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RMD Open 2019To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League Against Rheumatism treatment recommendations.
METHODS
The MEDLINE, EMBASE and Cochrane databases were searched for case-control/prospective cohort studies, randomised controlled trials (RCTs) and systematic reviews.
RESULTS
Current evidence in primary SjS patients fulfilling the 2002 criteria is based on the data from 9 RCTs, 18 prospective cohort studies and 5 case-control studies. Two Cochrane systematic literature reviews (SLRs) have reported that topical treatments for dry mouth and dry eye are safe and effective. Ocular cyclosporine A was safe and effective in two RCTs including 1039 patients with dry eye syndrome. Two Cochrane SLRs on serum tear drops and plugs showed inconsistency in possible benefits, both for symptoms and objective measures. Five RCTs reported significant improvements in oral dryness and salivary flow rates for pilocarpine and cevimeline. An RCT showed no significant placebo-differences for hydroxychloroquine 400 mg/day for the primary outcome (visual analogue scale (VAS) composite of dryness, fatigue and pain). We identified seven RCTs carried out in primary SjS patients. RCTs using infliximab, anakinra and baminercept found no placebo-differences for the primary outcomes. The two largest RCTs randomised 255 patients to receive rituximab or placebo and reported no significant results in the primary outcome (VAS composite), while prospective studies suggested efficacy in systemic disease.
CONCLUSION
The current evidence supporting the use of the main topical therapeutic options of primary SjS is solid, while limited data from RCTs are available to guide systemic therapies.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Humans; Sjogren's Syndrome; Treatment Outcome
PubMed: 31749986
DOI: 10.1136/rmdopen-2019-001064 -
Frontiers in Immunology 2022The cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be...
BACKGROUND
The cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be efficacious in treating numerous IL-1-mediated pathologies. Currently, three IL-1 blockers are approved, namely anakinra, canakinumab and rilonacept, and two additional ones are expected to receive approval, namely gevokizumab and bermekimab. However, there is no systematic review on the safety and efficacy of these biologics in treating immune-mediated diseases.
OBJECTIVE
To evaluate safety and efficacy of anakinra, canakinumab, rilonacept, gevokizumab, and bermekimab for the treatment of immune-mediated disorders compared to placebo, standard-of-care treatment or other biologics.
METHODS
The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 1 January 1984 and 31 December 2020 focusing on immune-mediated disorders. Our PubMed literature search identified 7363 articles. After screening titles and abstracts for the inclusion and exclusion criteria and assessing full texts, 75 articles were included in a narrative synthesis.
RESULTS
Anakinra was both efficacious and safe in treating cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), gout, macrophage activation syndrome, recurrent pericarditis, rheumatoid arthritis (RA), and systemic juvenile idiopathic arthritis (sJIA). Conversely, anakinra failed to show efficacy in graft-versus-host disease, Sjögren's syndrome, and type 1 diabetes mellitus (T1DM). Canakinumab showed efficacy in treating CAPS, FMF, gout, hyper-IgD syndrome, RA, Schnitzler's syndrome, sJIA, and TNF receptor-associated periodic syndrome. However, use of canakinumab in the treatment of adult-onset Still's disease and T1DM revealed negative results. Rilonacept was efficacious and safe for the treatment of CAPS, FMF, recurrent pericarditis, and sJIA. Contrarily, Rilonacept did not reach superiority compared to placebo in the treatment of T1DM. Gevokizumab showed mixed results in treating Behçet's disease-associated uveitis and no benefit when assessed in T1DM. Bermekimab achieved promising results in the treatment of hidradenitis suppurativa.
CONCLUSIONS
This systematic review of IL-1-targeting biologics summarizes the current state of research, safety, and clinical efficacy of anakinra, bermekimab, canakinumab, gevokizumab, and rilonacept in treating immune-mediated disorders.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021228547.
Topics: Arthritis, Juvenile; Arthritis, Rheumatoid; Biological Products; Cryopyrin-Associated Periodic Syndromes; Diabetes Mellitus, Type 1; Familial Mediterranean Fever; Gout; Humans; Immune System Diseases; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Pericarditis
PubMed: 35874710
DOI: 10.3389/fimmu.2022.888392 -
Rheumatology (Oxford, England) Nov 2023To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.
