scholarly journals Conventional Disease-Modifying Antirheumatic Drugs for the Treatment of Rheumatoid Arthritis

2021 ◽  
Vol 1 (5) ◽  
Author(s):  
Shannon Hill ◽  
Nina Frey
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
First Line ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Modifying ◽  
Evidence Based Guidelines

Nine evidence-based guidelines were identified that recommend the use of conventional synthetic disease-modifying antirheumatic drugs as a first-line therapy for patients with rheumatoid arthritis prior to using biologic disease-modifying antirheumatic drugs or Janus kinase inhibitors. Methotrexate monotherapy was the most commonly recommended conventional synthetic disease-modifying antirheumatic drug recommended as first-line therapy by the included guidelines. Eight of the included guidelines recommend combination therapy using multiple conventional synthetic disease-modifying antirheumatic drugs if monotherapy is ineffective and 4 included guidelines recommend the use of glucocorticoids in combination with conventional synthetic disease-modifying antirheumatic drugs.

scholarly journals Pharmacotherapy Options in Rheumatoid Arthritis

2013 ◽  
Vol 6 ◽  
pp. CMAMD.S5558 ◽  
Author(s):  
Pradeep Kumar ◽  
Snehashish Banik
Keyword(s):  
Rheumatoid Arthritis ◽  
Biologic Therapy ◽  
First Line ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Safety Issues ◽  
Disease Modifying ◽  
Disease Modifying Agents ◽  
Term Data

Drugs form the mainstay of therapy in rheumatoid arthritis (RA). Five main classes of drugs are currently used: analgesics, non-steroidal anti-inflammatories (NSAIDs), glucocorticoids, nonbiologic and biologic disease-modifying antirheumatic drugs. Current clinical practice guidelines recommend that clinicians start biologic agents if patients have suboptimal response or intolerant to one or two traditional disease modifying agents (DMARDs). Methotrexate, sulfasalazine, leflunomide and hydroxychloroquine are the commonly used DMARDs. Currently, anti-TNF is the commonly used first line biologic worldwide followed by abatacept and it is usually combined with MTX. There is some evidence that tocilizumab is the most effective biologic as a monotherapy agent. Rituximab is generally not used as a first line biologic therapy due to safety issues but still as effective as anti-TNF. The long term data for the newer oral small molecule biologics such as tofacitinib is not available and hence used only as a last resort.

scholarly journals AB0252 EFFICACY OF A SECOND JANUS KINASE INHIBITOR THAT WAS SWITCHED FOR DIFFICULT-TO-TREAT RA IN CLINICAL PRACTICE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1151.2-1152
Author(s):  
M. Kamiya ◽  
D. Togawa ◽  
S. Mori ◽  
K. Yamazaki
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Retention Rate ◽  
Janus Kinase ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Drug Retention ◽  
Disease Modifying ◽  
Necrosis Factor ◽  
Drug Retention Rate

Background:In clinical practice, when refractory rheumatoid arthritis (RA) is present, of which the definition implies previous use of at least two biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)), the next treatment choice often made is a bDMARD of another class (non-TNFis) [1]. However, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARDs treatment reduces their response [2]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis. The choice of therapeutic agents for refractory RA is increasing, and its efficacy is expected. On the other hand, it is also true that some patients discontinued JAKis at a rate that cannot be overlooked because of insufficient efficacy. Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(3)Objectives:To evaluate real world efficacy of approved JAKis switching in patients with D2T RA who were unable to control their disease activity due to insufficient efficacy despite the sequential use of multiple bDMARDs and JAKis, focusing on the drug retention rate.Methods:In our hospital, RA was diagnosed according to the 1987 or 2010 classification criteria, and when two or more bDMARDs (including both TNFis and non-TNFis) were inadequately effective, it was defined as D2T RA. We retrospectively investigated patients who switched to JAKis for D2T RA. The drug retention rate was investigated by the Kaplan-Meier method, and the difference was tested by the Logrank test.Results:The 1-year retention rate of JAKis for D2T RA was 50.8% in TOF 38 cases [28 women, age average 70.2 years, disease duration average 12.4 years, past bDMARDs use average 3.5 drugs, MTX combination 9 cases, DAS28 ESR average 4.11] and 66.3% in BAR 35 cases [26 cases, 73.0 years old, 14.8 years, 4.17 agents, 9 cases, 3.68], and there was no significant difference (P = 0.30). Among them, there were 17 cases [11 cases, 70.6 years old, 13.5 years, 4.18 drugs, 2 cases, 3.65] of switching between JAKis, all of which were switching from TOF to BAR. The 1-year retention rate was 45.8% [reason for discontinuation: insufficient effect in 3 cases, adverse events in 6 cases], which was not significantly different but tended to be lower than 72.7% [reason for discontinuation: insufficient effect in 1 case, adverse event in 2 cases, patient’s convenience in 1 case] in 16 patients [13 cases, 76.3 years old, 17.1 years, 3.19 drugs, 7 cases, 3.69] who received BAR as the first JAKi for D2T RA patients (P = 0.089).Conclusion:Although the number of cases is small in the retrospective survey, it is suggested that the retention rate of BAR switched to D2T RA may be slightly lower in patients with a history of TOF discontinuation due to insufficient efficacy than in JAKi naive patients. It is expected that the number of new JAKi usage cases will increase in the future, and it is necessary to consider switching between other JAKis in addition to switching from BAR to TOF.References:[1]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77.[2]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25.[3]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344.Disclosure of Interests:None declared

