Tailored first-line biologic and targeted synthetic disease modifying anti-rheumatic drugs therapy in patients with rheumatoid arthritis: 2021 updated ITABIO statements

Objective.To compare rheumatologists’ prescription for first disease modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA) in real-life settings with 2 clinical practice guidelines (CPG), the French Society of Rheumatology/STPR 2004 and EULAR/ESCISIT 2007, and thus assess the gap between practices and guidelines.Method.ESPOIR was a French multicenter cohort study of 813 patients with early arthritis between 2002 and 2005. “Definite” and “probable” RA were defined according to ACR criteria and the level of diagnostic certainty. The objectives were to assess conformity between the observed first-line DMARD prescribed for those patients and the DMARD recommended in the guidelines; and to conduct a mail survey of patients’ usual rheumatologists to investigate the reasons for their nonconformity with guidelines.Results.In total 627 patients with definite or probable RA were identified. Conformity rates were 58% for STPR guidelines and 54% for EULAR guidelines. At 6 months, 83 (34%) patients with early RA did not receive any DMARD. Main determinants associated with conformity to guidelines were disease activity and presence of severity-predictive factors. The main reason leading to a discrepancy between guidelines and daily practice appeared to be diagnostic uncertainty, i.e., the difficulty to reliably assess RA diagnosis as early as the first visits to the rheumatologist.Conclusion.There is a substantial gap between CPG and rheumatologists’ daily practice concerning the first DMARD to prescribe in early RA. This is explained mainly by diagnostic uncertainty. More attention should be paid in future guidelines to the diagnostic difficulties of early RA.

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Reasons for Biologic and Targeted Synthetic Disease-modifying Antirheumatic Drug Cessation and Persistence of Second-line Treatment in a Rheumatoid Arthritis Dataset

The Journal of Rheumatology ◽

10.3899/jrheum.190535 ◽

2019 ◽

Vol 47 (8) ◽

pp. 1174-1181

Author(s):

Peter Youssef ◽

Bruno Marcal ◽

Peter Button ◽

Matt Truman ◽

Paul Bird ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Common Reason ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Start Date ◽

Real World Evidence ◽

Disease Modifying ◽

Noninterventional Study ◽

First Line Treatment

Objective.To provide real-world evidence about the reasons why Australian rheumatologists cease biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) when treating patients with rheumatoid arthritis (RA), and to assess (1) the primary failure rate for first-line treatment, and (2) the persistence on second-line treatments in patients who stopped first-line tumor necrosis factor inhibitors (TNFi).Methods.This is a multicenter retrospective, noninterventional study of patients with RA enrolled in the Australian Optimising Patient outcome in Australian RheumatoLogy (OPAL) dataset with a start date of b/tsDMARD between August 1, 2010, and June 30, 2017. Primary failure was defined as stopping treatment within 6 months of treatment initiation.Results.Data from 7740 patients were analyzed; 6914 patients received first-line b/tsDMARD. First-line treatment was stopped in 3383 (49%) patients; 1263 (37%) were classified as primary failures. The most common reason was “lack of efficacy” (947/2656, 36%). Of the patients who stopped first-line TNFi, 43% (1111/2560) received second-line TNFi, which resulted in the shortest median time to stopping second-line treatment (11 months, 95% CI 9–12) compared with non-TNFi. The longest second-line median treatment duration after first-line TNFi was for patients receiving rituximab (39 months, 95% CI 27–74).Conclusion.A large proportion of patients who stopped first-line TNFi therapy received another TNFi despite evidence for longer treatment persistence on second-line b/tsDMARD with a different mode of action. Lack of efficacy was recorded as the most common reason for making a switch in first-line treatment of patients with RA.

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Pharmacotherapy Options in Rheumatoid Arthritis

Clinical Medicine Insights Arthritis and Musculoskeletal Disorders ◽

10.4137/cmamd.s5558 ◽

2013 ◽

Vol 6 ◽

pp. CMAMD.S5558 ◽

Cited By ~ 39

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.

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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 ◽

10.1136/bmjopen-2017-021447 ◽

2018 ◽

Vol 8 (9) ◽

pp. e021447 ◽

Cited By ~ 8

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.

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Cardiovascular effects of biological versus conventional synthetic disease-modifying antirheumatic drug therapy in treatment-naïve, early rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-217653 ◽

2020 ◽

Vol 79 (11) ◽

pp. 1414-1422 ◽

Cited By ~ 1

Author(s):

Sven Plein ◽

Bara Erhayiem ◽

Graham Fent ◽

Sarah Horton ◽

Raluca Bianca Dumitru ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Early Rheumatoid Arthritis ◽

