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Introduction: Gout is a common form of acute inflammatory arthritis caused by the deposition of monosodium urate crystals within synovium of joints. This leads to severe pain, reducing quality of life for patients with this condition. Areas covered: This review summarizes the treatment of both acute flares of gout and urate-lowering therapy based on guidance from various major international societies. We have also covered new emerging therapies that have not yet reached clinical practice. Expert opinion: Standard pharmacotherapies for gout flares include the options of colchicine, NSAIDs and oral or intramuscular corticosteroids, with IL-1 inhibitors newly established as an option for flare refractory to standard therapies. Urate-lowering therapies aim to prevent gout flares, with an emphasis on treat-to-target strategy; the escalation of therapies until the target serum uric acid is reached. Initial treatments include allopurinol and febuxostat, with uricosuric agents, probenecid, sulfinpyrazone and benzbromarone, as adjuncts. There are also emerging therapies in development. However, there is increasing personalization of treatment, adjusting pharmacotherapy depending on comorbidities, such as chronic kidney disease and ischemic heart disease, as well as patient preference. [ABSTRACT FROM AUTHOR]

The objectives of the study were to present the experience of diagnosis, management, and therapy with IL-1 inhibitors in patients with Schnitzler's syndrome (SchS) according to a multicenter Russian cohort. An observational retrospective study for a 10-year period (2012–2022) involved 17 patients with SchS who were admitted to the hospital or were observed on an outpatient basis (eight women and nine men). The diagnosis of all of them corresponded to the Strasbourg diagnostic criteria. The age of patients ranged from 25 to 81 years (Me 53[46; 56]). The age at the time of the onset of the disease ranged from 20 to 72 years (Me 46[39; 54]), the duration of the disease before diagnosis ranged from 1 to 35 years (Me 6.5[3; 6]), in three patients it exceeded 10 years, in the rest it ranged from 1 to 8 years. Infectious and lymphoproliferative diseases, monogenic AIDs (CAPS, TRAPS, and HIDS) were excluded from all patients at the prehospital stage. The referral diagnosis for all of them was Still 's disease in adults. Clinical manifestations of the disease in all patients included fatigue, lethargy, fatigue, rash, and fever. In all patients, skin elements were urticular and were accompanied by itching in 6 (37.5%) patients. Bone pain was observed in 12 (70.6%) patients; arthralgias, in 16 (94.1%); arthritis, in 9 (52.9%); myalgia, in 7 (41.2%); and weight loss, in 4 (23.5%). Lymphadenopathy was detected in 6 (35.3%) patients; enlarged liver, in 6 (35.3%); pericarditis, in 4 (23.5%); angioedema, in 6 (35.3); redness and dryness in the eyes, in 3 (17.6%); sore throat, in 2 (11.8%); abdominal pain, in 1 (5.9%), distal polyneuropathy, in 2 (11.8%); paraesthesia, in 1 (5.9%); and chondritis of the auricles, in 1 (5.9%). Monoclonal gammopathy was detected in all patients with a secretion level of 2.9–15.1 g/L: IgMk (n = 10, 64.7%), less often IgMλ (n = 2), IgGk (n = 2), IgGλ (n = 1), and IgAλ (n = 1). Ben-Jones protein was not detected in any of them. All patients had an increased level of ESR and CRP. Before inclusion in the study, 16 patients received GCs (94.1%) with a temporary effect that disappeared with dose reduction or cancellation. Seven patients received cDMARDs, including methotrexate (5), hydroxychloroquine (2), and cyclophosphamide (1). All patients received NSAIDs and antihistamines, as well as biologics, including the anti-B-cell drug rituximab (1), monoclonal ABs to IgE omalizumab (2, 1 without effect and 1 with partial effect), IL-1i canakinumab (n = 10, 58.8%) subcutaneously once every 8 weeks, and anakinra (n = 4, 23.5%) subcutaneously daily. The duration of taking anakinra, which was prescribed in the test mode, ranged from 1 week to 2.5 months with a further switch to canakinumab in 3 patients. The duration of taking canakinumab at the time of analysis ranged from 7 months to 8 years. Against the background of treatment with IL-1i, 10 out of 11 (90.9%) patients received a complete response in terms of the clinical manifestations of the disease and a decrease in the level of ESR and CRP within a few days. In one patient, a partial response to the administration of anakinra was detected; however, after switching to canakinumab, the effect of treatment was finally lost. One patient received IL-6i for 8 months with an incomplete effect and a positive dynamics after switching to anakinra. Thus, anakinra was initially prescribed to four patients and changed to canakinumab in two of them; canakinumab was started as the first drug in seven patients. Treatment with anakinra was continued in two patients; with canakinumab, in nine patients. In one patient, due to the persistent absence of relapses, the interval between canakinumab injections was increased to 5 months without signs of reactivation; however, subsequently, against the background of stress and relapses of the disease, the intervals were reduced to 4 months. A healthy child was born by the same patient on the background of treatment. The tolerability of therapy was satisfactory in all patients, no SAEs were noted. SchS is a rare multifactorial/non-monogenic AID that should be differentiated from a number of rheumatic diseases and other AIDs. The onset in adulthood, the presence of recurrent urticarial rashes in combination with fever and other manifestations of a systemic inflammatory response are indications for examination for monoclonal secretion. The use of short- or long-acting IL-1i is a highly effective and safe option in the treatment of such patients. [ABSTRACT FROM AUTHOR]

