Radiographic progression can still occur in individual patients with low or moderate disease activity in the current treat-to-target paradigm: real-world data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry.
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ABSTRACT:
SUBMITTER: Ten Klooster PM
PROVIDER: S-EPMC6852758 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
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Radiographic progression can still occur in individual patients with low or moderate disease activity in the current treat-to-target paradigm: real-world data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry.
Ten Klooster Peter M PM Versteeg Letty G A LGA Oude Voshaar Martijn A H MAH de la Torre Inmaculada I De Leonardis Francesco F Fakhouri Walid W Zaremba-Pechmann Liliana L van de Laar Mart M
Arthritis research & therapy 20191112 1
<h4>Background</h4>The aim of this retrospective study was to examine the longitudinal association between disease activity and radiographic damage in a cohort of patients with early RA (symptom onset < 1 year) treated according to treat-to-target (T2T) therapy.<h4>Methods</h4>Baseline to 3-year follow-up data were used from patients included in the DREAM remission induction cohort. Patients received protocolized T2T treatment, aimed at 28-joint disease activity score-erythrocyte sedimentation r ...[more]
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Project description:BackgroundAdjusting medication of patients with rheumatoid arthritis (RA) until predefined disease activity targets are met, i.e. Treat-to-Target (T2T), is the currently recommended treatment approach. However, not much is known about long-term cost-effectiveness of different T2T strategies.We model the 5-year costs and effects of a step-up approach (MTX mono - > MTX + csDMARD combination - > Adalimumab - > second anti-TNF) and an initial combination therapy approach (MTX + csDMARD - > MTX + csDMARD higher dose - > anti-TNFs) from the healthcare and societal perspectives, by adapting a previously validated Markov model.MethodsWe constructed a Markov model in which 3-monthly transitions between DAS28-defined health states of remission (≤2.6), low (2.6 < DAS28 ≤ 3.2), moderate (3.2 < DAS28 ≤ 5.1), and high disease activity (DAS28 > 5.1) were simulated. Modelled patients proceeded to subsequent treatments in case of non-remission at each (3-month) cycle start. In case of remission for two consecutive cycles medication was tapered, until medication-free remission was achieved. Transition probabilities for individual treatment steps were estimated using data of Dutch Rheumatology Monitoring registry Remission Induction Cohort I (step-up) and II (initial combination). Expected costs, utility, and ICER after 5 years were compared between the two strategies. To account for parameter uncertainty, probabilistic sensitivity analysis was employed through Gamma, Normal, and Dirichlet distributions. All utilities, costs, and transition probabilities were replaced by fitted distributions.ResultsOver a 5-year timespan, initial combination therapy was less costly and more effective than step-up therapy. Initial combination therapy accrued €16,226.3 and 3.552 QALY vs €20,183.3 and 3.517 QALYs for step-up therapy. This resulted in a negative ICER, indicating that initial combination therapy was both less costly and more effective in terms of utility gained. This can be explained by higher (±5%) remission percentages in initial combination strategy at all time points. More patients in remission generates less healthcare and productivity loss costs and higher utility. Additionally, higher remission percentages caused less bDMARD use in the initial combination strategy, lowering overall costs.ConclusionInitial combination therapy was found favourable over step-up therapy in the treatment of Rheumatoid Arthritis, when considering cost-effectiveness. Initial combination therapy resulted in more utility at a lower cost over 5 years.
