OBJECTIVE: Idiopathic recurrent pericarditis (IRP) is defined by recurring episodes of pericardial inflammation without a known cause. This study investigates the safety and efficacy of anakinra, an interleukin‑1 inhibitor, as a successful therapy for IRP in cases resistant to conventional treatment.
METHODS: A retrospective evaluation of patients treated at our autoinflammatory center between 2011 and 2023 was conducted. Patient files were examined for demographic, clinical, and treatment response data, including nonsteroid anti-inflammatory drugs (NSAIDs), corticosteroids, and colchicine. Monogenic autoinflammatory disease screening was performed for Mediterranean Fever (MEFV), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase (MVK), nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), and nucleotide-binding oligomerization domain-containing protein 2 (NOD2). Patients who experienced multiple episodes of pericarditis were diagnosed with recurrent pericarditis. The study evaluated anakinra treatment in IRP patients unresponsive to conventional therapy.
RESULTS: The study included 21 participants, 9 (42.9%) female and 12 (57.1%) male. The average age of the participants was 43.1 ± 16.5 years. The MEFV mutation analysis revealed that 2 (9.5%) had a mutation in exon 10 and 4 (19.0%) had one in exon 2. Out of the 16 cases, 15 successfully discontinued steroid treatment. Four patients (19.0%) experienced injection site reactions. C‑reactive protein (CRP) levels were measured at an average of 196 ± 67.8 mg/l before and 2.6 ± 3.15 mg/l after anakinra treatment.
CONCLUSIONS: In conclusion, the study adds to the growing evidence for the efficacy of interleukin-1 inhibitors, such as anakinra, as a promising treatment modality for IRP in cases resistant to conventional treatment.
UNASSIGNED: ZIEL: Die idiopathische rezidivierende Perikarditis (IRP) ist charakterisiert durch rezidivierende Episoden perikardialer Entzündung ohne bekannte Ursache. In der vorliegenden Studie wurde die Sicherheit und Wirksamkeit von Anakinra, einem Interleukin-1-Inhibitor, als einer erfolgreichen Therapie der IRP in Fällen untersucht, die sich als refraktär auf die herkömmliche Behandlung erwiesen haben.
METHODS: Dazu wurde eine retrospektive Untersuchung von Patienten durchgeführt, die im Zentrum für Autoinflammation der Autoren zwischen 2011 und 2023 behandelt worden waren. Die Patientenakten wurden in Bezug auf demografische und klinische Daten sowie auf Daten zum Therapieansprechen hin untersucht, einschließlich nichtsteroidaler antientzündlicher Medikamente (NSAID), Kortikosteroide und Colchicin. Ein Screening auf monogene autoinflammatorische Erkrankungen wurde hinsichtlich MEFV, TRAPS, MVK, NLRP3 und NOD2 durchgeführt. Bei Patienten mit mehreren Perikarditisepisoden wurde die Diagnose einer rezidivierenden Perikarditis gestellt. In der Studie wurde die Behandlung mit Anakinra bei IRP-Patienten, die nicht auf die herkömmliche Therapie ansprachen, untersucht.
UNASSIGNED: In die Studie wurden 21 Teilnehmer einbezogen, 9 (42,9 %) weiblich und 12 (57,1 %) männlich. Das Durchschnittsalter der Teilnehmer betrug 43,1 ± 16,5 Jahre. Die MEFV-Mutationsanalyse ergab, dass 2 (9,5 %) Personen eine Mutation in Exon 10 und 4 (19,0 %) eine in Exon 2 aufwiesen. Von den 16 Fällen setzten 15 die Steroidtherapie erfolgreich ab. Bei 4 Patienten (19,0 %) kam es zu Reaktionen an der Injektionsstelle. Die Werte für C‑reaktives Protein (CRP) betrugen im Durchschnitt 196 ± 67,8 mg/l vor und 2,6 ± 3,15 mg/l nach Anakinratherapie.
UNASSIGNED: Diese Studie leistet also einen Beitrag zu der wachsenden Evidenz für die Wirksamkeit von Interleukin-1-Inhibitoren wie Anakinra als vielversprechender Behandlungsmodalität für IRP in Fällen, die refraktär auf die herkömmliche Therapie sind.

OBJECTIVE: Whipple\'s disease (WD) results from infection of the bacteria Tropheryma whipplei (TW). This disease is characterized by macrophage infiltration of intestinal mucosa and primarily affects Caucasian males. Genetic studies of host susceptibility are scarce. Nucleotide-binding oligomerization domain containing protein 2 (NOD2) is an innate immune sensor, resides mainly in monocytes/macrophages and contributes to defence against infection and inflammatory regulation. NOD2 mutations are associated with autoinflammatory diseases. We report the association of NOD2 mutations with TW and WD for the first time.
METHODS: A multicentre, retrospective study of three patients with WD was conducted. Patients received extensive multidisciplinary evaluations and were cared for by the authors. NOD2 and its association with infection and inflammation were schematically represented.
RESULTS: All patients were Caucasian men and presented with years of autoinflammatory phenotypes, including recurrent fever, rash, inflammatory arthritis, gastrointestinal symptoms and elevated inflammatory markers. All patients underwent molecular testing using a gene panel for periodic fever syndromes and were identified to carry NOD2 mutations associated with NOD2-associated autoinflammatory disease. Despite initially negative gastrointestinal evaluations, repeat endoscopy with duodenal tissue biopsy ultimately confirmed WD. After initial ceftriaxone and maintenance with doxycycline and/or HCQ, symptoms were largely controlled, though mild relapses occurred in follow-up.
CONCLUSIONS: Both NOD2 and TW/WD are intensively involved in monocytes/macrophages. WD is regarded as a macrophage disease. NOD2 leucin-rich repeat-associated mutations in monocytes/macrophages cause functional impairment of these cells and consequently may make the host susceptible for TW infection and WD, especially in the setting of immunosuppression.