Abstract Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, is closely linked to persistent low-grade inflammation, significantly contributing to its development and progression. This review provides a comprehensive examination of the inflammatory mechanisms underlying T2DM, focusing on the role of the NLRP3 inflammasome and interleukin-1β (IL-1β) in mediating inflammatory responses. We discuss the therapeutic potential of IL-1 inhibitors and colchicine, highlighting their mechanisms in inhibiting the NLRP3 inflammasome and reducing IL-1β production. Recent studies indicate that these agents could effectively mitigate inflammation, offering promising avenues for the prevention and management of T2DM. By exploring the intricate connections between metabolic disturbances and chronic inflammation, this review underscores the need for novel anti-inflammatory strategies to address T2DM and its complications.

Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, is closely linked to persistent low-grade inflammation, significantly contributing to its development and progression. This review provides a comprehensive examination of the inflammatory mechanisms underlying T2DM, focusing on the role of the NLRP3 inflammasome and interleukin-1β (IL-1β) in mediating inflammatory responses. We discuss the therapeutic potential of IL-1 inhibitors and colchicine, highlighting their mechanisms in inhibiting the NLRP3 inflammasome and reducing IL-1β production. Recent studies indicate that these agents could effectively mitigate inflammation, offering promising avenues for the prevention and management of T2DM. By exploring the intricate connections between metabolic disturbances and chronic inflammation, this review underscores the need for novel anti-inflammatory strategies to address T2DM and its complications. [ABSTRACT FROM AUTHOR]

Acne inversa is a chronic, progressive inflammatory skin disease. It is characterized by the occurrence of relapsing, painful, deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. The disease significantly affects patients’ quality of life and is often associated with severe, debilitating pain and depression. Pro-inflammatory cytokines such as TNF-α, interleukin 17 (IL-17), IL-23, IL-12, IL-1α, and IL-1β play a significant role in the pathogenesis of hidradenitis suppurativa. Treatment is difficult and often ineffective, based on both surgical and pharmacological methods. Biologic drugs in hidradenitis suppurativa are the subject of many clinical trials and may be effective in patients for whom other therapies have failed. The first biological drug approved by the Food and Drug Administration for the treatment of hidradenitis suppurativa was the TNF-α inhibitor — adalimumab. The advancement of knowledge of immune mechanisms in the pathogenesis of hidradenitis suppurativa has allowed the development of clinical trials of new therapeutic targets. In 2023, the Food and Drug Administration (FDA) approved the IL-17 inhibitor — secukinumab as the second biological drug in hidradenitis suppurativa. The aim of this review is an update of the biological treatment and its effectiveness in hidradenitis suppurativa. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to evaluate the clinical, laboratory and genetic characteristics and outcomes of patients with AA amyloidosis. Methods Patients followed up in a tertiary referral centre in Turkey with the diagnosis of inflammatory rheumatic diseases and immunohistologically proven AA amyloidosis were included in the study and retrospectively analysed. Results Among 184 patients with the diagnosis of AA amyloidosis, 174 (83 female, 91 male) were included in the analysis. The most common cause of AA amyloidosis was FMF (78.7%), and 91% of FMF-AA amyloidosis patients were carrying the p.M694V variant (74.1% homozygous). AA amyloidosis was identified earlier in patients with homozygous or compound heterozygous MEFV exon 10 variants compared with the heterozygous patients (27, 30 and 41 years, respectively). Patients with an estimated glomerular filtration rate <60 ml/min at admission had a higher frequency of progression to end-stage renal disease (P  < 0.001). The overall mortality rate was 15.3% and it increased gradually in association with the amyloid burden (10% in patients with renal, 15% in renal + gastrointestinal and 43% in those with additional cardiac involvement). Renal findings responded completely to treatment in 31% of the patients, a partial response was observed in 4%, a stable course in 23.6% and progression in 38.5%. Amyloid storm was identified in nine patients and was found to be associated with increased mortality within 1 year. Conclusion FMF patients still constitute the majority of AA amyloidosis patients in Turkey. The MEFV genotype and associated inflammatory load may affect the age of onset of AA amyloidosis, and earlier diagnosis and stricter follow-up and treatment may delay progression of the disease. [ABSTRACT FROM AUTHOR]

