Validation of the Methotrexate‐First Strategy in Patients With Early, Poor‐Prognosis Rheumatoid Arthritis: Results From a Two‐Year Randomized, Double‐Blind Trial

O'Dell, James Robert; Curtis, Jeffrey R.; Mikuls, Ted R.; Cofield, Stacey S.; Bridges, S. Louis; Ranganath, Veena K.; Moreland, Larry W.

doi:10.1002/art.38012

Cited by 75 publications

(65 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…O'Dell et al 60 presented very similar results to those provided in Moreland et al 58 It was reported that no statistically significant difference was observed between the percentage of patients in each treatment modality (immediate combination treatment vs. step-up treatment) who discontinued treatment by week 24 (p = 0.84). Nor was any statistically significant difference observed between the percentage of patients in each treatment modality (immediate combination treatment vs. patients who stepped up treatment at week 24 vs. patients who remained on MTX monotherapy at week 24) who discontinued treatment between weeks 24 and 102 (p = 0.86).…”

Section: Assessment Of Cost-effectivenesssupporting

confidence: 59%

“…Eleven trials [26][27][28][29][30][31][32][33][34][35][36][38][39][40][41][42][43][44][45][46][47][48][49]51,[54][55][56][57][58][59][60]62,[64][65][66][67] examined an early RA population (defined as disease duration of < 3 years; see Chapter 4, Inclusion and exclusion criteria) [i.e. BehandelStrategieën in Reumatoïde Artritis (BeSt), 26- 55 the TreaTing to Twin Targets (T-4) study, 56,57 the Treatment of Early Aggressive Rheumatoid arthritis (TEAR) trial [58][59][60] and the early rheumatoid arthritis treated with tocilizumab, methotrexate or their combination (U-Act-Early) trial 62 ], three trials 9,50,52,53 examined an established RA population [i.e. British Rheumatoid Outcome Study Group (BROSG) trial, 9 Fransen et al 50 and the Optimisation of Adalimumab study 52,53 ] and two trials 61,63 examined populations that i...…”

Section: Assessment Of Clinical Effectivenessmentioning

confidence: 99%

“…the TIght COntrol for RA (TICORA) trial 61 examined patients with a disease duration of < 5 years and van Hulst et al 63 reported including both newly diagnosed patients and those with established disease (and did not report on the findings for these patients separately at all)]. Six studies 50 52,53 the T-4 study 56,57 and the TEAR trial [58][59][60] ) and six studies 26- 54 and the TEAR trial [58][59][60] ). Two studies 9,35,36,67 made other comparisons which did not seem to fit with any of the above comparisons (i.e.…”

Section: Assessment Of Clinical Effectivenessmentioning

confidence: 99%

“…If at any time point the DAS was ≥ 1.6, the last effective treatment was restarted. In case of intolerance to a DMARD, the highest tolerated dose was used and, if the DAS was ≥ 1.6 at the next visit, the patient went on to the next step TEAR [58][59][60] A DAS28-ESR of ≥ 3. 1.…”

Section: Disease-modifying Antirheumatic Drug and Biologic Combinationsmentioning

confidence: 99%

“…The TEAR study, [58][59][60] set in the Netherlands, evaluated two treatment options [ETN plus MTX and triple therapy (MTX + SSZ + HCQ)] and two timings regarding the initiation of therapy (immediately or step-up from MTX monotherapy if the DAS28-ESR was ≥ 3.2 at week 24). A total of 755 patients with early RA (symptom duration The TEAR study: results after 102 weeks (Moreland et al, 2010) This abstract by Moreland et al 59 provided preliminary data on radiographic scores by treatment type and by the timing of treatment initialisation; these data came from 297 participants.…”

Section: The Tear Studymentioning

confidence: 99%

See 4 more Smart Citations

The clinical effectiveness and cost-effectiveness of treat-to-target strategies in rheumatoid arthritis: a systematic review and cost-effectiveness analysis