| S-EPMC6487515 | biostudies-literature
Project description:BackgroundThe detection of statistically significant reductions in radiographic progression during clinical studies in patients with rheumatoid arthritis (RA) has become increasingly difficult over the past decade due to early-escape study designs and declining rates of progression in control-group patients. We investigated the impact of extremes of radiographic data (outliers) and baseline prognostic factors on detection of treatment effects, to provide guidance on future analysis of joint structural data in RA clinical trials.MethodsData were from two, phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib in adult patients with moderate to severe RA: ORAL Scan (NCT00847613) and ORAL Start (NCT01039688). These studies detected significant reductions in radiographic progression with tofacitinib 10 mg twice daily (BID) plus background methotrexate (ORAL Scan), and with tofacitinib 5 or 10 mg BID as monotherapy (ORAL Start). We evaluated mean changes from baseline in van der Heijde modified total Sharp score (mTSS) at month 6 and month 12, using analysis of covariance (ANCOVA). A trimmed analysis was used to deal with extremes of data. The impact of baseline prognostic factors on radiographic progression was evaluated using ANCOVA to analyze the mean change from baseline in mTSS for each factor in turn.ResultsThe analysis included data from 720 patients from ORAL Scan and 880 patients from ORAL Start. Trimmed analyses were unbiased for the true mean estimate and enabled us to remove the effect of influential extreme observations in the data set. Almost all patients had at least one poor prognostic factor at baseline (e.g., high level of disease activity, or positive for rheumatoid factor). The strongest predictor of treatment effect was the severity of radiographic damage at baseline.ConclusionsA trimmed analysis can establish whether any significant inhibition of structural damage is being driven by extremes of data, and should be one of the sensitivity analyses of choice for structural data in RA clinical trials. Furthermore, analysis of radiographic data based on baseline prognostic factors may reveal increased treatment effects. Application of these methods to analysis of radiographic data from clinical trials in patients with RA, allows a more complete interpretation of data.Trial registrationClinicaltrials.gov NCT00847613 (registered 17 February 2009) and NCT01039688 (registered 23 December 2009).
| S-EPMC5034418 | biostudies-literature
Project description:BACKGROUND: Where health economic studies are frequently performed using modelling, with input from randomized controlled trials and best guesses, we used real-life data to analyse the cost-effectiveness and cost-utility of a treatment strategy aiming to the target of remission compared to usual care in early rheumatoid arthritis (RA). METHODS: We used real-life data from comparable cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA inception cohort (usual care, UC). Both cohorts were followed prospectively using the DREAM registry methodology. All patients fulfilled the American College of Rheumatology criteria for RA and were included in the cohort at the time of diagnosis. The T2T cohort was treated according to a protocolised strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores were estimated from the Health Assessment Questionnaire. A health care perspective was adopted and direct medical costs were collected. The incremental cost effectiveness ratio (ICER) per patient in remission and incremental cost utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated over two and three years of follow-up. RESULTS: Two year data were available for 261 T2T patients and 213 UC patients; an extended follow-up of three years was available for 127 and 180 patients, respectively. T2T produced higher remission percentages and a larger gain in QALYs than UC. The ICER was € 3,591 per patient in remission after two years and T2T was dominant after three years. The ICUR was € 19,410 per QALY after two years and T2T was dominant after three years. CONCLUSIONS: We can conclude that treating to the target of remission in early RA is cost-effective compared with UC. The data suggest that in the third year, T2T becomes cost-saving.
| S-EPMC3884120 | biostudies-other
Project description:Nightmares are defined as repeated occurrences of extremely dysphoric and well-remembered dreams that usually involve subjective threats to survival, security, or physical integrity. Generally, they occur during rapid eye movement sleep (REMS) and lead to awakenings with distress and insufficient overnight sleep. Nightmares may occur spontaneously (idiopathic) or as recurrent nightmares. Recurrent nightmares cause significant distress and impairment in occupational and social functioning, as have been commonly observed in post-traumatic stress disorder, depression and anxiety. By contrast, during lucid dreaming (LD), subjects get insight they are dreaming and may even control the content of their dreams. These features may open a way to help those who suffer from nightmare disorder through re-significations of the dream scene, i.e., knowing that they are dreaming and having control over their dream content. Thus, lucid dreamers might be able to render nightmares normal dreams, thereby assuring a restoring sleep. The aim of the present study is to review the existing literature of the use of LD as an auxiliary tool for treatment of nightmares. We conducted a careful literature search for eligible studies on the use of LD treatment for nightmares. We observed that whereas LD may be a feasible aid in the treatment of patients with nightmares through minimizing their frequency, intensity and psychological distress, the available literature is still scarce and does not provide consistent results. We conclude therefore that more research is clearly warranted for a better estimation of the effective conductance and therapeutic outcome of LD treatment in clinical practice.