The aim – to present the experience of diagnosis, management, and therapy with IL-1 inhibitors in patients with Schnitzler’s syndrome (SchS) according to a multicenter Russian cohort.Materials and methods. In an observational retrospective study for a 10-year period (2012–2022), 17 patients with SchS who were admitted to the hospital or were observed on an outpatient basis, among them 8 women, 9 men, were included in the study. The diagnosis of all corresponded to the Strasbourg diagnostic criteria.Results. The age of patients ranged from 25 to 81 years (Me 53 [46; 56] years). The age at the time of the onset of the disease ranged from 20 to 72 years (Me 46 [39; 54] years), the duration of the disease before diagnosis ranged from 1 to 35 years (Me 6.5 [3; 6] years), in 3 it exceeded 10 years, in the rest it ranged from 1 to 8 years. Infectious and lymphoproliferative diseases, monogenic AIDS (CAPS, TRAPS, HIDS) were excluded from all patients at the prehospital stage. The guiding diagnosis for all was Still’s disease in adults. Clinical manifestations of the disease included: fatigue, lethargy, fatigue, rash and fever in all, skin elements were urticular in all, accompanied by itching in 6 (37.5%). Bone pain had 12 (70.6%), arthralgia – 16 (94.1%), arthritis – 9 (52.9%), myalgia – 7 (41.2%), weight loss in 4 (23.5%). Lymphadenopathy (6), enlarged liver (6), pericarditis (4), angioedema (6), redness and dryness in the eyes (3), sore throat (2), abdominal pain (1), distal polyneuropathy (2), paraesthesia (1), chondritis of the auricles were less common (1). Monoclonal gammopathy was detected in all with a secretion level of 2.9–15.1 g/l: IgMk (n=10 (64.7%)), less often IgMλ (n=2), IgGk (n=2), IgGλ (n=1), IgAλ (n=1). Ben-Jones protein was not detected in any of them. All patients had an increase in the level of ESR, CRP. 16 patients before inclusion in the study received GC (94.1%) with a temporary effect and its escape with dose reduction or cancellation, DMARD – 7, among them methotrexate (5), hydroxychloroquine (2), cyclophosphamide (1), also NSAIDs and antihistamines in all, biological drugs: anti-B-cell the drug rituximab (1), monoclonal AT to IgE – omalizumab in 2 (1 – without effect, 1 – partial effect). 11 patients were prescribed IL-1: canakinumab – 9 (52.9%) subcutaneously once every 8 weeks, anakinra – 4 (23.5%) subcutaneously daily. The duration of taking anakinra, which was prescribed in the test mode, ranged from 1 week to 2.5 months with a further switch to canakinumab in 3. The duration of taking canakinumab at the time of analysis ranged from 7 months to 8 years. Against the background of treatment with IL-1, 10 out of 11 (90.9%) received a complete response from the clinical manifestations of the disease and a decrease in the level of ESR and CRP within a few days. In 1 patient, a partial response was received to the administration of anakinra, and when switching to canakinumab, the effect of treatment was finally lost. 1 patient received IL-6 for 8 months with incomplete effect and transition to IL-1 with positive dynamics. In 1 patient, due to the persistent absence of relapses, the interval between canakinumab injections was increased to 5 months without signs of reactivation, but subsequently, against the background of stress and relapses of the disease, the intervals were reduced to 4 months. A healthy child was born in the same patient on the background of treatment. The tolerability of therapy was satisfactory in all patients, no SAE was noted.Conclusion. SchS is a rare multifactorial/non–monogenic AID that needs to be differentiated from a number of rheumatic diseases and other AIDS. The onset in adulthood, the presence of recurrent urticarial rashes in combination with fever and other manifestations of a systemic inflammatory response are indications for examination for monoclonal secretion. The use of short- or long-acting IL-1 is a highly effective and safe option in the treatment of such patients.

Interleukin 1(IL-1) is an important cytokine, which is involved in the development of many inflammatory diseases. IL-1 inhibitors have become an effective approach in the treatment of these diseases. Anakinra is the first and the most widely used IL-1 inhibitor on the market. Studies have shown satisfactory efficacy in the treatment of some inflammatory dermatoses. This review mainly summarizes applications of anakinra in adult-onset Still's disease, Schnitzler syndrome, hidradenitis suppurativa, pustular psoriasis, Bechet disease and pyoderma gangrenosum.

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 myeloidrelated-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. [ABSTRACT FROM AUTHOR]

Interleukin 1 (IL・1) is an important cytokine, which is involved in the development of many inflammatory diseases・ IL・1 inhibitors have become an effective approach in the treatment of these diseases. Anakinra is the first and the most widely used IL-1 inhibitor on the market. Studies have shown satisfactory efficacy in the treatment of some inflammatory dermatoses・ This review mainly summarizes applications of anakinra in adult-onset Stillf s disease, Schnitzler syndrome, hidraderdtis suppurativa, pustular psoriasis, Bechet disease and pyoderma gangrenosum. [ABSTRACT FROM AUTHOR]

IntroductionThis 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.MethodsOur 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.ResultsFrom 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.ConclusionCurrent 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.