OBJECTIVES
To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.
METHODS
A protocolized systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Three databases were searched for reports on treatment strategies for VEXAS. Data from the included publications was extracted and a narrative synthesis was performed. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analysed.
RESULTS
We identified 36 publications with a total of 116 patients; 113 (98.3%) were male. The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), Janus kinase inhibitors (JAKi) (CR 11/33, 33%; PR 9/33, 27.3%), tocilizumab (CR 3/15, 20%; PR 6/15, 40%), allogeneic stem cell transplantation (CR 6/7, 85.7%; one patient died), anakinra (CR 4/5, 80%; NR 1/5, 20%), canakinumab (CR 1/2, 50%; PR 1/2, 50%) and glucocorticoid monotherapy (CR 1/6, 16.7%; PR 4/6, 66.7%). Individual reports were available for TNF inhibitors, rituximab and MTX. Data on adverse events were available for 67 patients (67/116, 57.8%) and included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (6/67, 8.9%), cytopenias (4/67, 5.9%), and acute (4/67, 5.9%) and chronic graft-vs-host-disease (2/67, 2.9%).
CONCLUSION
Current data on VEXAS treatment are limited and inhomogeneous. Treatment decisions should be individualized. For the devolvement of treatment algorithms clinical trials are needed. Adverse events remain a challenge, especially an elevated risk for venous thromboembolism associated to JAKi treatment should be carefully considered.
Topics: Humans; Male; Female; Algorithms; Azacitidine; Bronchiolitis Obliterans Syndrome; Databases, Factual; Janus Kinase Inhibitors; Mutation
PubMed: 37233149
DOI: 10.1093/rheumatology/kead240 -
Annals of the Rheumatic Diseases May 2016A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy...
A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease.
Topics: Abnormalities, Drug-Induced; Antirheumatic Agents; Biological Products; Delphi Technique; Female; Humans; Infant, Newborn; Lactation; Maternal-Fetal Exchange; Preconception Care; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Rheumatic Diseases
PubMed: 26888948
DOI: 10.1136/annrheumdis-2015-208840 -
Cureus Nov 2022Interleukin 1 (IL-1) has been indicated as a mediator of recurrent pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing interleukin 1... (Review)
Review
Interleukin 1 (IL-1) has been indicated as a mediator of recurrent pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing interleukin 1 alpha (IL-1α) and interleukin 1 beta (IL-1β), has demonstrated promising results in a phase II study in recurrent or refractory pericarditis. Anakinra is a recombinant inhibitor of the IL-1 receptor with a demonstrated reduction in the incidence of recurrent pericarditis. Definite pharmacological management of pericarditis is key to preventing recurrences, mostly treatment options for recurrent pericarditis refractory to conventional drugs. Here we critically discuss the existing therapy options for recurrent pericarditis, with a focus on new pharmacological approaches: rilonacept and anakinra. A systematic search was conducted across online databases such as PubMed, Cochrane, Google Scholar, ScienceDirect, CINAHL, Scopus, and Embase to obtain clinical trials that assess the effectiveness of anti-interleukin 1 therapy such as anakinra and rilonacept in the management of recurrent pericarditis. Our study concluded that anti-interleukin 1 therapy significantly improved both the quality of life and the clinical outcomes of the study population. These outcomes were most prominent with the use of rilonacept and anakinra in the trial treatment. Rilonacept and anakinra are valuable options in case of recurrent pericarditis refractory to conventional drugs.
PubMed: 36505131
DOI: 10.7759/cureus.31226 -
Clinical and Experimental Rheumatology May 2022Due to the rarity of relapsing polychondritis (RP), no randomised clinical trial has been conducted to date and treatment remains empirical. We performed a systematic... (Review)
Review
OBJECTIVES
Due to the rarity of relapsing polychondritis (RP), no randomised clinical trial has been conducted to date and treatment remains empirical. We performed a systematic literature review to assess the efficacy of the main conventional immunosuppressants and biotherapies used in RP.
METHODS
We searched MEDLINE for original articles without language restriction. Abstracts from American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) were also considered for inclusion. Observational studies and clinical trials reporting on the efficacy of conventional immunosuppressants and biotherapies in adult patients with RP were selected and pooled response rates for each treatment were computed.