Wailoo

Everson-Hock

Stevenson

et al. 2017

Health Technol Assess

View full text Add to dashboard Cite

Background Treat to target (TTT) is a broad concept for treating patients with rheumatoid arthritis (RA). It involves setting a treatment target, usually remission or low disease activity (LDA). This is often combined with frequent patient assessment and intensive and rapidly adjusted drug treatment, sometimes based on a formal protocol. Objective To investigate the clinical effectiveness and cost-effectiveness of TTT compared with routine care. Data sources Databases including EMBASE and MEDLINE were searched from 2008 to August 2016. Review methods A systematic review of clinical effectiveness was conducted. Studies were grouped according to comparisons made: (1) TTT compared with usual care, (2) different targets and (3) different treatment protocols. Trials were subgrouped by early or established disease populations. Study heterogeneity precluded meta-analyses. Narrative synthesis was undertaken for the first two comparisons, but was not feasible for the third. A systematic review of cost-effectiveness was also undertaken. No model was constructed as a result of the heterogeneity among studies identified in the clinical effectiveness review. Instead, conclusions were drawn on the cost-effectiveness of TTT from papers relating to these studies. Results Sixteen clinical effectiveness studies were included. They differed in terms of treatment target, treatment protocol (where one existed) and patient visit frequency. For several outcomes, mixed results or evidence of no difference between TTT and conventional care was found. In early disease, two studies found that TTT resulted in favourable remission rates, although the findings of one study were not statistically significant. In established disease, two studies showed that TTT may be beneficial in terms of LDA at 6 months, although, again, in one case the finding was not statistically significant. The TICORA (TIght COntrol for RA) trial found evidence of lower remission rates for TTT in a mixed population. Two studies reported cost-effectiveness: in one, TTT dominated usual care; in the other, step-up combination treatments were shown to be cost-effective. In 5 of the 16 studies included the clinical effectiveness review, no cost-effectiveness conclusion could be reached, and in one study no conclusion could be drawn in the case of patients denoted low risk. In the remaining 10 studies, and among patients denoted high risk in one study, cost-effectiveness was inferred. In most cases TTT is likely to be cost-effective, except where biological treatment in early disease is used initially. No conclusions could be drawn for established disease. Limitations TTT refers not to a single concept, but to a range of broad approaches. Evidence reflects this. Studies exhibit substantial heterogeneity, which hinders evidence synthesis. Many included studies are at risk of bias. Future work Future studies comparing TTT with usual care must link to existing evidence. A consistent definition of remission in studies is required. There may be value in studies to establish the importance of different elements of TTT (the setting of a target, the intensive use of drug treatments and protocols pertaining to those drugs and the frequent assessment of patients). Conclusion In early RA and studies of mixed early and established RA populations, evidence suggests that TTT improves remission rates. In established disease, TTT may lead to improved rates of LDA. It remains unclear which element(s) of TTT (the target, treatment protocols or increased frequency of patient visits) drive these outcomes. Future trials comparing TTT with usual care and/or different TTT targets should use outcomes comparable with existing literature. Remission, defined in a consistent manner, should be the target of choice of future studies. Study registration This study is registered as PROSPERO CRD42015017336. Funding The National Institute for Health Research Health Technology Assessment programme.

show abstract

Section: Assessment Of Cost-effectivenesssupporting

confidence: 59%

Section: Assessment Of Clinical Effectivenessmentioning

confidence: 99%

Section: Assessment Of Clinical Effectivenessmentioning

confidence: 99%

Section: Disease-modifying Antirheumatic Drug and Biologic Combinationsmentioning

confidence: 99%

Section: The Tear Studymentioning

confidence: 99%

See 3 more Smart Citations

The clinical effectiveness and cost-effectiveness of treat-to-target strategies in rheumatoid arthritis: a systematic review and cost-effectiveness analysis

Wailoo

Everson-Hock

Stevenson

et al. 2017

Health Technol Assess

View full text Add to dashboard Cite

show abstract

Impact of Biologic Agents With and Without Concomitant Methotrexate and at Reduced Doses in Older Rheumatoid Arthritis Patients