Abstract Objective We aimed to evaluate the efficacy and safety of anti-interleukin-1 therapeutics, including IL-1 antibodies, interleukin-1 receptor antagonists (IL-1 Ras) and IL-1 inhibitors, for knee osteoarthritis (KOA) treatment. Methods Databases (Medline, Embase, Web of Science and CENTRAL) and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) of anti-interleukin-1 therapeutics from inception to August 31, 2022. The outcomes were the mean change in pain and function scores and the risk of adverse effects (AEs). Results In the 12 studies included, anti-interleukin-1 therapeutics were superior to placebo in terms of pain relief (standardized mean difference [SMD] = − 0.38, 95% confidence interval [CI] = − 1.82 to − 0.40, p

Osteoarthritis (OA) is a highly prevalent condition worldwide associated with pain, progressive disability, reduced participation in social activities, and impaired quality of life. Despite its growing burden, the therapeutic options are still limited and almost exclusively addressed to symptoms' management, while no disease-modifying OA drugs able to prevent or retard disease progression are actually available. For these reasons, in the last decades, relevant efforts to find new potential therapeutic targets in OA have been made and a number of existing conventional and biological disease-modifying anti-rheumatic drugs (DMARDs), including hydroxychloroquine (HCQ), methotrexate (MTX), tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 inhibitors, commonly used to treat inflammatory rheumatic diseases, have been repurposed for the treatment of OA and explored also in hand osteoarthritis (HOA). The current narrative review was aimed to provide a comprehensive and updated understanding of the possibilities and the criticisms related to the treatment of HOA with conventional and biological DMARDs. Unfortunately, therapy with conventional and biologic drugs in HOA has not achieved the expected success, despite a rationale for their use exists. Thus, our findings outline the urgent need to enhance the exploration of HOA basic molecular mechanisms to find new potential therapeutic targets, personalized for each patient, and appropriate for the different subsets of HOA and for the different phases of disease. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the efficacy and safety of anti-interleukin-1 therapeutics, including IL-1 antibodies, interleukin-1 receptor antagonists (IL-1 Ras) and IL-1 inhibitors, for knee osteoarthritis (KOA) treatment. Methods: Databases (Medline, Embase, Web of Science and CENTRAL) and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) of anti-interleukin-1 therapeutics from inception to August 31, 2022. The outcomes were the mean change in pain and function scores and the risk of adverse effects (AEs). Results: In the 12 studies included, anti-interleukin-1 therapeutics were superior to placebo in terms of pain relief (standardized mean difference [SMD] = − 0.38, 95% confidence interval [CI] = − 1.82 to − 0.40, p < 0.001, I2 = 77%) and functional improvement (SMD = − 1.11, 95% CI = − 1.82 to − 0.40, p = 0.002, I2 = 96%). The incidence of any AE (risk ratio [RR] = 1.02, 95% CI = 0.88–1.18, p < 0.001, I2 = 76%) was higher following treatment with anti-interleukin-1 therapeutics than placebo, while no significant difference was found in the incidence of serious AEs (SAEs) or discontinuations due to AEs. Subgroup analyses showed that IL-1 antibodies and the IL-1 inhibitor provided pain relief (IL-1 antibodies: SMD = − 0.61, 95% CI = − 0.92 to − 0.31, p < 0.001; IL-1 inhibitor: SMD = − 0.39, 95% CI = − 0.72 to − 0.06, p = 0.02, I2 = 74.0%) and functional improvement (IL-1 antibodies: SMD = − 1.75, 95% CI = − 2.10 to − 1.40, p < 0.001; IL-1 inhibitor: SMD = − 0.28, 95% CI = − 0.83 to 0.27, p = 0.31, I2 = 88%) superior to those of placebo, whereas IL-1 Ras did not. However, the IL-1 inhibitor increased the incidence of any AE (RR = 1.35, 95% CI = 0.92–1.98, p < 0.001, I2 = 85%) but not the risk of SAEs or discontinuations due to AEs. IL-1 antibodies and IL-1 Ras showed no difference in safety compared with placebo. Conclusions: Anti-interleukin-1 therapeutics could relieve OA-related pain and improve function, but is probably associated with an increased risk of adverse events. Specially, IL-1 antibodies and an IL-1 inhibitor could relieve OA-related pain and improve function, whereas IL-1 Ras could not. IL-1 antibodies and IL-1 Ras were relatively safe options, but IL-1 inhibitors were associated with safety concerns. [ABSTRACT FROM AUTHOR]

