Scoping Review on Use of Drugs Targeting Interleukin 1 Pathway in DIRA and DITRA

Abstract

IntroductionDeficiencies 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.MethodsAn 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.ResultsTwenty-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.ConclusionsEvidence 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.Electronic supplementary materialThe online version of this article (10.1007/s13555-018-0269-7) contains supplementary material, which is available to authorized users.

IL-1 Family Antagonists in Mouse and Human Skin Inflammation

“…However, targeting other cytokines than those specifically associated with a given genetic mutation has also proven to be effective. For example, patients with DITRA responded favorably to IL-1 inhibition, most likely due to the production of IL-1 downstream of excessive IL-36 signaling ( 146 , 269 ). In contrast, the effect of IL-36 blockade in patients with excessive IL-1 signaling, such as in DIRA, has not been tested.…”

Deficiency of Interleukin-1 Receptor Antagonist: A Case with Late Onset Severe Inflammatory Arthritis, Nail Psoriasis with Onychomycosis and Well Responsive to Adalimumab Therapy

“…A soluble decoy receptor, rilonacept, and another neutralizing human monoclonal anti-IL-1 β antibody, canakinumab, were also approved. Canakinumab that can be administered every 4-6 weeks began to be a better treatment choice [13]. Our previous patient had responded excellently to canakinumab treatment [7].…”

Chronic Nonbacterial Osteomyelitis in Children

“…The use of other IL-1 blockers such as canakinumab and rilonacept has showed similar results. To date, there is no available study that compares the long-term efficacy among the different IL-1 blockers [ 53 , 54 , 55 , 56 , 57 , 58 ].…”