scholarly journals Comparative effectiveness of first-line biological monotherapy use in rheumatoid arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases study on health care administrative databases

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e021447 ◽  
Author(s):  
Ettore Silvagni ◽  
Alessandra Bortoluzzi ◽  
Greta Carrara ◽  
Anna Zanetti ◽  
Marcello Govoni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Record Linkage ◽  
Disease Duration ◽  
Retention Rate ◽  
First Line ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Risk Of Failure ◽  
Disease Modifying

ObjectiveThese analyses aim to comparatively evaluate the persistence on treatment of different biological disease-modifying antirheumatic drugs (bDMARDs) when administered in monotherapy compared with combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA) patients receiving first-line biologics.DesignThis is a retrospective observational study on Administrative Healthcare Databases.MethodsData were extracted from healthcare databases of the Lombardy Region, Italy (2004–2013), as a part of the RECord-linkage On Rheumatic Diseases study, on behalf of the Italian Society for Rheumatology. Analyses included patients with RA starting first-line approved course of bDMARDs and evaluated drug survival by using Cox proportional hazard models. Results are presented as HRs and 95% CI, crude and adjusted for prespecified confounders (age, sex, disease duration, Charlson Comorbidity Index (CCI), previous infections, use of concomitant glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs)).Results4478 patients with RA were included (17.84% monotherapy). Etanercept, adalimumab and infliximab were the most prescribed first-line biologics. bDMARD monotherapy was associated with longer disease duration, higher CCI, lower glucocorticoids and NSAIDs use. Compared with monotherapy, combination associated with a lower risk of failure (adjusted HR 0.79, 95% CI 0.72 to 0.88). Among monotherapies, considering etanercept as reference, adalimumab (1.28, 95% CI 1.03 to 1.59) and infliximab (2.41, 95% CI 1.85 to 3.15) had higher risk of failure. Concomitant methotrexate (0.78, 95% CI 0.70 to 0.87), leflunomide (0.80, 95% CI 0.65 to 0.98) or csDMARD combinations (0.77, 95% CI 0.68 to 0.87) reduced the risk of bDMARD withdrawal.ConclusionAdalimumab and infliximab monotherapies show lower retention rate compared with etanercept. The relatively small number of therapeutic courses different from tumour necrosis factor (TNF) inhibitors makes more difficult to achieve conclusive results with other biologics. Concomitant methotrexate, leflunomide and csDMARDs combination associate with longer survival on bDMARD. Our data confirm the effectiveness of the current practices in the choice of etanercept as first-line anti-TNF monotherapy and strengthen the currently recommended use of bDMARDs in combination with csDMARDs.

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

2020 ◽  
pp. annrheumdis-2019-216655 ◽  
Author(s):  
Josef S Smolen ◽  
Robert B M Landewé ◽  
Johannes W J Bijlsma ◽  
Gerd R Burmester ◽  
Maxime Dougados ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Task Force ◽  
Certolizumab Pegol ◽  
Janus Kinase ◽  
Sustained Remission ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Levels Of Evidence ◽  
Eular Recommendations ◽  
Disease Modifying

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 new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

scholarly journals POS0088 EFFICACY OF JANUS KINASE INHIBITORS FOR DIFFICULT-TO-TREAT RA IN CLINICAL PRACTICE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 252-253
Author(s):  
M. Kamiya ◽  
D. Togawa ◽  
S. Mori ◽  
K. Yamazaki
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitors ◽  
Retention Rate ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Janus Kinase Inhibitors ◽  
Necrosis Factor ◽  
Drug Retention Rate