• Recurrent pericarditis (RP) significantly impacts patients' physical function. • Treatment guidelines recommend initiating therapy for any single episode of acute pericarditis. • In some patients, treatment with biologics is suggested. • Anakinra, rilonacept, and goflikicept are highly promising for RP treatment. Recurrent pericarditis (RP) is defined by the European Society of Cardiology (ESC) as an instance of acute pericarditis (AP) that occurs at least 4–6 weeks after the resolution of a previous episode of the same ailment. To mitigate the risk of RP, it is advised to administer accurate and prolonged pharmacological treatment for both the initial AP and subsequent RP. ESC guidelines recommend commencing treatment for any single episode of AP, including those that contribute to RP, with non-steroidal anti-inflammatory drugs (NSAIDs) in conjunction with colchicine for several months, often followed by gradual tapering. If there is an inadequate response, corticosteroids (CS) may be introduced cautiously. However, in a minority of cases, even when NSAIDs, colchicine, and CS are administered together at the highest recommended dosages, they may prove ineffective. In such instances, treatment with immunosuppressive drugs or biologics is advised. Among biologics, interleukin (IL)-1 inhibitors have been extensively studied, although certain gaps remain. This narrative review delves into the rationale for employing IL-1 inhibitors and presents findings from existing studies regarding their efficacy, tolerability, and safety. Analysis of the literature indicates that there is currently insufficient data to ascertain the true therapeutic role of IL-1 inhibitors in managing and preventing RP. However, theoretically, drugs targeting both IL-1α and IL-1β may offer superior efficacy compared to those solely targeting IL-1β due to the significant involvement of both cytokines in inflammation. Further research is warranted to determine the comparative effectiveness of IL-1α and IL-1β inhibitors. [ABSTRACT FROM AUTHOR]

Paola Galozzi, Sara Bindoli, Andrea Doria, Paolo Sfriso Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, ItalyCorrespondence: Paola Galozzi, Rheumatology Unit, Department of Medicine DIMED, University of Padova, via Giustiniani, 2, Padova, 35128, Italy, Tel +39 049 821 8654, Email paola.galozzi@unipd.itAbstract: Adult-onset Still’s disease (AOSD) is a rare multifactorial autoinflammatory disorder of unknown etiology, characterized by an excessive release of cytokines triggered by dysregulated inflammation and articular and systemic manifestations. The clinical spectrum of AOSD ranges from self-limiting forms with mild symptoms to life-threatening cases and presents clinical and biological similarities with the juvenile form (sJIA). Nowadays, the advances in biologic agents no longer limit the treatment to NSAIDs, glucocorticoids, or conventional synthetic DMARDs. The blockade of IL-1 and IL-6 is effective in the treatment of systemic and articular inflammation of AOSD patients; however, novel compounds with different properties and targets are now available and others are being studied. In this review, starting from the pathogenesis of AOSD, we summarized the current and emerging biological therapies, possible effective agents for achieving AOSD control and remission.Keywords: biologics, AOSD, IL-1 inhibitors, IL-6 inhibitors, small molecules, new treatment

Coronavirus infection can have various degrees of severity and outcomes. In some cases, it causes excessive production of pro-inflammatory cytokines, a so-called cytokine storm, leading to acute respiratory distress syndrome. Unfortunately, the exact pathophysiology and treatment, especially for severe cases of COVID-19, are still uncertain. Results of preliminary studies showed that immunosuppressive therapy, such as interleukin (IL)-6, IL-1, and TNF-α antagonists commonly used in rheumatology, can be considered as treatment options for COVID-19, especially in severe cases. The review focused on the most common and currently studied monoclonal antibody drugs, as well as up-to-date data on the pathogenesis of COVID-19, host immune response against SARS-CoV-2 and its association with cytokine storm. It also covered effects of interleukin (IL)-6, IL-1, and TNF-α blockers on the course of coronavirus infection and outcome in patients treated for the main autoimmune disease and subsequently infected with COVID-19. [ABSTRACT FROM AUTHOR]

Objective: Interleukin-1 inhibitors are effective agents used in colchicine resistance or intolerance during the treatment of familial Mediterranean fever. This study aims to review the characteristics of patients treated with interleukin-1 inhibitors and their long-term follow-up in a large pediatric cohort of familial Mediterranean fever patients. Materials and Methods: The study was conducted in a pediatric rheumatology reference center. The patients treated with interleukin-1 inhibitors for at least 6 months were included and compared to other patients with familial Mediterranean fever. Clinical and laboratory characteristics of the cohort were recorded. Results: Among 542 patients with familial Mediterranean fever, 6.1% (n = 33) were treated with interleukin-1 inhibitors. Colchicine resistance was the reason in 82.8% and renal amyloidosis in 17.2% of the patients. Patients with interleukin-1 inhibitors had earlier disease onset and higher frequencies of acute arthritis, chest pain, and erysipelas-like erythema with pathogenic exon 10 mutations of the MEFV gene (all P < .04). All patients diagnosed with renal amyloidosis also received interleukin-1 inhibitors. Six patients were switched from anakinra to canakinumab or vice versa to control ongoing disease activity. Attack frequency was reduced in all patients. Conclusion: Interleukin-1 inhibitors are used in a relatively small number of pediatric patients with familial Mediterranean fever. Patients presenting with earlier disease onset, acute arthritis, chest pain, and erysipelas-like erythema and carrying pathogenic exon 10 mutations of the MEFV gene may show a higher need for interleukin-1 inhibitors. In pediatric familial Mediterranean fever patients who are resistant to colchicine, interleukin-1 inhibitors seem to be highly effective agents. [ABSTRACT FROM AUTHOR]

