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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 -
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 -
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 -
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 -
The Cochrane Database of Systematic... Feb 2011Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates.
OBJECTIVES
To compare the adverse effects of tumor necrosis factor blocker (etanercept, adalimumab, infliximab, golimumab, certolizumab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS).
METHODS
Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework.
MAIN RESULTS
We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95% CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95% CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95% CI 1.06 to 1.64; NNTH = 37, 95% CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706) compared to control.The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95% CI 1.59 to 7.79; NNTH = 17, 95% CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95% CI 1.43 to 2.91; NNTH = 12, 95% CI 8 to 28). Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events.
AUTHORS' CONCLUSIONS
Overall, in the short term biologics were associated with significantly higher rates of total adverse events, withdrawals due to adverse events and TB reactivation. Some biologics had a statistically higher association with certain adverse outcomes compared to control, but there was no consistency across the outcomes so caution is needed in interpreting these results.There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short- and longer-term safety of biologics.
Topics: Antibodies, Monoclonal; Biological Products; Humans; Immunologic Factors; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 21328309
DOI: 10.1002/14651858.CD008794.pub2 -
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 -
BMJ Clinical Evidence Aug 2007Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and... (Review)
Review
INTRODUCTION
Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and swelling, and to improve function. In addition, disease-modifying antirheumatic drugs (DMARDs) may reduce disease progression.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with rheumatoid arthritis who have not previously received any disease-modifying antirheumatic drug treatment? How do different drug treatments compare in people with rheumatoid arthritis who have either not responded to or are intolerant of first-line disease-modifying antirheumatic drugs? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2005 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 62 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adalimumab, anakinra, antimalarial drugs, azathioprine, ciclosporin, corticosteroids, cyclophosphamide, etanercept, infliximab plus methotrexate, leflunomide, methotrexate (alone; or plus sulfasalazine plus hydroxychloroquine), oral gold, parenteral gold, penicillamine, sulfasalazine.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Interleukin 1 Receptor Antagonist Protein; Methotrexate; Treatment Outcome
PubMed: 19454108
DOI: No ID Found -
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 -
Biomedicines Jun 2022The treatment guidelines for hidradenitis suppurativa (HS) vary among different countries, and several biologics and small molecule inhibitors have been tested for... (Review)
Review
BACKGROUND
The treatment guidelines for hidradenitis suppurativa (HS) vary among different countries, and several biologics and small molecule inhibitors have been tested for treating moderate-to-severe HS over the past few years. However, treatment guidelines for HS vary among different countries.
METHODS
A systematic review and meta-analysis was performed to exam the efficacy and serious adverse events (SAEs) of biologics and small-molecule inhibitors in treating moderate-to-severe HS. Binary outcomes were presented as risk ratio (RR) with 95% confidence interval (CI).
RESULTS
We included 16 RCTs with a total of 2076 participants on nine biologics and three small-molecule inhibitors for treating moderate-to-severe HS, including adalimumab, anakinra, apremilast, avacopan, bimekizumab, CJM112, etanercept, guselkumab, IFX-1, INCB054707, infliximab, and MABp1. The meta-analysis revealed only adalimumab (RR 1.77, 95% CI, 1.44-2.17) and bimekizumab (RR 2.25, 95% CI, 1.03-4.92) achieved significant improvement on hidradenitis suppurativa clinical response (HiSCR), and adalimumab was superior to placebo in achieving dermatology life quality index (DLQI) 0/1 (RR 3.97; 95% CI, 1.70-9.28). No increase in SAEs was found for all included active treatments when compared with placebo.
CONCLUSIONS
Adalimumab and bimekizumab are the only two biologics effective in achieving HiSCR with acceptable safety profile, whereas adalimumab is the only biologic effective in achieving DLQI 0/1.
PubMed: 35740325
DOI: 10.3390/biomedicines10061303 -
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