Zhang

Xie

Delzell

et al. 2015

Arthritis Care & Research

Self Cite

View full text Add to dashboard Cite

Background This study examines whether concomitant methotrexate (MTX) use is associated with better biologic persistence and whether self-administered anti-TNF therapies are used at reduced doses in real-world clinical care settings, not just clinical trials. Methods We conducted a retrospective cohort study among RA patients using Medicare claims data from 2006 to 2012. Subjects were new initiators of etanercept, infliximab, adalimumab, abatacept and tocilizumab with at least 12 months of continuous medical and pharmacy coverage after treatment initiation. We examined the association between concomitant MTX use and persistence on biologics using Cox proportional hazard regression adjusting for demographics and baseline co-morbidities. We further identified a subgroup of patients who initiated and were adherent on etanercept or adalimumab for at least 12 months and examined the proportion of patients who subsequently used these therapies at reduced doses continuously for an additional 12, 18, and 24 months. Results Of 26,510 eligible RA patients, 10,511 initiated biologic monotherapy. Overall, patients initiated biologic monotherapy were 1.4 (95% CI, 1.3–1.5) times more likely to discontinue at 1-year and 1.8 (95% CI, 1.7–2.0) times more likely if starting infliximab monotherapy. Approximately 10–20% of patients who initiated and adhered to etanercept and adalimumab for ≥ 12 months subsequently used reduced-dose therapy for an 12 additional months and beyond. Conclusion In real-world practice, concomitant MTX was associated with improved persistence on biologic therapy, especially for infliximab users; reduced-dose injectable anti-TNF therapy was used by a substantial proportion of RA patients.

show abstract

Comprehensive Appraisal of Magnetic Resonance Imaging Findings in Sustained Rheumatoid Arthritis Remission: A Substudy

Ranganath

Motamedi

Haavardsholm

et al. 2015

Arthritis Care & Research

Self Cite

View full text Add to dashboard Cite

Objective To evaluate the effect of sustained ACR/EULAR Boolean remission on residual joint inflammation assessed by magnetic resonance imaging (MRI) and to secondarily evaluate other clinical definitions of remission, within an early seropositive rheumatoid arthritis (RA) cohort. Methods A subcohort of 118 RA patients were enrolled from patients who completed the two-year double-blind randomized Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Patients received a single contrast enhanced 1.5 Tesla MRI of their most involved wrist. Two readers scored MRI for synovitis, osteitis, tenosynovitis, and erosions. Clinical assessments were performed every three months during the trial and at time of MRI. Results The subcohort was 92% seropositive with mean age 51 years, duration 4.1 months, and DAS28-ESR 5.8 at TEAR entry. Total MRI Inflammatory Scores (tenosynovitis+synovitis+osteitis) were lower among patients in clinical remission. Lower MRI scores were correlated with longer duration of CDAI remission (rho=0.22, p=0.03). At the time of MRI, 89 patients had no wrist pain/tenderness/swelling; however, all 118 patients had MRI evidence of residual joint inflammation after two years. No statistically significant differences in damage or MRI inflammatory scores were observed across treatment groups. Conclusion This is the first detailed appraisal describing the relationship between clinical remission cut-points and MRI inflammatory scores within a RA RCT. The most stringent remission criteria (2011 ACR/EULAR and CDAI) best differentiate the total MRI inflammatory scores. These results document that 2-years of triple therapy or TNF+methotrexate treatment in early RA does not eliminate MRI evidence of joint inflammation.

show abstract

Validation of the Methotrexate‐First Strategy in Patients With Early, Poor‐Prognosis Rheumatoid Arthritis: Results From a Two‐Year Randomized, Double‐Blind Trial

Cited by 75 publications

References 36 publications

The clinical effectiveness and cost-effectiveness of treat-to-target strategies in rheumatoid arthritis: a systematic review and cost-effectiveness analysis

The clinical effectiveness and cost-effectiveness of treat-to-target strategies in rheumatoid arthritis: a systematic review and cost-effectiveness analysis

Impact of Biologic Agents With and Without Concomitant Methotrexate and at Reduced Doses in Older Rheumatoid Arthritis Patients

Comprehensive Appraisal of Magnetic Resonance Imaging Findings in Sustained Rheumatoid Arthritis Remission: A Substudy

Contact Info

Product

Resources

About