Background:In 20-30% of rheumatoid arthritis (RA) patients, the first biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)) is ineffective, and among the patients who do respond to therapy, 20% is faced with secondary ineffectiveness within the first 2 years of treatment [1]. In practice, when refractory RA is present, of which the definition implies previous use of at least two bDMARDs (generally TNFis), the next treatment choice often made is a bDMARD of another class (non-TNFis) [2]. On the other hand, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARD treatment reduces their response [3]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis.Objectives:Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(4). We evaluated real world efficacy of approved JAKis and factors that may help to continue them in patients with D2T RA.Methods:Patients who had inadequate response to two or more bDMARDs (including both TNFis and non-TNFis) at our hospital by December 2019 were defined as D2T RA, and patients who switched to JAKis were retrospectively investigated. The drug retention rate was determined by Kaplan-Meier method, and the difference was tested by Logrank test. Multiple regression analysis was used as the statistical method to predict continuation of JAKis for more than 1 year, with patient background (age, gender, during the disease, number of bDMARDs used, with or without methotrexate and/or glucocorticoids, disease activity score assessing 28 joints using erythrocyte sedimentation rate’ presence of rheumatoid factor/anti-CCP antibody, matrix metalloproteinase 3 value, Health Assessment Questionnaire disability index) at the time of initiation as an explanatory variable.Results:A total of 915 bDMARDs had been administered to 394 RA patients. The retention rate of bDMARDs and the number of bDMARDs used were 89.3% and 1.48 bDMARDs at 1 year, 67.7% and 2.27 bDMARDs at 5 years, and 52.0% and 3.15 bDMARDs at 10 years, respectively. The retention rate of JAKis at 1 year was 60.2% in 65 patients with tofacitinib (TOF) and 67.2% in 70 patients with baricitinib (BAR) (P=0.38). Among them, the drug retention rate in D2T RA patients was 50.8% in 38 TOF patients and 66.3% in 35 BAR patients with no significant difference (P=0.30). There were no patient background factors that significantly predicted continuation at 1 year for any JAKis.Conclusion:Despite the limited number of patients and the retrospective nature of the study, TOF and BAR were shown to be effective options for D2T RA, regardless of patient background such as disease activity or number of bDMARDs used. Other JAKis and switches between JAKis need to be investigated in the future.References:[1]Schaeverbeke T, Truchetet ME, Kostine M et al. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology 2016;55:210_20.[2]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77.[3]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25.[4]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344.Disclosure of Interests:None declared

scholarly journals AB0712 THE INCIDENCE OF SARS-СOV-2 INFECTION IN PATIENTS WITH RHEUMATIC DISEASES ON THERAPY BIOLOGICAL DISEASE MODIFYING ANTIRHEUMATIC DRUGS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1387.3-1388
Author(s):  
A. Dadalova ◽  
E. Vasilenko ◽  
R. Samigullina ◽  
V. Mazurov
Keyword(s):  
Rheumatic Diseases ◽  
Interleukin 6 ◽  
Kinase Inhibitors ◽  
Biological Therapy ◽  
Janus Kinase ◽  
Interleukin 17 ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Tnf Α ◽  
Disease Modifying

