Safety Of Disease-modifying Antirheumatic Drugs Research Articles

Head-to-head trials in rheumatoid arthritis

Head-to-head studies are important to select the optimal treatment in terms of efficacy and side effect profiles when several drugs are available. This article describes all studies comparing the use of disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA) in head-to-head studies or in which aDMARD was at least included in an active comparison arm. A total of 23studies comparing DMARDs were identified. These included comparisons of Janus kinase (JAK) inhibitors with methotrexate and with adalimumab as well as the oral surveillance study. There are already an exceptionally large number of head-to-head studies in RA, both for comparisons of efficacy and safety of DMARDs. Nevertheless, more such comparative studies are needed, for example to clarify whether adverse events of tofacitinib observed in the oral surveillance study are specific to the JAK1/JAK3 inhibitor or are aclass effect of all JAK inhibitors.

Systematic review and meta-analysis for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

To update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA). We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, 2 independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to csDMARD. Rituximab with and without concomitant csDMARDs showed similar efficacy to other bDMARDs in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. This systematic review provides latest evidence for the 2024 update of the JCR CPG for RA management.

Novel insights into the management of rheumatoid arthritis: one year in review 2023.

New evidence from 2022 slightly changed some perspectives for rheumatoid arthritis (RA) management. Real-world data on the efficacy and safety of disease-modifying anti-rheumatic drugs strengthened the importance of tailoring treatment decisions based on patient characteristics. Moreover, the research of response biomarkers to therapy underlined the need for precision medicine and remote care applications showed an innovative outlook that supports a patient-centred approach. New developments in vaccinations led to the release of updated guidelines and to a consistent improvement in the prevention of vaccine-preventable infections. New literature data also reconsidered drug management in RA-associated interstitial lung disease and pregnancy. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

ObjectivesTo update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for...

Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis

ObjectiveTo perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).MethodsThis is a systematic literature research of 2015–2018 publications on...

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered...

Safety of disease-modifying antirheumatic drugs and biologic agents for rheumatoid arthritis patients in real-life conditions

ObjectiveThe aim of this study was to describe the incidence rate (IR) of adverse drug reactions (ADRs) in daily clinical practice, related to disease-modifying antirheumatic drugs (DMARDs) and biologic agents (BA) in rheumatoid arthritis (RA) patients, and to analyze factors causing discontinuation due to ADRs. MethodsThis was a prospective observational study (October 2010 to October 2011). RA patients who were attended in our hospital taking DMARDs or BA during the study period were included. ADRs were injuries related to these drugs and registered with a software system in routine visits. ADRs could be mild (lowering dosage), moderate (drug discontinuation), or severe (hospital admission). The IR of ADR per 100 patient-years was estimated using survival techniques. Cox regression models (HR; 95% confidence interval) were used to explore factors associated with discontinuation due to ADRs. ResultsIn total, 1202 patients were analyzed, with 158 ADRs (IR = 15.2). Of all ADRs, 80.4% required drug discontinuation (IR = 12.2). Age, less disease and therapy duration, taking corticoids, and combined therapy versus monotherapy (HR = 3; 95% CI: 2.0–4.4) were the factors independently associated to discontinuation due to ADRs. We did not find statistical differences between the different monotherapy regimens. Regarding combinations, Methotrexate + BA had the lowest risk of discontinuation compared to the rest (HR = 0.24; 95% CI: 0.09–0.6). ConclusionsWe have estimated the incidence of ADRs related to DMARDs/BA in real-life conditions. We confirm the role of combined therapy in the development of discontinuations due to ADRs, except for BA + MTX, which did not show an increase of toxicity compared to monotherapy. This combination seems to be safer than others.

SAT0097 Radius: Characterization of physician and patient global assessments in patients with rheumatoid arthritis

BackgroundThe Rheumatoid Arthritis Disease-Modifying Anti-Rheumatic Drug Intervention and Utilization Study 1 (RADIUS 1) is a 5-year observational registry that assessed use, efficacy, and safety of disease-modifying antirheumatic drugs (DMARDs) in...

Anti-rheumatic therapy in patients with rheumatoid arthritis undergoing hemodialysis

Hemodialysis (HD) patients have been increasing recently. Some rheumatoid arthritis (RA) patients need hemodialysis (HD), though the proportion is not high. At present, such patients are almost treated with corticosteroids and/or nonsteroidal anti-inflammatory drugs alone, even if they have a high disease activity that would require disease-modifying anti-rheumatic drug (DMARD) therapy, partly because the safety of DMARDs in RA patients with end-stage renal disease has not been confirmed. Their joint destruction would be inevitable and lead to impaired activities of daily living. As there are no guidelines for the use of DMARDs in HD patients, here I reviewed the previous reports about the treatment of DMARDs including biologics for patients with RA undergoing HD.