RESULTS
Of 304 articles and abstracts identified, 31 underwent full-text review, and 11 were included. The studies involved a total of 177 patients, exposed to a total of 247 lines of treatments. The main treatments studied (by number of lines) were: TNF inhibitors (TNFi), n=92; methotrexate (MTX), n=38; tocilizumab (TCZ), n=26; anakinra (ANA), n=21; rituximab (RTX), n=16; abatacept (ABT), n=14; cyclophosphamide (CYC), n=14; azathioprine (AZA), n=13. The pooled response rates across studies were: 72% [95% CI: 42-95] for ABT, 66% [95% CI: 49-82] for TCZ, 64% [95% CI: 53-74] for TNFi, 56% [95% CI: 37-73] for MTX, 47% [95% CI: 26-68] for ANA, 43% [95% CI: 20-68] for RTX. Based on more limited data, response rates for AZA and CYC ranged from 38 to 100% and from 25 to 100%, respectively.
CONCLUSIONS
In this systematic review of available evidence regarding the treatment of relapsing polychondritis, ABT, TCZ and TNFi were the drugs associated with the best outcomes. ABT efficacy must be interpreted in light of the small number of patients treated. While MTX had slightly less efficacy, it is one of the drugs for which data are the most robust.
Topics: Abatacept; Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Immunosuppressive Agents; Methotrexate; Polychondritis, Relapsing; Rituximab; Tumor Necrosis Factor Inhibitors
PubMed: 35238756
DOI: 10.55563/clinexprheumatol/h9gq1o -
Seminars in Arthritis and Rheumatism Feb 2021Calcium pyrophosphate crystal deposition disease (CPPD) is a common cause of acute and chronic arthritis, especially in the elderly population. There is a paucity of... (Review)
Review
OBJECTIVE
Calcium pyrophosphate crystal deposition disease (CPPD) is a common cause of acute and chronic arthritis, especially in the elderly population. There is a paucity of data regarding the management of CPPD disease, which is currently based on expert opinion and evidence derived from the treatment of gout. We conducted a systematic literature review in order to identify the available treatment options for CPPD, and describe their efficacy and safety.
MATERIAL AND METHODS
Online databases were searched from inception to May of 2020 using the search terms: (CPPD [Title/Abstract] OR CPDD [Title/Abstract] OR calcium pyrophosphate [Title/Abstract] OR chondrocalcinosis [Title/Abstract]) AND (treatment [Title/Abstract] OR management [Title/Abstract] OR therapy [Title/Abstract]). Articles evaluating the use of specific treatment agents for CPPD were eligible for inclusion. Case reports were excluded.
RESULTS
A total of 22 eligible studies and 403 unique patients were selected. We identified only 3 randomized, double-blind, controlled trials (RCTs) evaluating the use of methotrexate, hydroxychloroquine, and magnesium carbonate in CPPD, and these therapeutic options, with the exception of methotrexate, have shown efficacy and reduction of pain intensity. Further, 10 case series and 9 cohort studies were included. Intramuscular and intra-articular glucocorticoids, ACTH, as well as the biologic agents anakinra and tocilizumab appear to be efficacious in CPPD. Intra-articular injections of glycosaminoglycan polysulphate, hyaluronic acid and yttrium, as well as synovial membrane destruction by laser irradiation were associated with symptomatic improvement. Due to significant study heterogenicity, direct comparison between studies was not possible.
CONCLUSION
There are a limited number of studies evaluating the treatment of CPPD. High quality evidence is rather limited, while commonly administered agents such as NSAIDs, colchicine and corticosteroids have not been evaluated by RCTs. The need for high quality evidence supporting specific treatment modalities is urgent for this common yet neglected form of arthritis.
Topics: Aged; Calcium Pyrophosphate; Chondrocalcinosis; Colchicine; Gout; Humans; Methotrexate; Randomized Controlled Trials as Topic
PubMed: 33360232
DOI: 10.1016/j.semarthrit.2020.10.005 -
European Journal of Medical Research Feb 2023At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the treatment of COVID-19 patients with elevated soluble urokinase plasminogen activator receptor (suPAR). However, the role of Anakinra in COVID-19 remains unanswered, especially in patients receiving different forms of respiratory support. Therefore, the objective of this systematic review is to assess the safety and effects of Anakinra compared to placebo or standard care alone on clinical outcomes in adult hospitalized patients with SARS-CoV-2 infection.