Hereditary systemic autoinflammatory diseases (SAIDs) are rare, often severe conditions characterised by mutations in the key regulators of innate immune responses. Dramatic advances in the molecular genetics and next-generation sequencing in the past decade enabled identification of novel mutations that play a pivotal role in the mechanistic pathways of inflammation. Although genetic testing may not always provide straightforward guidance in diagnosis and clinical decision making, through translational research, it sheds light into molecular immunopathogenesis, particularly in IL-1 inflammasome and cytokine signalling pathways. These remarkable insights provided a better understanding of autoinflammatory conditions and their association with the innate and adaptive immune systems, as well as leading to development of cytokine-targetted biologic treatments. Use of targetted therapeutics not only helps control disease flares, reduce acute-phase responses and prevent devastating complications such as amyloidosis, but also improves health-related quality of lives and support patients to pursue almost a normal life. Herein, we discuss the commonest monogenic SAIDs, describe their immunopathology, and summarise the approaches in the management and targetted treatment of these conditions, including presentation of novel data based on a cohort of children with these rare diseases from a single quaternary referral centre in London.

Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome, and the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome are two distinct clinical conditions caused by heterozygous mutations of the PSTPIP1 gene. While skin and joint involvements are shared by both conditions, PAMI is characterized by hepatosplenomegaly, pancytopenia, and growth failure. Kidney involvement is exceptional in PSTPIP1-mediated disorders. The two missense PSTPIP1 variants associated with PAMI syndrome are p.E250K and p.E257K. Long-term treatment with interleukin (IL)-1 inhibitors is effective to control inflammatory manifestations and is usually well-tolerated. We report a case of a patient carrying the PSTPIP1 p.E250K mutation who developed a late-onset kidney involvement despite a long treatment with canakinumab and anakinra. Kidney biopsy showed focal segmental glomerulosclerosis that was treated with tacrolimus (0.1 mg/kg/day in two doses). A literature revision with the aim to assess the proportion and type of kidney involvement in PAMI syndrome revealed that heterogeneous nephropathies may be part of the clinical spectrum. Our study supports the importance of a periodic diagnostic work-up, including kidney laboratory tests and kidney biopsy, in individuals affected with PAMI syndrome. Kidney and liver functions may be impaired regardless of anti-cytokines treatments and additional therapy approaches (i.e., multi-drugs, hematopoietic stem cell transplantation) should be carefully considered.

Objective: To develop French Society of Rheumatology-endorsed recommendations for the management of gout flares.Methods: These evidence-based recommendations were developed by 9 rheumatologists (academic or community-based), 3 general practitioners, 1 cardiologist, 1 nephrologist and 1 patient, using a systematic literature search, one physical meeting to draft recommendations and 2 Delphi rounds to finalize them.Results: A set of 4 overarching principles and 4 recommendations was elaborated. The overarching principles emphasize the importance of patient education, including the need to auto-medicate for gout flares as early as possible, if possible within the first 12h after the onset, according to a pre-defined treatment. Patients must know that gout is a chronic disease, often requiring urate-lowering therapy in addition to flare treatment. Comorbidities and the risk of drug interaction should be screened carefully in every patient as they may contraindicate some anti-inflammatory treatments. Colchicine must be early prescribed at the following dosage: 1mg then 0.5mg one hour later, followed by 0.5mg,2 to 3 times/day over the next days. In case of diarrhea, which is the first symptom of colchicine poisoning, dosage must be reduced. Colchicine dosage must also be reduced in patients with chronic kidney disease or taking drugs, which interfere with its metabolism. Other first-line treatment options are systemic/intra-articular corticosteroids, or non-steroidal anti-inflammatory agents (NSAIDs). IL-1 inhibitors can be considered as a second-line option in case of failure, intolerance or contraindication to colchicine, corticosteroids and NSAIDs. They are contraindicated in cases of infection and neutrophil blood count should be monitored.Conclusion: These recommendations aim to provide strategies for the safe use of anti-inflammatory agents, in order to improve the management of gout flares. [ABSTRACT FROM AUTHOR]

The paper reviews the publications dealing with Schnitzler syndrome, a rare autoinflammatory disease, and describes the authors’ own clinical observation. It describes the first Russian experience in successfully using the interleukin-1 inhibitor canakinumab to treat this disease.

