- Biologics in SAPHO syndrome: A systematic review. [Review]
- SASemin Arthritis Rheum 2018 Apr 17
- CONCLUSIONS: In SAPHO patients not responding to conventional treatment, TNF blockers appear to be the first choice. In patients failing TNF blockers, IL-1 inhibitors and biologics targeting the IL-17/IL-23 axis could be used.
- Safety profile of the interleukin-1 inhibitors anakinra and canakinumab in real-life clinical practice: a nationwide multicenter retrospective observational study. [Journal Article]
- CRClin Rheumatol 2018 May 17
- A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and ...
A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and adults, based on data from a real-life setting. Demographic, clinical, and therapeutic data from patients treated with ANA and CAN were retrospectively collected and analyzed. Four hundred and seventy five patients were enrolled; ANA and CAN were prescribed in 421 and 105 treatment courses, respectively. During a mean follow-up of 24.39 ± 27.04 months, 89 adverse events (AE) were recorded; 13 (14.61%) were classified as serious AE (sAE). The overall estimated rate of AE and sAE was 8.4 per 100 patients/year. Safety concerns were more frequent among patients aged ≥ 65 years compared with patients < 16 years (p = 0.002). No differences were detected in the frequency of safety concerns between monotherapy and combination therapy with immunosuppressants (p = 0.055), but a significant difference was observed when injection site reactions were excluded from AE (p = 0.01). No differences were identified in relation to gender (p = 0.462), different lines of biologic therapy (p = 0.775), and different dosages (p = 0.70 ANA; p = 0.39 CAN). The overall drug retention rate was significantly different according to the occurrence of safety concerns (p value < 0.0001); distinguishing between ANA and CAN, significance was maintained only for ANA (p < 0.0001 ANA; p > 0.05 CAN). Treatment duration was the only variable associated with onset of AE (OR = 0.399 [C.I. 0.250-0.638], p = 0.0001). ANA and CAN have shown an excellent safety profile; the risk for AE and sAE tends to decrease over time from the start of IL-1 inhibition.
- Resolution of femoral metaphyseal dysplasia in CINCA syndrome after long-term treatment with interleukin-1 blockade. [Review]
- CRClin Rheumatol 2018 May 16
- Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare autoinflammatory disorder driven by uncontrolled hypersecretion of interleukin (IL)-1, which can be clinically depicted b...
Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare autoinflammatory disorder driven by uncontrolled hypersecretion of interleukin (IL)-1, which can be clinically depicted by striking cutaneous, neurologic, and skeletal features. Little is known about the exact pathogenesis of CINCA bone disease, which mainly involves the knees. We report a 20-year-old CINCA patient, who was consecutively treated firstly with anakinra, started at 7 years, then with full dose canakinumab, started at 17 years, focusing on the typical bone abnormalities of the syndrome: the comparison of radiographs of knees performed at 7 and 20 years has shown the disappearance of a typical metaphyseal dysplasia occurring in the femurs of this CINCA patient, regularly treated with IL-1 blockade for a period of 13 years. A review of the medical literature reveals poor information on the skeletal response of CINCA syndrome to IL-1-inhibiting therapies. This contribution confirms the protean striking effects of IL-1 blockade in this peculiar autoinflammatory disorder, showing for the first time the reversal of the characteristic CINCA metaphyseal dysplasia over long-term treatment.
- Effect of Interleukin-1 Blockade on Left Ventricular Systolic Performance and Work: A Post-Hoc Pooled Analysis of Two Clinical Trials. [Journal Article]
- JCJ Cardiovasc Pharmacol 2018 Apr 30
- CONCLUSIONS: In this post-hoc analysis, LVEes and LVEF increased significantly in patients treated with an IL-1 blocker but not in placebo-treated patients. An effect of IL-1 blockade on calculated pressure-volume area was not detected.
- Efficacy and safety of interleukin-1 antagonists in rheumatoid arthritis: a systematic review and meta-analysis. [Review]
- RIRheumatol Int 2018 May 08
- Rheumatoid arthritis patients have a high level of pro-inflammatory interleukin-1. Augmenting the blockade of interleukin-1 receptors by external interleukin-1 receptor antagonist modifies the progre...
