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Review
. 2024 Feb 10;13(4):1026.
doi: 10.3390/jcm13041026.

Analysis of Anakinra Therapy for the Deficiency of Interleukin-1 Receptor Antagonist through Clinical Evidence

Kathryn Pillai  1 , Joshua Pillai  2 , Jun Ling  1
Affiliations
Review

Analysis of Anakinra Therapy for the Deficiency of Interleukin-1 Receptor Antagonist through Clinical Evidence

Kathryn Pillai et al. J Clin Med. .

Abstract

Background: Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare life-threatening autosomal recessive autoinflammatory disease with symptoms including but not limited to osteomyelitis, periostitis, and systemic inflammation. DIRA is developed from the loss-of-function biallelic mutations of the IL1RN gene that encodes IL-1 receptor antagonist (IL-1RA), leading to the unchecked pro-inflammatory signaling and subsequent systemic inflammation. Thus, anakinra as the recombinant IL-1RA has become the primary drug to treat DIRA. Although anakinra has been effective for the complete remission of DIRA, it has also shown various side effects. To confirm the efficacy and safety issues associated with DIRA treatment, we conducted a literature review and secondary data analysis to enhance our understanding on this important topic.

Methods: Through comprehensive literature search, we have identified 15 papers with 25 patients studied. The demographic, clinical, and genetic data were extracted, followed by statistical analysis to support the physiological mechanisms of anakinra treatment.

Results: Through the literature review and data analysis, it was found that 88% of patients had complete clinical remission of DIRA upon continual treatment with anakinra; patients had a mean improvement of Hemoglobin (+3.18 g/dL), Erythrocyte Sedimentation Rate (-53.4 mm/h), and C-reactive Protein (-135.45 mg/L) levels, suggesting that the improvement of hematopoietic function and inflammation is a mechanism for anakinra treatment. Various genetic variants were also identified from the patient data that cause the loss of function of IL-1RA, providing real patient genomic data to support the anakinra treatment.

Conclusions: Considering the inconsistency and certain variations from clinical research influenced by specific conditions, this review along with the data analysis confirms the efficacy and safety of anakinra treatment for DIRA.

Keywords: IL-1RA; IL-1RN; anakinra; autoinflammatory diseases; deficiency of interluekin-1 receptor antagonist (DIRA).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Literature search and screening process for this review. A total of 544 studies were retrieved from all databases. All studies were screened. Seven duplicate articles were identified and removed. Full-text articles were assessed for eligibility and 214 studies were removed due to ineligible language, design, or criteria. In total, 15 studies were finally selected for this review.
Figure 2
Figure 2
Statistical analyses of laboratory results of anakinra therapy. (A) Comparison of HB levels pre- and post-treatment. (B) Comparison of CRP levels pre- and post-treatment. (C) Comparison of ESR pre- and post-treatment. p values were determined from the Wilcoxon rank-sum test. The dataset for all laboratory data is reported in Supplemental Materials.
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Grants and funding

This research was partially supported by internal funds.
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