The role of interleukin-1 (IL-1) has been studied in many diseases, ranging from auto-inflammatory diseases to malignancies, and much has been discovered. There are currently four IL-1 inhibitors available, but only two have been approved in Europe: the receptor antagonist anakinra, and the IL-1b selective inhibitor canakinumab. The aim of this paper is to summarize the on- and off-label use of canakinumab (ILARIS).

Abstract Interleukin (IL)-1 inhibitors have been increasingly used for treating autoinflammatory diseases during the last 10 years, but the spectrum of their possible side effects is not yet fully known. Here, we bring physicians’ attention to a new severe complication of IL-1 inhibitors, manifesting as a probable drug reaction with eosinophilia and systemic symptoms (DRESS) in two patients.

The past two decades have brought immense satisfaction to pediatric rheumatologists and families of children with rheumatologic diseases. We have been able to better classify, recognize, and diagnose rheumatologic diseases, but most importantly, the discovery of biologic therapies and their efficacy and relative safety in treating multiple rheumatologic conditions, improving quality of life for the patients we care for. We will review the advances of the past two decades and discuss potential areas for new discoveries. [ABSTRACT FROM AUTHOR]

Cryopyrin-associated periodic syndromes (CAPS) is a rare group of autoinflammatory disorders that includes familial cold autoinflammatory syndrome or FCAS, Muckle - wells syndrome or MWS, and neonatal-onset multisystem inflammatory disease or NOMID. CAPS is caused by a mutation in the NOD-like receptor family, pyrin domain containing 3 (NLRP3) gene. This ultimately leads to increased production of interleukin (IL)-1 ß. IL-1 ß is a biologically active member of the IL-1 family. It is not only a pro-inflammatory cytokine responsible for features such as fever, rash, and arthritis, but is also a major mediator in the central pathways of fatigue. Fatigue is a major component of CAPS and is associated with severely compromised quality of life. In clinical studies, fatigue was measured using functional assessment of chronic illness therapy-fatigue or FACIT-F and short form-36 or SF-36, physical component score instruments. These questionnaires can also be used to monitor improvement of fatigue following initiation of therapy. IL-1 inhibitors block the IL-1 signaling cascade, thereby preventing systemic inflammation in CAPS. The decrease in systemic inflammation is accompanied by improvement in fatigue. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-1 inhibitors have been increasingly used for treating autoinflammatory diseases during the last 10 years, but the spectrum of their possible side effects is not yet fully known. Here, we bring physicians' attention to a new severe complication of IL-1 inhibitors, manifesting as a probable drug reaction with eosinophilia and systemic symptoms (DRESS) in two patients. [ABSTRACT FROM AUTHOR]

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Abstract: Gout is a relatively common inflammatory arthritis that is typically known to occur in middle-aged men. The prevalence of gout appears to be shifting, however, and is increasing in the elderly population. Gout is characterized by severely intense pain and can greatly impact patient quality of life. The study of gout and associated conditions appears to have received research attention in the past, however there is a resurgence in gout interest due to the abundance of novel evidence surrounding its diagnosis, pathophysiology, and treatment. In this review we describe a general overview of gout including its assessment/diagnosis, clinical presentations, predisposing factors, pathophysiology, abortive and prophylactic therapy to control gouty inflammation, and the potential future direction of gout treatment. Perspective: Gout is an underappreciated and extremely painful condition. Over the last 2 years new thought on pathophysiology of gout taking into account the inflammasome and new therapeutic agents have changed management strategies. [Copyright &y& Elsevier]

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood with an incidence of 10-19/100.000 children below the age of 16 years, and it is also one of the major causes of acquired disability and impairment of quality of life in childhood. Early and aggressive control of arthritis is essential to prevent long-term disability. Methotrexate (MTX) provides clinical benefits in JIA with an acceptable profile of toxic effects. Nevertheless, in many cases, inefficacy, especially in patients with polyarticular and systemic-onset form of JIA (SOJIA) or intolerance to MTX, has led investigators to try other therapeutic options. Biologic agents have been designed to target key cytokines implicated in JIA including tumor necrosis factor-a (TNF-α), lnterleukin-1 (IL-1), IL-6 as well as signaling molecules involved in the regulation of T-cell and B-cell lymphocyte responses. Up to now, the U.S. Food and Drug Administration (FDA) has approved three biologic agents for use in moderate to severe polyarticular JIA: etanercept, adalimumab and abatacept. In general, TNF-α inhibitors are more beneficial for children with polyarticular disease, and the biological agents that target IL-1 and IL-6 activity appear to be successful also in treating patients with SOJIA. The T-cell costimulation modulator, abatacept, was shown to be effective for the treatment of patients with moderate to severe polyarticular JIA. Autologous stem cell transplantation has also been used in patients with refractory JIA; however, the procedure carries the risk of treatment-related high morbidity and mortality. The purpose of this review is to summarise the recent advances in the treatment of JIA. [ABSTRACT FROM AUTHOR]

