Dataset Information

Efficacy and safety of anakinra and canakinumab in PSTPIP1-associated inflammatory diseases: a comprehensive scoping review.

ABSTRACT:

Introduction

This scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by abnormal IL-1 pathway activation due to genetic mutations.

Methods

Our methodology adhered to a pre-published protocol and involved a thorough search of MEDLINE and EMBASE databases up to February 2022, following the Joanna Briggs Institute Reviewer's Manual and the PRISMA Extension for Scoping Reviews. The review included studies reporting on IL-1 pathway inhibitor use in PAID patients.

Results

From an initial pool of 5,225 articles, 36 studies involving 43 patients were selected. The studies predominantly used observational designs and exhibited diversity in patient demographics, treatment approaches, and outcomes. Anakinra and canakinumab demonstrated promise in treating sterile pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) and PSTPIP1-associated myeloid-related-proteinemia inflammatory (PAMI) syndromes, with scant data on other syndromes. Notably, there was a paucity of information on the adverse effects of these treatments, necessitating cautious interpretation of their safety profile.

Conclusion

Current evidence on IL-1 pathway inhibitors for PAID is primarily from observational studies and remains limited. Rigorous research with larger patient cohorts is imperative for more definitive conclusions. Collaborative efforts among specialized research centers and international health initiatives are key to advancing this field.

SUBMITTER: Sanz-Cabanillas JL

PROVIDER: S-EPMC10801072 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of anakinra and canakinumab in PSTPIP1-associated inflammatory diseases: a comprehensive scoping review.

Sanz-Cabanillas Juan Luis JL Gómez-García Francisco F Gómez-Arias Pedro Jesús PJ Montilla-López Ana A Gay-Mimbrera Jesús J Ruano Juan J Isla-Tejera Beatriz B Parra-Peralbo Esmeralda E

Frontiers in immunology 20240108

<h4>Introduction</h4>This scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by abnormal IL-1 pathway activation due to genetic mutations.<h4>Methods</h4>Our methodology adhered to a pre-published protocol and involved a thorough search of MEDLINE and EMBASE databases up to February 2022, following the Joanna Briggs Institute Reviewer's Manual and the PRISMA Extension for Scoping Reviews. The ...[more]

PMID: 38259483

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Project description:BackgroundCompassionate use is a system that provides patients with expedited access to drugs which has not yet been approved, but currently in clinical trials. The investigational drugs have been authorized for compassionate use in cases involving patients suffered from life-threatening diseases and with no alternative treatments. For instance, patients afflicted with highly heterogeneous rare diseases are eligible for treatment assistance through the compassionate use program. This study aims to investigate the characteristics of compassionate use in the context of rare diseases, evaluate the efficacy and safety of compassionate use for rare diseases, and analyze the marketing approval of investigational drugs.MethodsThe case reports/case series of compassionate use were collected by conducting searches on Embase, PubMed, Web of Science, CNKI and SinoMed, spanning from January 1991 to December 2022. Subsequently, two independent reviewers evaluated these reports. Case reports/case series that met the inclusion criteria and exclusion criteria were enrolled. Information extracted from these reports and series included patients' basic information, the investigational drug's name, its indication, adverse events, treatment outcomes, and other relevant data.ResultsA total of forty-six studies were included, encompassing 2079 patients with an average age of 38.1 years. Thirty-nine different drugs were involved in 46 studies. Furthermore, neoplasms emerged as the most common therapeutic area for compassionate use in rare disease management (23/46, 50.0%). Regarding the treatment efficacy, four studies reported successful disease resolution, while 35 studies observed symptom improvement among patients. Conversely, four studies documented no significant effects on patients' diseases. Moreover, one study reported worsened results following compassionate use, while the efficacy was not described in 2 studies. Adverse events were reported in 31 studies (67.4%) because of the compassionate use, while no adverse events occurred in 13 studies (28.3%). In other 2 studies, there was no description about whether treatment-emergent adverse events (TEAEs) were happened. 136 patients (6.5%) had Grade 5 adverse events (death), of which 19 deaths (0.9%) were considered to be related to compassionate use. Furthermore, the investigational drugs in 33 studies (33/46, 71.7%) received new drug approval at the end of January 31, 2023.The time lag from the start of the compassionate use to the formal approval of the investigational drug was 790.5 (IQR 359-2199.3) days. We found that in 11 studies, encompassing 9 different drugs, some compassionate use indications had not received regulatory authorities at the end of January 31, 2023.ConclusionThe current status of compassionate use for rare diseases was clarified systematically in this study. Compassionate use of investigational drug is a significant treatment option for rare disease. In general, compassionate use appears to demonstrate favorable efficacy in the context of rare diseases, with a significant proportion of compassionate use drugs subsequently receiving marketing approval. However, the safety of drugs for compassionate use cannot be fully evaluated due to the safety data were not covered in some enrolled studies. Therefore, the establishment of an adverse event reporting system specific to compassionate use is warranted.