| S-EPMC6902039 | biostudies-literature
Project description:ObjectivesTo determine the baseline factors predictive of significant radiographic progression (SRP) in patients with moderately active rheumatoid arthritis (RA) despite receiving methotrexate (MTX).MethodsPatients from the MTX arm of the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) trial with sustained moderate RA (defined as ≥3.2 mean disease activity score in 28 joints ≤5.1 during the last 6 months of the first year) were analysed for SRP (mTSS >3.0 overall) after 2 and 3 years. Baseline predictors for SRP were identified by univariate and multivariate analyses. All variables shown to be significantly associated with SRP were categorised based on clinically relevant cut-offs and tertiles and were included in a matrix risk model.Results228 patients were assigned MTX treatment, 210 patients were in the radiographic intention-to-treat population, and 96 of these had sustained moderate RA. SRP occurred in 25 (26%) and 33 (34%) patients after 2 and 3 years of MTX treatment, respectively. Univariate and multivariate analyses found that C reactive protein (CRP) and rheumatoid factor (RF) positivity at baseline were predictive of SRP after 2 and 3 years (p<0.05 for all). The matrix risk model showed that RF positivity and CRP levels >40 mg/L at baseline were significantly associated with SRP after 2 (p<0.05 for both; R(2)=0.24) and 3 years (p<0.05 for both; R(2)=0.22). The baseline erosion score was not found to be predictive of SRP.ConclusionsPatients with sustained moderate RA despite receiving MTX treatment are at risk of SRP, with both RF positivity and high CRP levels shown to be predictive of this.
| S-EPMC4613151 | biostudies-literature
Project description:BackgroundTo evaluate baseline hemoglobin (Hb) and radiographic progression over time in patients enrolled in the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registry.MethodsThe BRASS is a prospective observational registry of patients with rheumatoid arthritis. BRASS Hb data and total sharp score data were matched with the main BRASS patients. Hb at baseline was categorized per the World Health Organization guidelines. Mean Hb, mean total sharp score, and mean changes over time from baseline to month 120 were summarized (overall, by low/normal Hb, and by current medication at baseline). All analyses were descriptive.ResultsOut of the total (N = 1114) rheumatoid arthritis patients included in the analysis, patients with low Hb at baseline (n = 224 [20%]) had longer disease duration and higher disease activity and reported more pain compared with patients with normal Hb at baseline (n = 890 [80%]). Patients with low Hb at baseline continued to have lower Hb than patients with normal Hb throughout 10 years; although, on average, patients in the low Hb subgroup exhibited a steady increase in Hb levels. A larger increase in total sharp score over time was observed for patients with low Hb than for patients with normal Hb. No meaningful differences potentially attributable to medication at baseline were detected.ConclusionsPatients with low Hb levels at baseline tended to have increased radiographic progression as measured by total sharp score compared with patients with rheumatoid arthritis having normal Hb levels. Patients with low Hb experienced sustained improvements in Hb levels over time, regardless of the class of medication used.Trial registrationClinicalTrials.gov NCT01793103.
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Project description:Immunotherapy is increasingly used in the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) are safe and effective ways to elicit immunotherapeutic responses. In 2015, daratumumab has become the first mAb approved by the Food and Drug Administration for clinical use in MM and, in the last 5 years, a lot of clinical and preclinical research has been done to optimize the use of this drug class. Currently, mAbs have already become part of standard-of-care combinations for the treatment of relapsed/refractory MM and very soon they will also be used in the frontline setting. The success of simple mAbs ('naked mAbs') prompted the development of new types of molecules. Antibody-drug conjugates (ADCs) are tumor-targeting mAbs that release a cytotoxic payload into the tumor cells upon antigen binding in order to destroy them. Bispecific antibodies (BiAbs) are mAbs simultaneously targeting a tumor-associated antigen and an immune cell-associated antigen in order to redirect the immune cell cytotoxicity against the tumor cell. These different constructs produced solid preclinical data and promising clinical data in phase I/II trials. The aim of this review article is to summarize all the recent developments in the field, including data on naked mAbs, ADCs and BiAbs.