We have developed a quantitative assay for IgG autoantibodies against IL-1α using protein A-Sepharose CL-4B. We examined the autoantibodies in sera from 107 healthy subjects, 151 patients with rheumatoid arthritis (RA), 64 patients with systemic lupus erythematosus (SLE) and 16 patients with systemic sclerosis. The frequency of positive sera for the autoantibodies in patients with RA was 16.6%, which was about three times more frequent (P < 0.01) than that in healthy subjects (5.6%) or that in patients with SLE (4.7%). Only one serum of 16 patients with systemic sclerosis was positive for the autoantibodies. Neutralizing activity of the autoantibodies was demonstrated by murine thymocyte proliferation assay. The concentrations of IgG at 50% inhibition of IL-1α (15 pM) induced thymocyte proliferation ranged between 0.1 and 0.5 mg/ml. A time-course study showed fluctuations of the titres of the autoantibodies in parallel with the disease activity of RA. These results suggest that the anti-IL- 1α autoantibodies present in the sera and possibly some other body fluids may be involved in the regulation of IL-1 activity in vivo. [ABSTRACT FROM AUTHOR]

After trauma, inflammatory, immunological and hormonal changes are well documented. Surgical intervention is a form of programmed trauma. Through the study of surgical patients, changes in early endogenous mediators of inflammation, immune response and tissue repair can be investigated. Here we analysed changes in serum levels of IL-1 inhibitors, IL-1β, IL-6, tumour necrosis factoralpha (TNF-α) and cortisol in patients undergoing elective surgery. C-reactive protein (CRP) was measured as a marker of the acute-phase response. Rises in serum levels of IL-I inhibitors. IL-6 and cortisol were detected as early as 1 h after the intervention. Peak levels were reached between 2 and 5 h. Serum levels of IL-6 and cortisol remained elevated for several days implying a persistent production. Serum levels of IL-1 and TNF did not change after the intervention. CRP levels peaked on day 2. The communication system sustained by endogenous mediators is activated after surgery as shown by selective changes in IL-1 inhibitors, IL-6 and cortisol. These mediators have different kinetics in scrum and IL-6 is not the only early mediator detected. Some IL-1 inhibitors might be involved in the immunological depression observed after major surgery, in the regulation of the inflammatory response or in tissue repair. IL-6 and cortisol seem to act synergistically to activate the acute-phase response. A systemic role for IL-1 and TNF is not evident, even if the possibility that these lymphokines may act locally is not ruled out. [ABSTRACT FROM AUTHOR]

In the panorama of inflammatory arthritis, gout is the most common and studied disease. It is known that hyperuricemia and monosodium urate (MSU) crystal-induced inflammation provoke crystal deposits in joints. However, since hyperuricemia alone is not sufficient to develop gout, molecular-genetic contributions are necessary to better clinically frame the disease. Herein, we review the autoinflammatory features of gout, from clinical challenges and differential diagnosis, to the autoinflammatory mechanisms, providing also emerging therapeutic options available for targeting the main inflammatory pathways involved in gout pathogenesis. This has important implication as treating the autoinflammatory aspects and not only the dysmetabolic side of gout may provide an effective and safer alternative for patients even in the prevention of possible gouty attacks. [ABSTRACT FROM AUTHOR]

The outbreak of Coronavirus disease 2019 (COVID-19) is the current world health concern, presenting a public health dilemma with ascending morbidity and mortality rates exceeding any previous viral spread, without a standard effective treatment yet. SARS-CoV-2 infection is distinguished with multiple epidemiological and pathological features, one of them being the elevated levels of cytokine release, which in turn trigger an aberrant uncontrolled response known as "cytokine storm". This phenomenon contributes to severe acute respiratory distress syndrome (ARDS), leading to pneumonia and respiratory failure, which is considered a major contributor to COVID-19-associated fatality rates. Taking into account that the vast majority of the COVID-19 cases are aggravated by the respiratory and multiorgan failure triggered by the sustained release of cytokines, implementing therapeutics that alleviate or diminish the upregulated inflammatory response would provide a therapeutic advantage to COVID-19 patients. Indeed, dexamethasone, a widely available and inexpensive corticosteroid with anti-inflammatory effects, has shown a great promise in reducing mortality rates in COVID-19 patients. In this review, we have critically compared the clinical impact of several potential therapeutic agents that could block or interfere with the cytokine storm, such as IL-1 inhibitors, IL-6 inhibitors, mast cell targeting agents, and corticosteroids. This work focused on highlighting and contrasting the current success and limitations towards the involvement of these agents in future treatment protocols. Unlabelled Image • Sustained cytokine release is the major hallmark in COVID-19 patients. • Cytokine storm contributes to COVID-19 associated pulmonary damage. • Attenuating cytokine storm offers a promising therapeutic window to COVID-19. • Targeting interleukins, JAK, and mast cell can counteract cytokine storm. • Dexamethasone showed promise as an effective treatment in Covid-19 severe cases. [ABSTRACT FROM AUTHOR]