorticosterone acetate-salt model of hypertension, and its activity may be responsible for the elevation in afferent renal nerve activity and arterial pressure. METHODS: Continuous blood pressure recording of deoxycorticosterone acetate-salt mice with IL-1R (IL-1 receptor) knockout or antagonism was used individually and combined with afferent renal denervation (ARDN) to assess mechanistic overlap. Protein quantification and histological analysis of kidneys were performed to characterize renal inflammation. RESULTS: ARDN attenuated deoxycorticosterone acetate-salt hypertension (−20±2-Δmm Hg mean arterial pressure [MAP] relative to control at study end) to a similar degree as total renal denervation (−21±2-Δmm Hg MAP), IL-1R knockout (−16±4-Δmm Hg MAP), or IL-1R antagonism (−20±3-Δmm Hg MAP). The combination of ARDN with knockout (−18±2-Δmm Hg MAP) or antagonism (−19±4-Δmm Hg MAP) did not attenuate hypertension any further than ARDN alone. IL-1R antagonism was found to have an acute depressor effect (−15±3-Δmm Hg MAP, day 10) in animals with intact renal nerves but not those with ARDN. CONCLUSIONS: These findings suggest that IL-1R signaling is partially responsible for the elevated afferent renal nerve activity, which stimulates central sympathetic outflow to drive deoxycorticosterone acetate-salt hypertension.

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The Preferential Use of Anakinra in Various Settings of FMF: A Review Applied to an Updated Treatment-Related Perspective of the Disease

Cited by 7 publications

References 165 publications

Does switching from coated colchicine to compressed colchicine improves treatment response in patients with familial Mediterranean fever?

Does switching from coated colchicine to compressed colchicine improves treatment response in patients with familial Mediterranean fever?

Does Switching Colchicine Preparations Have a Role in The Treatment of Familial Mediterranean Fever?

IL-1R Mediated Activation of Renal Sensory Nerves in DOCA-Salt Hypertension

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