Effectiveness of Tumor Necrosis Factor Inhibitors in Combination with Various csDMARD in the Treatment of Rheumatoid Arthritis: Data from the DREAM Registry

2016 ◽  
Vol 43 (10) ◽  
pp. 1787-1794 ◽  
Author(s):  
Sofie H.M. Manders ◽  
Wietske Kievit ◽  
Tim L.T.A. Jansen ◽  
Jan N. Stolk ◽  
Henk Visser ◽  
...  

Objective.To analyze and compare the effectiveness and drug survival in patients with rheumatoid arthritis, as measured by 28-joint Disease Activity Score (DAS28) and Health Assessment Questionnaire–Disability Index (HAQ-DI), of tumor necrosis factor inhibitor (TNFi) monotherapy, TNFi + leflunomide (LEF), TNFi + sulfasalazine (SSZ), TNFi + other conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and TNFi + methotrexate (MTX) therapy, in daily practice.Methods.Data were collected from the DREAM registry. Patients beginning their first TNFi treatment were included in the study: TNFi monotherapy (n = 320), TNFi + SSZ (n = 103), TNFi + LEF (n = 80), TNFi + other csDMARD (n = 99), TNFi + MTX alone (n = 919), TNFi + MTX + other csDMARD (n = 412). Treatment effectiveness was analyzed using DAS28 and HAQ-DI with linear mixed models and the TNFi drug survival was analyzed using Kaplan-Meier curves and Cox regression. All analyses have been corrected for confounders.Results.The patients who received TNFi + MTX had significantly better DAS28 and HAQ-DI values over time (both p < 0.001) and longer TNFi drug survival than TNFi monotherapy (p < 0.001). TNFi + SSZ and TNFi + other csDMARD had significantly better DAS28 values over time (p = 0.001) and longer drug survival (p = 0.001) versus TNFi monotherapy. TNFi + LEF was not significantly better compared to monotherapy. Adding other csDMARD to the TNFi + MTX combination provided no added value.Conclusion.Preferably, TNFi should be prescribed together with MTX. If this is not possible, we advise the use of other csDMARD.

2015 ◽  
Vol 42 (5) ◽  
pp. 741-748 ◽  
Author(s):  
Jon Thorkell Einarsson ◽  
Pierre Geborek ◽  
Tore Saxne ◽  
Meliha C. Kapetanovic

Objective.To study frequency, possible baseline predictors, timing, and duration of sustained remission [SR; defined as 28-joint Disease Activity Score (DAS28) < 2.6 for at least 6 mos] in patients with established rheumatoid arthritis (RA) treated with different tumor necrosis factor (TNF) inhibitors [etanercept (ETN), infliximab (IFX), adalimumab (ADA)]. In addition, the aim was to compare (head-to-head) the effectiveness of individual drugs in patients receiving their first anti-TNF treatment.Methods.All anti-TNF–treated patients with RA included in the observational South Swedish Arthritis Group register were eligible. We identified the patients’ first SR periods (time between first visit after treatment initiation with DAS28 < 2.6 and subsequent visit with DAS28 ≥ 2.6). Baseline predictors of SR in biologic-naive patients were studied using multivariate regression models. Remission duration and timing of remission start was estimated with Kaplan-Meier curves.Results.Of the 2416 patients included, 382 (15.8%) fulfilled the criteria for SR. Median estimated duration of SR was 5.25 years. Predictors for SR were male sex, low Health Assessment Questionnaire, low DAS28, methotrexate (MTX) treatment, and the calendar year of treatment start. OR for achieving SR within the first 12 months of treatment were 1.86 for ETN (95% CI 1.33–2.61) compared to IFX. HR for 4 years of SR were 1.32 for ETN (95% CI 1.01–1.74) and 1.84 for ADA (95% CI 1.23–2.78), with IFX as the reference drug.Conclusion.SR was uncommon in patients with RA treated with anti-TNF in clinical practice. However, patients remained in SR for a substantial period of time. Concomitant MTX treatment predicts remission. ETN and ADA were more likely in reaching SR.


2021 ◽  
pp. jrheum.201467
Author(s):  
Katerina Chatzidionysiou ◽  
Merete Lund Hetland ◽  
Thomas Frisell ◽  
Daniela Di Giuseppe ◽  
Karin Hellgren ◽  
...  

Objective In Rheumatoid Arthritis (RA), evidence regarding the effectiveness of a second biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in patients whose first ever bDMARD was a non-tumor-necrosis-factor-inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of the second bDMARD (non-TNFi [rituximab, abatacept or tocilizumab, separately] and TNFi) after failure of a non-TNFi bDMARD as first bDMARD. Methods We identified RA patients from the five Nordic biologics registers started treatment with a non-TNFi as first ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed survival-on-drug (at 6 and 12 months), and primary response (at 6 months). Results We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67 and TNFi 427) following failure of a first non-TNFI bDMARD. At 6 and 12 months after start of their second bDMARD, around 70% and 50%, respectively, remained on treatment, and at 6 months less than one third of patients were still on their second bDMARD and had reached low disease activity or remission according to DAS28. For those patients whose second bMDARD was a TNFI, the corresponding proportion was slightly higher (40%). Conclusion The survival-on-drug and primary response of a second bDMARD in RA patients switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.