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease deriving from the hair follicles. The formation of inflammatory nodules, abscesses, fistulas, and sinus tracts is characterized by a large inflow of key pro-inflammatory mediators, such as IFN-γ, TNF-α, IL-1, IL-17, and IL-12/23. Adalimumab is currently the only Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved biologic therapy for moderate to severe HS in adults and adolescents. However, the long-term effectiveness of this TNF-α inhibitor in HS patients has shown to be highly variable. This review aims to review the evidence for emerging therapies that target the main pro-inflammatory cytokines in HS pathogenesis. A review of the literature was conducted, using the PubMed and Google Scholar repositories, as well as Clinicaltrials.gov. Presently, the most promising biologics in phase III trials are anti-IL-17 antibodies, secukinumab, and bimekizumab. Furthermore, an anti-IL-1 biologic, bermekimab, is currently in phase II trials, and shows encouraging results. Overall, the clinical efficacies of all new targeted therapies published up to this point are limited. More studies need to be performed to clarify the precise molecular pathology, and assess the efficacy of biological therapies for HS.

Objectives: The major role of interleukin (IL)-1 in the pathogenesis of hereditary recurrent fever syndromes favored the employment of targeted therapies modulating IL-1 signaling. However the best use of IL1 inhibitors in terms of dosage is difficult to define at present. Methods: In order to better understand the use of IL1 inhibitors in a real-life setting, our study assessed the dosage regimens of French patients with one of the four main hereditary recurrent fever syndromes (Familial Mediterranean Fever (FMF), TNF receptor associated periodic syndrome (TRAPS), cryopyrin associated periodic fever (CAPS) and mevalonate kinase deficiency). The patients were retrieved retrospectively from the JIR cohort, an international platform gathering data of patients with pediatric inflammatory diseases. Results: Forty five patients of the JIR cohort with a hereditary recurrent fever syndrome had received at least once an IL1 inhibitor (anakinra or canakinumab). Of these, 43% received a lower dosage than the one suggested in the product recommendations, regardless of the type of the IL1 inhibitor. Especially patients with FMF and TRAPS seemed to need lower treatment regimens; in our cohort none of the FMF or TRAPS patients received an intensified dose of IL-inhibitor. On-demand treatment with a short half-life IL-1 inhibitor has also been used successfully for some patients with one of these two conditions The standard dose was given to 42% of the patients; whereas an intensified dose of IL-1 inhibitors was given to 15% of the patients (44% of CAPS patients and 17% of mevalonate kinase deficiency patients). In our cohort each individual patient\'s need for treatment seemed highly variable, ranging from on demand treatment regimens to intensified dosage maintenance therapies depending on the activity and the severity of the underlying disease. Conclusion: IL-1 inhibitors are a good treatment option for patients with a hereditary recurrent fever syndrome, but the individual need of the dosage of IL-1 inhibitors to control the disease effectively seems highly variable. Severity, activity but also the type of the underlying disease, belong to the parameters underpinning the treat-to-target strategy implemented in an everyday life practice.

BACKGROUND: Tumour necrosis factor-alpha inhibitors (anti-TNFα) and anakinra are monoclonal antibodies against pro-inflammatory cytokines overexpressed in many systemic inflammatory diseases. In Australia, they are registered for the treatment of several rheumatological, gastroenterological and dermatological indications. Despite increasing observational evidence for their use in off-label indications, there is a paucity of outcome research from the Australian hospital sector.
OBJECTIVE: To describe the off-label use of anti-TNFα and anakinra at a tertiary referral hospital in Queensland, Australia and consideration of a drug register to inform future clinical decision-making.
METHODS: We performed an in-depth retrospective chart audit of off-label treatment with anti-TNFα or anakinra at the Royal Brisbane and Women\'s Hospital from mid-2010 to mid-2014, linking demographic, phenotypic, pathology and outcome data with these drugs.
RESULTS: Off-label use was identified in 10 patients. The most frequent indications were sarcoidosis and dermatological conditions. Three patients required sequential therapy with a second anti-TNFα (total responses = 13). Complete response occurred in 46%, partial response in 38% and primary non-response in 8%. Response was unable to be determined in 8%. We recorded 14 adverse events (infections most common).
CONCLUSIONS: This study suggests that anti-TNFα may be beneficial for some off-label indications (e.g. sarcoidosis). However, the observational design of this study (and pre-existing research) limits the ability to infer causality and generalise results. We propose the creation of a mandatory drug register to monitor off-label use. Whilst comparative efficacy cannot be established without a matched placebo arm, a register would enable some reporting on effectiveness in rare diseases and identify infrequent but serious adverse events.