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Deficiencies in interleukin (IL)-1 receptor (IL-R) antagonist (DIRA) and IL-36R antagonist (DITRA) are rare genetic autoinflammatory diseases related to alterations in antagonists of the IL-1 pathway. IL-1 antagonists may represent therapeutic alternatives. Here, we aim to provide a scoping review of knowledge on use of IL-1-targeting drugs in DIRA and DITRA.
An a priori protocol was published, and the study was conducted using the methodology described in the Joanna Briggs Institute Reviewer’s Manual and the recently published PRISMA Extension for Scoping Review statement. A three-step search using MEDLINE and EMBASE databases until March 2018 with additional hand searching was performed. Data charting was performed. The search, article selection, and data extraction were carried out by two researchers independently.
Twenty-four studies on use of anti-IL-1 drugs were included [15 studies including patients with diagnosis of DIRA (n = 19) and 9 studies including patients with diagnosis of DITRA (n = 9)]. Most studies followed a multicenter observational design. Among all patients who received treatment with anti-IL-1 drugs, nine and four mutations in IL1RN and IL36RN were found, respectively. Patients with DIRA were treated with anakinra (n = 17), canakinumab (n = 2), or rinolacept (n = 6). All patients with DITRA were treated with anakinra, and only one case was also treated with canakinumab. Time-to-response frequencies were evaluated as immediate, short, and medium–long term for DIRA (17/17, 15/17, and 9/10, respectively) and DITRA (7/9, 3/9, and 2/9, respectively). Most DITRA patients in whom anti-IL-1 treatment failed experienced good response to anti-tumor necrosis factor alpha or anti-IL-12/23 drugs. The safety profiles of treatments were similar in both diseases.
Evidence on use of anti-IL-1 drugs in DIRA and DITRA is scarce and based on observational studies. Larger studies with better methodological quality are needed to increase confidence in use of these drugs in patients with DIRA and DITRA.
Supplementary material 1 (PDF 412 kb)13555_2018_269_MOESM1_ESM.pdf
Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009;360:2426–37. CrossRef
Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87:2095–147. PubMed
Palomo J, Dietrich D, Martin P, Palmer G, Gabay C. The interleukin (IL)-1 cytokine family-balance between agonists and antagonists in inflammatory diseases. Cytokine. 2015;76:25–37. CrossRef
Kumar S, McDonnell PC, Lehr R, et al. Identification and initial characterization of four novel members of the interleukin-1 family. J Biol Chem. 2000;275:10308–14. CrossRef
Reddy S, Jia S, Geoffrey R, et al. An autoinflammatory disease due to homozygous deletion of the IL1RN locus. N Engl J Med. 2009;360:2438–44. CrossRef
Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365:620–8. CrossRef
Hallegua DS, Weisman MH. Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases. Ann Rheum Dis. 2002;61:960–7. CrossRef
Economides AN, Carpenter LR, Rudge JS, et al. Cytokine traps: multi-component, high-affinity blockers of cytokine action. Nat Med. 2003;9:47–52. CrossRef
Novartis Pharmaceuticals Corporation. Prescribing information for ILARIS (canakinumab). http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125319s047lbl.pdf. Accessed on 31 Aug 2018.
Hong DS, Janku F, Naing A, et al. Xilonix, a novel true human antibody targeting the inflammatory cytokine interleukin-1 alpha, in non-small cell lung cancer. Investig New Drugs. 2015;33:621–31. CrossRef
Colquhoun HL, Levac D, O’Brien KK, et al. Scoping reviews: time for clarity in definition, methods, and reporting. J Clin Epidemiol. 2014;67:1291–4. CrossRef
Al-Almaie SM, Al-Baghli NA. Evidence based medicine: an overview. J Fam Community Med. 2003;10:17–24.
Gómez-García F, Ruano J, Gay-Mimbrera J, et al. A scoping review protocol to explore the use of interleukin-1-targeting drugs for the treatment of dermatological diseases: indications, mechanism of action, efficacy, and safety. Dermatol Ther (Heidelb). 2018;8:195–202. CrossRef
Aromataris E, Munn Z (Editors). Joanna Briggs Institute reviewer’s manual. The Joanna Briggs Institute, 2017. Available from https://reviewersmanual.joannabriggs.org/. Accessed 18 Aug 2018.
Carapito R, Isidor B, Guerouaz N, et al. Homozygous IL36RN mutation and NSD1 duplication in a patient with severe pustular psoriasis and DITRA-unrelated symptoms. Br J Dermatol. 2015;172:302–5. CrossRef
Zimmer C, Moll M, Rieber N, Goldbach-Mansky R, Aksentijevich I, Kuemmerle-Deschner J. IL-1 inhibition in a patient with polymorphism in the interleukin 1-receptor type 1 gene and clinical phenotype of CRMO/DIRA. Ann Rheum Dis. 2013;71(SUPPL. 3):257.