| S-EPMC7662679 | biostudies-literature
Project description:BackgroundTo compare a treat-to-target (T2T) approach and routine care (RC) in adults with active to severely active rheumatoid arthritis (RA) initiating subcutaneous abatacept.MethodsA 12-month cluster-randomized trial in active RA patients treated with abatacept was conducted. Physicians were randomized to RC or T2T with a primary endpoint of achieving sustained Clinical Disease Activity Index (CDAI) low disease activity (LDA) at two consecutive assessments approximately 3 months apart. Additional outcomes included Simple Disease Activity Index (SDAI), Disease Activity Score 28-CRP (DAS28-CRP), Routine Assessment of Patient Index Data 3 (RAPID3), and the Health Assessment Questionnaire-Disability Index (HAQ-DI). Time to achieve therapeutic endpoints was assessed with survival analysis.ResultsAmong the 284 enrolled patients, 130 were in the T2T group and 154 in RC. Primary endpoint was achieved by 36.9% and 40.3% of patients in T2T and RC groups, respectively. No significant between-group differences were observed in the odds of achieving secondary outcomes, except for a higher likelihood of CDAI LDA in the T2T group vs. RC (odds ratio [95% confidence interval]: 1.33 [1.03-1.71], p = 0.0263). Compared with RC, patients in the T2T group achieved SDAI remission significantly faster (Kaplan-Meier-estimated mean [standard error]: 14.0 [0.6] vs. 19.3 [0.8] months, p = 0.0428) with a trend toward faster achievement of CDAI LDA/remission, DAS28-CRP remission, and HAQ-DI minimum clinically important difference.ConclusionsPatients managed per T2T and those under RC experienced significant improvements in RA disease activity at 12 months of abatacept treatment. T2T was associated with higher odds of CDAI LDA and a shorter time to achieving therapeutic endpoints.Trial registrationName of the registry: ClinicalTrials.gov.Trial registrationsNCT03274141 . Date of registration: September 6, 2017.
| S-EPMC10537125 | biostudies-literature
Project description:BackgroundWhile the availability of biological or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) has improved outcomes for rheumatoid arthritis (RA) patients, there remains a subset of individuals who fail to achieve low disease activity or remission despite multiple cycles of b/tsDMARDs. This state is referred to as 'difficult-to-treat (D2T)' RA.MethodsData from the Korean College of Rheumatology Biologics registry were utilized to analyze patients with RA who were treated with b/tsDMARDs.ResultsAmong 2,321 RA patients with RA treated with b/tsDMARDs, 271 (11.7%) were diagnosed with D2T RA. Lower age (OR = 0.98, p < 0.001), longer disease duration (OR = 1.06, p < 0.001), lower patient global assessment (OR = 0.89, p = 0.045), higher SDAI (OR = 1.06, p = 0.014) and RAPID3 (OR = 1.06, p = 0.002), lower RF positivity (OR = 0.65, p = 0.04), and lower prior use of methotrexate (OR = 0.44, p = 0.008), sulfasalazine (OR = 0.59, p = 0.003), and leflunomide (OR = 0.67, p = 0.013) were associated with D2T RA. The drug survival rate of b/tsDMARDs did not differ between patients with D2T RA and non-D2T RA (p = 0.35). However, the drug survival of individual b/tsDMARD differed between patients with D2T RA and non-D2T RA after eight years. Patients with D2T RA withdrew from b/tsDMARDs due to inefficacy more frequently than those without D2T RA (p < 0.001).ConclusionsD2T RA patients experienced higher disease activity despite maintaining b/tsDMARD therapy. Withdrawal rates due to inefficacy were higher in D2T RA. Effective therapeutic strategies are needed to improve disease control and treatment outcomes in this unique patient population.
| S-EPMC10507947 | biostudies-literature
Project description:Demonstrating inhibition of the structural damage to joints as a statistically significant difference in radiographic progression as measured by the van der Heijde modified Total Sharp Score (mTSS) is a common objective in trials for rheumatoid arthritis treatments. The frequently used analysis of the covariance model with missing data imputed using linear extrapolation (analyses of covariance, ANCOVA+LE) may not be ideal for long-term extension studies or for paediatric studies. The random coefficient (RC) model may represent a better alternative.A two-arm (active treatment and placebo) setting with a week 44 study period was considered. RC model, ANCOVA+LE and ANCOVA with last observation carried forward imputation were compared under different scenarios in bias, root mean square error (RMSE), power and type I error rate.The RC model outperformed ANCOVA+LE in metrics measuring bias, RMSE, power and type I error rate under the evaluated scenarios. ANCOVA and RC provide similar performance when there are no missing data. With missing data, RC+observed (OBS) provides similar or better results than ANCOVA+LE in power and bias.Our simulations support that RC is both a more sensitive and a more precise alternative to the commonly used ANCOVA+LE as a primary method for analysing mTSS in long-term extension and paediatric studies with a higher likelihood of missing data. The RC model can provide a reference at time points with missing data by estimating a slope; mTSS change by one unit change in time. ANCOVA+LE is recommended as a sensitivity analysis.
| S-EPMC10083852 | biostudies-literature