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Anakinra treatment in colchicine-resistant or colchicine-intolerant Familial Mediterranean Fever: real-world experience

Summary by Dr Catherine Grandpeix-Guyodo

First author: Tuğba Ocak

Journal: Medicina

Reference: Medicina (Kaunas). 2025 Apr 25; 61: 792


Anakinra treatment in colchicine-resistant or colchicine-intolerant Familial Mediterranean Fever: real-world experience

Introduction:

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is associated with MEFV gene mutations and is characterized by recurrent inflammatory attacks, particularly with abdominal pain. The most severe complication is AA amyloidosis. The recommended treatment is colchicine to prevent attacks and complications. In some patients, colchicine at the maximum tolerated dose is insufficient to prevent attacks, while others do not tolerate colchicine. Anti–interleukin‑1 agents are effective in cases of colchicine resistance or intolerance. This Turkish team investigated treatment with anakinra in colchicine‑resistant/intolerant FMF patients, focusing on their clinical characteristics, treatment duration, treatment response, possible extension of injection intervals, and long‑term outcomes.


Patients and methods:

This single‑center retrospective study included 68 FMF patients with colchicine resistance or intolerance who required initiation of anakinra at a dose of 100 mg/day. Colchicine resistance was defined as at least one attack per month despite the maximum tolerated daily dose of colchicine. Colchicine intolerance was defined as the inability to increase the colchicine dose because of digestive side effects.


Results:

Among these 68 patients, the median age was 40.2 years and 57.3% were women. Of the 60 patients who had undergone genetic testing, 32 patients (53%) had two pathogenic MEFV mutations, 26 (43%) were heterozygous for pathogenic mutations, and 2 had no identified mutation.


Fifteen patients had AA amyloidosis. All patients were treated with colchicine before starting anakinra, at a median dose of 2 mg/day, and 63 patients continued colchicine in parallel. Median follow‑up was 34 months.


Treatment was effective in the majority of patients, with significant reductions in the Pras score, ESR, CRP, SAA, and proteinuria when present.


In 21 patients, remission was achieved under treatment, allowing an increase in the interval between anakinra injections to every 2 days, then every 3 days. Eight of these patients were able to discontinue anakinra completely while continuing colchicine alone. Only 2 patients relapsed within the month following complete treatment withdrawal.


The main adverse events were injection‑site reactions.


Seventeen additional treatment discontinuations were reported, mostly due to insufficient response (7 patients) or adverse events (7 patients).


Four patients received anakinra during pregnancy without adverse effects in either the mother or the baby.


Six kidney‑transplant recipients were treated with anakinra, one of whom died from COVID‑19 pneumonia.


Discussion:

This study shows that treatment with anakinra in patients who are resistant or intolerant to colchicine leads to rapid and sustained improvement in clinical signs and inflammatory markers, with good tolerability. Injection intervals could be extended to every 2 or even 3 days while maintaining clinical and biological response. Proteinuria decreased in some patients, suggesting a potential benefit in those with AA amyloidosis. Treatment was also well tolerated, with no adverse effects reported in the 4 pregnant women.


In practice:

In this study of 68 Turkish adults with FMF, anakinra was rapidly effective and well tolerated in the long term in patients who were resistant or intolerant to colchicine.

 
 
 

Familial Mediterranean Fever: a single dose of anakinra to stop an acute attack

Article title: A single dose of anakinra for arresting Familial Mediterranean Fever attacks: a proof-of-concept study

First author: E. Giat

Journal: Clinical and Experimental Rheumatology

Author of the abstract: Dr Catherine Grandpeix-Guyodo


La Méditerranée

Introduction

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is characterized by recurrent febrile attacks of serositis (peritonitis, pleuritis, arthritis) and may, in the long term, be complicated by AA amyloidosis in cases of uncontrolled chronic inflammation. Colchicine is the standard long-term treatment; however, some patients experience incomplete response or intolerance, leading to the continuous use of IL-1 inhibitors (anakinra or canakinumab). Nevertheless, acute attacks may still occur despite treatment, and their management remains largely symptomatic, with limited efficacy of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs).


Patients and Methods

The objective of this prospective study was to evaluate the efficacy of a single dose of anakinra (100 mg subcutaneously) administered at the onset of an attack to interrupt its progression. The study included patients with typical FMF according to Tel Hashomer criteria, carrying one or two pathogenic MEFV mutations, treated with colchicine, and having experienced at least two serositis attacks in the previous year. Patients receiving continuous anti–IL-1 therapy were excluded, as were those with atypical attacks or chronic inflammatory states.


Patients were provided with a prefilled syringe of anakinra and received training in self-injection and early recognition of attack symptoms. The duration of treated attacks was compared with each patient’s usual attack duration.


Results

Thirty-five patients agreed to participate: five were excluded due to persistent inflammation; four experienced no attacks during the study period; two did not ultimately use anakinra during an attack; and one discontinued due to an adverse event. A total of 23 patients were analyzed, including 13 with two pathogenic MEFV mutations (considered to have “classical” FMF) and 10 with a single pathogenic MEFV mutation (considered “heterozygous” FMF).


The mean duration of treated attacks was 8.3 ± 6.8 hours, compared with 56.3 ± 16.8 hours under usual conditions. When anakinra was injected within the first 4 hours of attack onset, 85% of attacks were interrupted within 4 hours after injection. Later injections resulted in a less pronounced but still significant reduction compared with usual attack duration. Overall, 91% of treated attacks lasted less than 24 hours. Only one adverse event was reported (local injection-site reaction), highlighting the good tolerability of this strategy.


Six patients continued to use self-purchased anakinra to treat 43 additional attacks, with similar results, confirming the reproducibility and feasibility of this approach in real-life conditions.


Discussion

The authors emphasize that this strategy is not an alternative to continuous treatment in colchicine-resistant or -intolerant patients. Rather, it should be considered a “rescue” therapy, allowing rapid interruption of occasional acute attacks, reduction of pain, avoidance of emergency department visits, decreased absenteeism, and improved quality of life.


Conclusion

This prospective study demonstrates the efficacy and safety of a single, early injection of anakinra to significantly shorten FMF attacks (both classical and heterozygous forms) in adults. A randomized controlled trial is currently underway to confirm these findings and to better define the optimal role of this strategy within the therapeutic armamentarium.

 
 
 

Anakinra-Associated Systemic Amyloidosis

Updated: Dec 10, 2024

First author: S Alehashemi

Journal : Arthritis and Rheumatology

Reference : DOI : 10.1002/art.42664



This article reports the first case of iatrogenic systemic amyloidosis due to prolonged use of anakinra, an interleukin-1 receptor antagonist (IL-1Ra), in a patient suffering from multisystem inflammatory disease of neonatal onset (NOMID).


After several years of treatment with daily injections, the patient developed nodules at the injection site, a nephrotic syndrome and amyloid deposits in various organs (skin, kidney, stomach). Mass spectrometry analysis identified these deposits as being due to recombinant anakinra protein, distinct from the endogenous version.


This case highlights a rare complication of injectable biologic treatments, exacerbated by high and prolonged doses. It highlights the importance of monitoring serum protein levels, varying injection sites, and considering a change of therapy if anakinra-related amyloidosis is diagnosed.



 
 
 
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