2010 ◽  
Vol 37 (12) ◽  
pp. 2469-2474 ◽  
Author(s):  
CHRISTOPHER PEASE ◽  
JANET E. POPE ◽  
CARTER THORNE ◽  
BOULOS PAUL HARAOUI ◽  
DON TRUONG ◽  
...  

Objective.We compared variations among Canadian provinces in rheumatoid arthritis (RA) initiating anti-tumor necrosis factor (TNF) therapy.Methods.Data were obtained from the Optimization of Humira trial (OH) and from the Ontario Biologics Research Initiative (OBRI). Baseline characteristics were compared between regions: Ontario (ON), Quebec (QC), and other provinces (OTH). We compared Ontario OH to OBRI patients who were initiating anti-TNF therapy.Results.In 300 OH patients, mean age was 54.8 years (13.3). There were 151 (50.3%) ON patients, 57 from QC (19%), and 92 from OTH (30.7%). Regional differences were seen in the number of disease-modifying antirheumatic drugs (DMARD) ever taken (ON: 3.8 ± 1.4, QC: 3.1 ± 1.1, OTH: 3.3 ± 1.4; p < 0.001); swollen joint count (SJC; ON: 10.9 ± 5.9, QC: 9.0 ± 4.4, OTH: 11.3 ± 5.6; p = 0.033); tender joint count (TJC; ON: 12.2 ± 7.5, QC: 10.3 ± 5.7, OTH: 14.4 ± 7.6; p = 0.003); 28-joint Disease Activity Score (DAS28; ON: 5.8 ± 1.2, QC: 5.6 ± 1.0, OTH: 6.0 ± 1.1; p = 0.076); and Health Assessment Questionnaire (ON: 1.4 ± 0.7, QC: 1.7 ± 0.7, OTH: 1.5 ± 0.7; p = 0.060). DMARD-ever use differed: methotrexate (ON: 94.7%, QC: 93%, OTH: 84.8%; p = 0.025); leflunomide (ON: 74.8%, QC: 21.1%, OTH: 51.1%; p < 0.001); sulfasalazine (ON: 51%, QC: 38.6%, OTH: 25%; p < 0.001); myochrysine (ON: 9.3%, QC: 0%, OTH: 15.2%; p = 0.008); and hydroxychloroquine (ON: 67.5%, QC: 86%, OTH: 66.3%; p = 0.018). In comparison to ON OH patients, 95 OBRI patients initiating first anti-TNF had lower SJC (p = 0.017), TJC (p = 0.008), and DAS28 (p = 0.05).Conclusion.In Quebec, where access to anti-TNF is less restrictive, patients had lower SJC and TJC. ON used more DMARD, especially leflunomide, as mandated by the provincial government. Both provincial funding criteria and prescribing habits may contribute to differences. Canadian rheumatologists may vary in treatment decisions, but patients generally have similar DAS28 when initiating anti-TNF therapy.


2012 ◽  
Vol 39 (8) ◽  
pp. 1546-1554 ◽  
Author(s):  
MARK C. GENOVESE ◽  
MICHAEL SCHIFF ◽  
MICHAEL LUGGEN ◽  
MANUELA LE BARS ◽  
RICHARD ARANDA ◽  
...  

Objective.To evaluate abatacept safety and efficacy over 5 years in patients with rheumatoid arthritis (RA) who had inadequate response to anti-tumor necrosis factor (TNF) therapy in the ATTAIN trial.Methods.Patients completing the 6-month, double-blind (DB) placebo-controlled period were eligible to enter the longterm extension (LTE), where all patients received abatacept every 4 weeks (∼10 mg/kg, according to weight range). Safety, efficacy, physical function, and health-related quality of life were monitored throughout.Results.In total, 317 patients (218 DB abatacept, 99 DB placebo) entered the LTE; 150 (47.3%) completed it. Overall incidences of serious adverse events, infections, serious infections, malignant neoplasms, and autoimmune events did not increase during the LTE versus the DB period. American College of Rheumatology responses with abatacept at Month 6 were maintained over 5 years. At Year 5, among patients who received abatacept for 5 years and had available data, 38/103 (36.9%) achieved low disease activity as defined by the 28-joint Disease Activity Score (DAS28)/C-reactive protein (CRP); 23/103 (22.3%) achieved DAS28/CRP-defined remission. Health Assessment Questionnaire response was achieved by 62.5% of patients remaining on treatment at Year 5; mean improvements from baseline in physical component summary and mental component summary scores were 7.34 and 6.42, respectively. High proportions of patients maintained efficacy and physical function benefits or improved their disease state at each timepoint throughout the LTE, if remaining on abatacept treatment.Conclusion.Safety remained consistent, and abatacept efficacy was maintained from 6 months to 5 years, demonstrating the benefits of switching to abatacept in this difficult-to-treat population of patients with RA previously failing anti-TNF therapy.


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