Cuperus W, Koevoets R, van der Smagt JJ, et al. Juvenile interleukin-36 receptor antagonist deficiency (DITRA) with c.80T > C (p.Leu27Pro) mutation successfully treated with etanercept and acitretin. JAAD Case Rep. 2018;4(2):192–5. CrossRef
Capusan TM, et al. Combined therapy in 2 cases of pustular generalized psoriasis with IL36RN gene mutations. Pediatric Dermatol. 2017;34(Supplement 2):S46.
Cordoro KM, Ucmak D, Hitraya-Low M, Rosenblum MD, Liao W. Response to interleukin (IL)-17 inhibition in an adolescent with severe manifestations of IL-36 receptor antagonist deficiency (DITRA). JAMA Dermatol. 2017;153:106–8. CrossRef
Caorsi R, Minoia F, Viglizzo G, et al. The therapeutic challenge of DITRA syndrome. Pediatr Rheumatol. 2017;15(Supplement):1.
Glerup M, Veirum J, Iversen L, Christiansen M, Herlin T. Generalized pustular psoriasis in infant with heterozygous mutation in the IL36RN gene successfully treated with infliximab. Pediatr Rheumatol Online J. 2014;12(Suppl 1):P79. CrossRef
Mendonca LO, Malle L, Donovan FX, et al. Deficiency of interleukin-1 receptor antagonist (DIRA): report of the first Indian patient and a novel deletion affecting IL1RN. J Clin Immunol. 2017;37:445–51. CrossRef
Panju AH, Bell CM. Policy alternatives for treatments for rare diseases. CMAJ. 2010;182(17):E787–92. CrossRef
Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D, CARE Group. The CARE guidelines: consensus-based clinical case reporting guideline development. Glob Adv Health Med. 2013;2:38–43. CrossRef
https://www.ncbi.nlm.nih.gov/clinvar?term=147679[MIM]. Accessed 12 Sep 2018.
https://www.ncbi.nlm.nih.gov/clinvar?term=605507[MIM]. Accessed 12 Sep 2018.
Minkis K, Aksentijevich I, Goldbach-Mansky R, et al. Interleukin 1 receptor antagonist deficiency presenting as infantile pustulosis mimicking infantile pustular psoriasis. Arch Dermatol. 2012;148:747–52. CrossRef
Schnellbacher C, Ciocca G, Menendez R, et al. Deficiency of interleukin-1 receptor antagonist responsive to anakinra. Pediatr Dermatol. 2013;30:758–60. CrossRef
Mendoní ALO, et al. A case report of a novel compound heterozygous mutation in a Brazilian patient with deficiency of IL1RA (DIRA). J Clin Immunol. 2017;37(Supplement 1):S19.
Berdeli A, Sözeri B, Gerceker Türk B, Oz A, Mir S. Turkish DIRA patient with novel IL1RN gene mutation. Pediatr Rheumatol. 2015;13(Suppl 1):P181. CrossRef
Ulusoy E, Karaca NE, El-Shanti H, Kilicoglu E, Aksu G, Kutukculer N. Interleukin-1 receptor antagonist deficiency with a novel mutation; late onset and successful treatment with canakinumab: a case report. J Med Case Rep. 2015;9:145. CrossRef
Thacker PG, Binkovitz LA, Thomas KB. Deficiency of interleukin-1-receptor antagonist syndrome: a rare auto-inflammatory condition that mimics multiple classic radiographic findings. Pediatr Radiol. 2012;42:495–8. CrossRef
Jesus AA, Osman M, Silva CA, et al. A novel mutation of IL1RN in the deficiency of interleukin-1 receptor antagonist syndrome: description of two unrelated cases from Brazil. Arthritis Rheum. 2011;63:4007–17. CrossRef
Stenerson M, Dufendach K, Aksentijevich I, Brady J, Austin J, Reed AM. The first reported case of compound heterozygous IL1RN mutations causing deficiency of the interleukin-1 receptor antagonist. Arthritis Rheum. 2011;63:4018–22. CrossRef
Hüffmeier U, Wätzold M, Mohr J, Schön MP, Mössner R. Successful therapy with anakinra in a patient with generalized pustular psoriasis carrying IL36RN mutations. Br J Dermatol. 2014;170:202–4. CrossRef
Boehner A, Navarini AA, Eyerich K. Generalized pustular psoriasis—a model disease for specific targeted immunotherapy, systematic review. Exp Dermatol. 2018;27:1067–77. CrossRef
Akiyama M, Takeichi T, McGrath JA, Sugiura K. Autoinflammatory keratinization diseases. J Allergy Clin Immunol. 2017;140:1545–7. CrossRef
Akiyama M, Takeichi T, McGrath JA, Sugiura K. Autoinflammatory keratinization diseases: an emerging concept encompassing various inflammatory keratinization disorders of the skin. J Dermatol Sci. 2018;90:105–11. CrossRef
- Scoping Review on Use of Drugs Targeting Interleukin 1 Pathway in DIRA and DITRA
Juan L. Sanz-Cabanillas
Antonio Vélez-García Nieto
- Springer Healthcare
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