Rheumatoid arthritis patients have a high level of pro-inflammatory interleukin-1. Augmenting the blockade of interleukin-1 receptors by external interleukin-1 receptor antagonist modifies the progression of the disease. Therefore, the aim of this study was to evaluate the clinical efficacy and safety of interleukin-1 receptor antagonist (anakinra) in the treatment of rheumatoid arthritis. Clinical trials and extension studies that compared anakinra with placebo or other medications were included. Electronic bibliographic databases: PubMed, Scopus, and Web of Sciences were searched from inception to November 2017. The American College of Rheumatology 20% (ACR20) improvement was the primary efficacy outcome measure. Total number of adverse drug events, serious adverse drug events, total treatment withdrawals, and treatment-related withdrawals were safety outcome measures. Ten studies were included in this review. One study did not fulfil quantitative criteria and was assessed qualitatively. Six clinical trials and three extension studies were included in meta-analysis. Patients treated with anakinra are 42% more likely to have ACR20 response than patients without IL-1Ra (pooled RR 1.42; 95% CI 1.01, 2.00). Patients on 30-150 mg anakinra have lower Health Assessment Questionnaire (HAQ) score than patients without IL-1Ra (SMD - 0.28; 95% CI - 0.53, - 0.03). The inflammatory marker erythrocyte sedimentation rate (ESR) was significantly lower among patients treated with 30-150 mg anakinra (SMD - 0.44; 95% CI - 0.65, - 0.23). Patients on anakinra have a 34% more risk of treatment-related withdrawal than placebo. The other parameters were not found to be statistically significant. Anakinra has a significant improvement in ACR20, HAQ, and ESR. The ACR20 response is maintained after 48 weeks of treatment. Anakinra shows higher episodes of treatment-related withdrawals than placebo.
- A Rare but Fascinating Disorder: Case Collection of Patients with Schnitzler Syndrome. [Journal Article]
- CRCase Rep Rheumatol 2018; 2018:7041576
- CONCLUSIONS: Schnitzler syndrome is a rare and underdiagnosed disorder. High suspicion should be maintained in patients with chronic urticaria-like dermatoses, intermittent fevers, and arthralgias. A serum protein electrophoresis and immunofixation should be performed in these patients. The diagnosis is important to recognize as Schnitzler syndrome is associated with malignancy. A lymphoproliferative disorder develops in about 20% of patients at an average of 7.6 years after onset of symptoms. Thus, patients warrant long-term follow-up. IL-1 inhibitors are extremely effective in relieving symptoms and are considered first line therapy.
- The role of IL-1 in postprandial fatigue. [Journal Article]
- MMMol Metab 2018 Apr 12
- CONCLUSIONS: We conclude that IL-1 is involved in the regulation of postprandial fatigue under physiologic conditions in lean and obese individuals. It remains to be shown whether this effect translates into clinical relevant effects.
- Schnitzler syndrome associated with hairy cell leukemia presenting with chronic urticaria and arthralgias. [Journal Article]
- JCJAAD Case Rep 2018; 4(4):386-389
- Autophagy and LAP in the Fight against Fungal Infections: Regulation and Therapeutics. [Review]
- MIMediators Inflamm 2018; 2018:6195958
- Phagocytes fight fungi using canonical and noncanonical, also called LC3-associated phagocytosis (LAP), autophagy pathways. However, the outcomes of autophagy/LAP in shaping host immune responses app...
Phagocytes fight fungi using canonical and noncanonical, also called LC3-associated phagocytosis (LAP), autophagy pathways. However, the outcomes of autophagy/LAP in shaping host immune responses appear to greatly vary depending on fungal species and cell types. By allowing efficient pathogen clearance and/or degradation of inflammatory mediators, autophagy proteins play a broad role in cellular and immune homeostasis during fungal infections. Indeed, defects in autophagic machinery have been linked with aberrant host defense and inflammatory states. Thus, understanding the molecular mechanisms underlying the relationship between the different forms of autophagy may offer a way to identify drugable molecular signatures discriminating between selective recognition of cargo and host protection. In this regard, IFN-γ and anakinra are teaching examples of successful antifungal agents that target the autophagy machinery. This article provides an overview of the role of autophagy/LAP in response to fungi and in their infections, regulation, and therapeutic exploitation.
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- Decreased quality of life and societal impact of cryopyrin-associated periodic syndrome treated with canakinumab: a questionnaire based cohort study. [Journal Article]
- OJOrphanet J Rare Dis 2018 Apr 20; 13(1):59
- CONCLUSIONS: QoL during treatment is lower than in the general Dutch population. CAPS leads to productivity loss and absenteeism from school, and impacts the quality of life in informal caregivers.