Antirheumatic Drug ◽

First Line ◽

Dmard Therapy ◽

Link Type ◽

Lv Mass ◽

Disease Modifying ◽

Disease Modifying Antirheumatic Drug

ObjectivesTo determine whether patients with early rheumatoid arthritis (ERA) have cardiovascular disease (CVD) that is modifiable with disease-modifying antirheumatic drug (DMARD) therapy, comparing first-line etanercept (ETN) + methotrexate (MTX) with MTX strategy.MethodsPatients from a phase IV ERA trial randomised to ETN+MTX or MTX strategy±month 6 escalation to ETN+MTX, and with no CVD and maximum one traditional risk factor underwent cardiovascular magnetic resonance (CMR) at baseline, years 1 and 2. Thirty matched controls underwent CMR. Primary outcome measure was aortic distensibility (AD) between controls and ERA, and baseline to year 1 AD change in ERA. Secondary analyses between and within ERA groups performed. Additional outcome measures included left ventricular (LV) mass and myocardial extracellular volume (ECV).ResultsEighty-one patients recruited. In ERA versus controls, respectively, baseline (geometric mean, 95% CI) AD was significantly lower (3.0×10−3 mm Hg−1 (2.7–3.3) vs 4.4×10−3 mm Hg−1 (3.7–5.2), p<0.001); LV mass significantly lower (78.2 g (74.0–82.7), n=81 vs 92.9 g (84.8–101.7), n=30, p<0.01); and ECV increased (27.1% (26.4–27.9), n=78 vs 24.9% (23.8–26.1), n=30, p<0.01). Across all patients, AD improved significantly from baseline to year 1 (3.0×10−3 mm Hg−1 (2.7–3.4) to 3.6×10–3 mm Hg−1 (3.1–4.1), respectively, p<0.01), maintained at year 2. The improvement in AD did not differ between the two treatment arms and disease activity state (Disease Activity Score with 28 joint count)-erythrocyte sedimentation rate-defined responders versus non-responders.ConclusionWe report the first evidence of vascular and myocardial abnormalities in an ERA randomised controlled trial cohort and show improvement with DMARD therapy. The type of DMARD (first-line tumour necrosis factor-inhibitors or MTX) and clinical response to therapy did not affect CVD markers.Trial registration numberISRCTN: ISRCTN89222125; ClinicalTrials.gov: NCT01295151.

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Search of Official Nationwide Database in Japan for Adverse Events Associated with Disease-modifying Antirheumatic Drug Therapies: Focus on Therapies in Combination with Methotrexate Author

10.21203/rs.3.rs-382810/v1 ◽

2021 ◽

Author(s):

Shigeko Inokuma

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Lymphoproliferative Disease ◽

The Other ◽

First Line ◽

Disease Modifying Antirheumatic Drugs ◽

Biologic Drugs ◽

Dmard Therapy ◽

Disease Modifying ◽

Line Drug

Abstract Disease-modifying antirheumatic drugs (DMARDs) are essential for rheumatoid arthritis (RA) therapy, and many synthetic and biologic drugs are available. DMARDs are frequently prescribed in combination with methotrexate (MTX), as it is the first-line drug. The adverse events (AEs) associated with DMARDs have sometimes unfavorable outcomes. Major AEs, particularly therapies in combination with methotrexate, were investigated in this study. A search of the website of the Japanese Pharmaceuticals and Medical Devices Agency for AEs associated with therapies with five DMARDs (MTX, tacrolimus, adalimumab, tocilizumab, and abatacept) reported from 2014 to 2016 was performed. The AEs searched included lymphoproliferative disease (LPD), cytopenia, interstitial pneumonia (IP), infectious pneumonia other than Pneumocystis jirovecii pneumonia (PCP) (i-Pn), and PCP. The number of cases of each AE and its ratio to the total number of cases of all AEs associated with each DMARD therapy were examined. Data were compared among AEs and DMARDs. MTX therapy in combination with other DMARDs was examined for rheumatoid arthritis (RA) cases. On the website, a total of 8874 cases were listed as having AEs associated with therapies with the five DMARDs. For MTX therapy, LPD was the most frequent (1438 cases, 36.4% of all AE cases), followed by cytopenia (10.9%), IP (6.2%), i-Pn (4.1%), and PCP (2.6%). Under therapy with any of the other four DMARDs, i-Pn showed the largest number of cases and the highest ratio (4.2–15.3%); other AEs varied in number and ratio. The proportion of use of MTX in combination with the four DMARDs was highest for PCP (67/71, 94.4%), followed by LPD (50/73, 68.5%), cytopenia (48/73, 65.8%), i-Pn (101/173, 58.4%,), and IP (36/80, 45.0%) (Table 1). In total, including cases reported for MTX therapy, 98.2% (1286/1309) of LPD cases, 88.5% (193/218) of cytopenia cases, 79.8% (174/218) of IP cases, 76.4% (233/305) of i-Pn cases, and 97.6% (165/169) of PCP cases had MTX. In conclusion, LPD was by far the most frequent AE associated with MTX therapy. PCP was strongly associated with the use of MTX in combination with another DMARD. For therapy with any of the other four DMARDs, i-Pn showed the highest ratio.

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

Canadian Journal of Health Technologies ◽

10.51731/cjht.2021.72 ◽

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.

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What are the first-line treatments for rheumatoid arthritis ?

Batna Journal of Medical Sciences (BJMS) ◽

10.48087/bjmstf.2014.1108 ◽

2014 ◽

Vol 1 (1) ◽

pp. 27-33

Author(s):

Assia Haddouche ◽

◽

Samy Slimani ◽

Bilal Bengana ◽

Imen Bencharif ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tight Control ◽

First Line ◽

Disease Modifying Antirheumatic Drugs ◽

Antirheumatic Drugs ◽

Low Disease Activity ◽

New Concepts ◽

European League Against Rheumatism ◽

Disease Modifying ◽

European League

The management of rheumatoid arthritis has not stopped evolving after the advent of new effective therapies and the emergence of new concepts such as tight control, early and aggressive treatment with a target of remission, or at least low disease activity. Strategies to follow are now well codified by the new recommendations of the European League Against Rheumatism (EULAR) 2013, which clearly emphasized that conventional disease-modifying antirheumatic drugs (DMARDs) with methotrexate as a leader are the first-line therapies to use in the treatment of rheumatoid arthritis.

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