Background:At the moment, a highly relevant issue is the course of SARS-CoV-2 infection in patients with rheumatic pathology, especially, those receiving therapy with biological disease modifying antirheumatic drugs.Objectives:of the current study to assess the prevalence and course of SARS-CoV-2 infection in patients receiving various biological disease modifying antirheumatic drugs.Methods:to assess the severity of the course of SARS-CoV-2, discharged epicrisis from hospitals or the conclusion of computed tomography were used. The average age of the patients ranged from 41.4 + 11.6 years. In the evaluated sample, 47 patients (49.47%) were males. Among the infected of SARS-CoV-2 were patients with rheumatoid arthritis - 45 (47.4%), spondyloarthritis - 39 (41.1%), systemic connective tissue diseases - 11 (11.5%).Results:Since March 2020, among the 1319 patients with rheumatic diseases observed at the St. Petersburg Center of therapy biological disease modifying antirheumatic drugs, 95 patients (7,2%) had SARS-CoV-2 infection. In 57,9% (55 patients) there was a mild course of infection, in 35,8% of cases (34 patients) - a moderate course, in 6,3% (6 patients) - a severe course. Inpatient treatment was received by 29,5% (28 patients). A favorable outcome was noted in 95.8%, and a lethal outcome in 4,2%. The use of interleukin-6 inhibitors was required in 2,1% of patients (2) due to the development of a cytokine storm. The structure of the received biological therapy in the severity of the course is shown in Table 1.Table 1.The structure of the received biological therapy in the severity of the course SARS-CoV-2 infectionMild courseCT-1 (<25%)CT-2 (25-50%)CT-3 (50-75%)CT-4 (>75%)TNF-α inhibitors, n (%)30 (31,6)11 (11,6)7 (7,3)3 (3,2)0 (0,0)anti B-cell therapy (rituximab), n (%)2 (2,1)1 (1,1)2 (2,1)1 (1,1)2 (2,1)Abatacept, n (%)3 (3.2)0 (0,0)2 (2,1)0 (0,0)0 (0,0)Janus kinase inhibitors, n (%)5 (5,3)1 (1,1)1 (1,1)0 (0,0)0 (0,0)Interleukin-6 inhibitors, n (%)6 (6,3)0 (0,0)0 (0,0)0 (0,0)0 (0,0)Interleukin-17 inhibitors, n (%)8 (8,4) 2 (2,1) 2 (2,1)0 (0,0)0 (0,0)Other, n (%)1 (1,1)4 (4,2)1 (1,1)0 (0,0)0 (0,0)Among 95 infected patients, who were observed in the center, 51 received therapy with TNF-α inhibitors (8.5% of the total number of patients receiving therapy), 8 - rituximab therapy (2.7%), 5 - abatacept (6.3%), 7 - Janus kinase inhibitors (0.9%), 6 – interleukin-6 inhibitors (9.2), 12 - interleukin -17 inhibitors (14.1%), 6 patients treated with other drugs (10%).Conclusion:Taking into account the SARS-CoV-2 pandemic, further study of the course of infection in patients with rheumatic diseases, including those receiving biological therapy, is required. More information is also needed on the safety and efficacy of vaccination in this patient population.Disclosure of Interests:None declared

scholarly journals Treatment Patterns and Pharmacoutilization in Patients Affected by Rheumatoid Arthritis in Italian Settings

2021 ◽  
Vol 18 (11) ◽  
pp. 5679
Author(s):  
Valentina Perrone ◽  
Serena Losi ◽  
Veronica Rogai ◽  
Silvia Antonelli ◽  
Walid Fakhouri ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Patterns ◽  
Administrative Databases ◽  
First Line ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Synthetic Dmards

This study aimed to evaluate the treatment patterns and pharmacoutilization of patients with rheumatoid arthritis (RA) in real-world settings in Italy. This retrospective observational analysis was based on administrative databases of selected Italian entities. All adult patients with RA diagnosis confirmed by ≥1 discharge diagnosis of RA (ICD-9-CM code = 714.0) or an active exemption code (006.714.0) were enrolled in 2019. Two cohorts were created: one included patients prescribed baricitinib, the other those prescribed biological disease-modifying antirheumatic drugs (bDMARDs). Overall, 47,711 RA patients were identified, most of them without DMARD prescription. As a first-line prescription, 43.2% of patients were prescribed conventional synthetic DMARDs (csDMARDs), 5.2% bDMARDs and 0.3% baricitinib. In 2019, 82.6% of csDMARD users continued with the same DMARD category, 15.9% had a bDMARD, while 1.5% had baricitinib as second-line therapy. Overall, 445 patients used baricitinib during 2019. During follow-up, baricitinib was prescribed as monotherapy to 31% of patients, as cotreatment with csDMARDs and corticosteroids to 27% of patients, with corticosteroids to 28% of patients and with csDMARDs to 14% of patients. In line with previous findings, a trend of bDMARD undertreatment was observed. The treatment patterns of baricitinib patients could help to better characterize patients eligible for new therapeutic options that will be available in the future.

scholarly journals Janus Kinase Inhibitors for the Treatment of Rheumatoid Arthritis

2017 ◽  
Vol 52 (10) ◽  
pp. 667-668 ◽  
Author(s):  
Senir Turan ◽  
Scot Walker
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Reactions ◽  
Kinase Inhibitors ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Oral Drugs ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Janus Kinase Inhibitors ◽  
Skin Conditions

Rheumatoid arthritis (RA) is a disease where the immune system attacks the linings of the joints, resulting in joint pain, stiffness, swelling, and destruction. Although many products are available for the treatment of RA, limitations such as adverse reactions and tolerance greatly affect adherence. Many of the current biologic disease-modifying antirheumatic drugs on the market are injectables, leaving a void to be filled for a product that can be taken orally. The most advanced of these approaches, the Janus kinase (JAK) inhibitors, are oral drugs that have not only made a breakthrough in RA, but also other skin conditions.

Sign in / Sign up

Export Citation Format

Share Document