METHODS
We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, medRxiv, and the Cochrane Central Register of Controlled Trials (CCSR)) and the WHO COVID-19 Global literature on coronavirus disease database to identify completed and ongoing studies from inception of each database to December 13, 2021. Since then, we monitored new published studies weekly up to June 30, 2022 using the CCSR. We included RCTs comparing treatment with Anakinra to placebo or standard care alone in adult hospitalized patients with SARS-CoV-2 infection.
RESULTS
We included five RCTs with 1,627 patients (n = 888, n = 739, mean age 59.63 years, 64% male). Random-effects meta-analysis was used to pool data. We found that Anakinra makes little or no difference to all-cause mortality at up to day 28 compared to placebo or standard care alone (RR 0.96, 95% CI 0.64-1.45; RD 9 fewer per 1000, 95% CI 84 fewer to 104 more; 4 studies, 1593 participants; I = 49%; low certainty of evidence).
CONCLUSIONS
Anakinra has no effect on adult hospitalized patients with SARS-CoV-2 infection regarding mortality, clinical improvement and worsening as well as on safety outcomes compared to placebo or standard care alone.
TRIAL REGISTRATION
PROSPERO Registration Number: CRD42021257552.
Topics: Adult; Humans; Male; Middle Aged; Female; COVID-19; Interleukin 1 Receptor Antagonist Protein; SARS-CoV-2
PubMed: 36841793
DOI: 10.1186/s40001-023-01072-z -
Medical Sciences (Basel, Switzerland) Dec 2022Heart failure (HF) has become increasingly difficult to manage given its increasing incidence. Despite the availability of novel treatment target relieving inhibition... (Meta-Analysis)
Meta-Analysis Review
Heart failure (HF) has become increasingly difficult to manage given its increasing incidence. Despite the availability of novel treatment target relieving inhibition and congestions for neurohormonal activation, heart failure is one of leading health conditions associated with high hospitalization and readmission rates, resulting in poor quality of life. In light of this, this article serves to demonstrate the effect of anakinra as one of the treatment paradigms for HF to explore the need for advanced novel interventions. We conducted a search in five electronic databases, including , , , , and , for RCTs (randomized controlled trials) evaluating the effects of anakinra against placebo in HF. Meta-analysis was performed using RevMan version 5.4. Eight RCTs were obtained and included for analysis in this study. The results demonstrate that anakinra significantly reduces the levels of CRP (C-reactive protein), with significant difference between anakinra- and placebo-treated groups. Analyses also show that CRP failed to cause an improvement in peak oxygen consumption and ventilatory efficiency. Additionally, the treatment-related adverse events were insignificant. Some considerable limitations are that the same set of researchers were involved in most of the studies; hence, more independent studies need to be encouraged. Anakinra was associated with a reduction in CRP levels, indicating some anti-inflammatory effects but no effect on function, exercise capacity, and adverse effects.
Topics: Humans; Heart Failure; Hospitalization; Interleukin 1 Receptor Antagonist Protein; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36649041
DOI: 10.3390/medsci11010004 -
Cureus Oct 2022Inflammation of the pericardium is referred to as pericarditis, which can cause sharp chest pain and has a high chance of recurrence even after treatment. This review... (Review)
Review
Inflammation of the pericardium is referred to as pericarditis, which can cause sharp chest pain and has a high chance of recurrence even after treatment. This review will explore anakinra, which is an interleukin-1 receptor antagonist, as a potential new treatment for pericarditis. The systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by searching PubMed and GoogleScholar from the years 2012 to 2022. After applying inclusion and exclusion criteria, thorough screening, and quality appraisal, a total of eleven studies were included in the review; eight case reports and three clinical trials. All studies showed that 100 mg/day of anakinra caused a remarkable improvement in patient outcomes. In addition, the pericarditis resolved quicker and had a lower chance of recurrence in comparison to conventional therapy.
PubMed: 36212270
DOI: 10.7759/cureus.29862