Project description:IntroductionThe blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety and efficacy of canakinumab for patients with uAIDs.MethodsInformation on 32 patients with uAIDs was retrospectively collected and analyzed. Next-generation sequencing and Federici criteria were used for the exclusion of the known monogenic AID.ResultsThe median age of the first episode was 2.5 years (IQR: 1.3; 5.5), that of the disease diagnosis was 5.7 years (IQR: 2.5;12.7), and that of diagnostic delay was 1.1 years (IQR: 0.4; 6.1). Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%). Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%). Canakinumab induced complete remission in 27 patients (84%) and partial remission in one patient (3%). Two patients (6%) were primary non-responders, and two patients (6%) further developed secondary inefficacy. All patients with partial efficacy or inefficacy were switched to tocilizumab (n = 4) and sarilumab (n = 1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported Serious Adverse Events (SAEs). The patients experienced non-frequent mild respiratory infections at a rate that is similar as before canakinumab is administered. Additionally, one patient developed leucopenia, but it was not necessary to stop canakinumab for this patient.ConclusionThe treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.

Project description:PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, previously known as Hyperzincemia/Hypercalprotectinemia (Hz/Hc) syndrome, is a recently described, rare auto-inflammatory disorder caused by specific deleterious variants in the PSTPIP1 gene (p.E250K and p.E257K). The disease is characterized by chronic systemic inflammation, cutaneous and osteoarticular manifestations, hepatosplenomegaly, anemia, and neutropenia. Increased blood levels of MRP 8/14 and zinc distinguish this condition from other PSTPIP1-associated inflammatory diseases (PAID). The aim of this systematic review is to provide a comprehensive overview of the disease phenotype, course, treatment, and outcome based on reported cases. This systematic review adheres to the PRISMA guidelines (2020) for reporting. A literature search was performed in Embase, Medline, and Web of Science on 13 October 2022. The quality of the case reports and case series was assessed using the JBI checklists. Out of the 43 included patients with PAMI syndrome, there were 24 females and 19 males. The median age at onset was 3.9 years. The main clinical manifestations included anemia (100%), neutropenia (98%), cutaneous manifestations (74%), osteoarticular manifestations (72%), splenomegaly (70%), growth failure (57%), fever (51%), hepatomegaly (56%), and lymphadenopathy (39%). Systemic inflammation was described in all patients. Marked elevation of zinc and MRP 8/14 blood levels were observed in all tested patients. Response to treatment varied and no consistently effective therapy was identified. The most common therapeutic options were corticosteroids (N = 30), anakinra (N = 13), cyclosporine A (N = 11), canakinumab (N = 6), and anti-TNF (N = 14). Hematopoietic stem cell transplantation has been recently reported to be successful in five patients. Our review highlights the key characteristics of PAMI syndrome and the importance of considering this disease in the differential diagnosis of patients presenting with early-onset systemic inflammation and cytopenia.

Dataset Information

Efficacy and safety of anakinra and canakinumab in PSTPIP1-associated inflammatory diseases: a comprehensive scoping review.

Introduction

Methods

Results

Conclusion

Publications

Efficacy and safety of anakinra and canakinumab in PSTPIP1-associated inflammatory diseases: a comprehensive scoping review.

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