Real-world utilization of DMARDs and biologics in rheumatoid arthritis: the RADIUS (Rheumatoid Arthritis Disease-Modifying Anti-Rheumatic Drug Intervention and Utilization Study) study

ABSTRACTObjective: Rheumatoid Arthritis (RA) Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study (RADIUS) is a unique, real-world, prospective, 5-year, observational study of over 10 000 patients with RA. RADIUS provides a snapshot of use patterns, effectiveness, and safety of DMARDs, biologics, and combination therapies used to manage RA in clinical practice.Research design and methods: Patients with RA requiring a new DMARD or biologic (addition or switch) were eligible for the RADIUS study. Two separate patient cohorts were enrolled; RADIUS 1 patients initiated any new therapy at entry, and RADIUS 2 patients initiated etanercept at entry. Patient demographics and disease activity measures were collected at study entry, and baseline characteristics were summarized for various subgroups. Effectiveness, safety, and patterns of use will be tracked for therapies utilized during the 5‐year study.Results: RADIUS 1 enrolled 4959 patients, and RADIUS 2 enrolled 5102 patients, mostly at community private practices (88%). In RADIUS 1, most patients initiated methotrexate (MTX) monotherapy, followed by MTX in combination with a biologic (e.g. infliximab plus MTX) or other DMARD. In RADIUS 2, most patients initiated etanercept in combination with MTX, followed by etanercept monotherapy. When a new therapy was required, physicians tended to add another therapy versus switching therapies. Patients initiating a biologic had a longer duration of RA and more severe disease compared with patients initiating non-biologic therapy.Conclusions: These real-world data provide evidence of the prescribing practices of rheumatologists in 2001–2003. Future analyses will allow evidence-based comparisons of the long-term safety and effectiveness of DMARDs, biologics, and combination therapies to assist physicians in clinical decision-making.

Treatment of inflammatory rheumatic disorders in pregnancy: what are the safest treatment options?

The interaction of pregnancy and the rheumatic diseases varies, ranging from life-threatening conditions such as thromboembolic events and progressive renal disease in some autoimmune disorders, to minor flares of peripheral arthritis in inflammatory rheumatic disease. As a consequence, treatment strategy will vary according to the maternal or fetal compromise expected. All nonsteroidal anti-inflammatory drugs (NSAIDs), including high dose aspirin (acetylsalicylic acid), can cause adverse effects during pregnancy related to the inhibition of prostaglandin synthesis. Prolongation of gestation and labour, constriction of the ductus arteriosus, persistent fetal circulation, impairment of renal function and bleeding are risks of third trimester exposure of pregnant women to all inhibitors of cyclo-oxygenase. Most of these adverse effects can be prevented by discontinuing NSAIDs 8 weeks prior to delivery. Low dose aspirin has not been associated with fetal or neonatal toxicity. Some corticosteroids such as prednisone and prednisolone do not readily cross the placenta and can be safely used during pregnancy as immunosuppressive drugs. Maternal complications related to corticosteroids may occur and close monitoring is therefore mandatory. There is limited information on the safety of disease-modifying antirheumatic drugs including gold, antimalarials, penicillamine (D-penicillamine), sulfasalazine and cyclosporin. Of these agents, sulfasalazine has the best record for tolerability and can be used by pregnant patients. Gold compounds and penicillamine should be discontinued when pregnancy is recognised. Hydroxychloroquine has not been associated with congenital malformations and seems preferable to chloroquine in patients requiring treatment with antimalarials. Use of cyclosporin may be an alternative to other therapy in pregnant patients with severe rheumatic disease. Indications for treatment with colchicine during pregnancy are few, except for familial Mediterranean fever. Azathioprine can be used when the maternal condition requires a cytotoxic drug during the first trimester. Cyclophosphamide, chlorambucil and methotrexate are contraindicated during pregnancy because of their teratogenic potential. Their use may be considered in late pregnancy if the mother has a life-threatening condition.

Optimum Use of Disease-Modifying and Immunosuppressive Antirheumatic Agents During Pregnancy and Lactation

Women with rheumatic diseases frequently need treatment throughout pregnancy and lactation. Physicians must confront the dual challenge of monitoring the possible effects of the underlying maternal disease and the medications on both mother and child. It is essential that the maternal disease is well controlled before, during and after pregnancy to ensure the best possible outcome for the mother and child. Glucocorticoids have been used extensively in pregnant patients with systemic lupus erythematosus and rheumatoid arthritis; there have been no reports of congenital malformations in the exposed infants. There is limited information on the safety of disease-modifying antirheumatic drugs, including hydroxychloroquine, cyclosporin, oral and parenteral gold and sulfasalazine, during pregnancy. However, penicillamine, another disease-modifying antirheumatic drug, is contra-indicated during pregnancy. There is considerable experience with the use of azathioprine during pregnancy if the maternal condition requires a cytotoxic drug. There has been no increased risk of congenital malformations in the exposed infants. The other cytotoxic drugs frequently used in the treatment of rheumatic diseases, chlorambucil, cyclophosphamide and methotrexate, are contraindicated during pregnancy. Glucocorticoids (such as prednisone and methylprednisolone) and hydroxychloroquine are considered to be safe during lactation. Oral and parenteral gold and sulfasalazine can be used with caution during lactation. Penicillamine, cyclosporin and all cytotoxic drugs are contraindicated during lactation.