Objective To compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to ...methotrexate.Design Systematic review and Bayesian random effects network meta-analysis of trials assessing methotrexate used alone or in combination with other conventional synthetic DMARDs, biologic drugs, or tofacitinib in adult patients with rheumatoid arthritis.Data sources Trials were identified from Medline, Embase, and Central databases from inception to 19 January 2016; abstracts from two major rheumatology meetings from 2009 to 2015; two trial registers; and hand searches of Cochrane reviews.Study selection criteria Randomized or quasi-randomized trials that compared methotrexate with any other DMARD or combination of DMARDs and contributed to the network of evidence between the treatments of interest.Main outcomes American College of Rheumatology (ACR) 50 response (major clinical improvement), radiographic progression, and withdrawals due to adverse events. A comparison between two treatments was considered statistically significant if its credible interval excluded the null effect, indicating >97.5% probability that one treatment was superior.Results 158 trials were included, with between 10 and 53 trials available for each outcome. In methotrexate naive patients, several treatments were statistically superior to oral methotrexate for ACR50 response: sulfasalazine and hydroxychloroquine (“triple therapy”), several biologics (abatacept, adalimumab, etanercept, infliximab, rituximab, tocilizumab), and tofacitinib. The estimated probability of ACR50 response was similar between these treatments (range 56-67%), compared with 41% with methotrexate. Methotrexate combined with adalimumab, etanercept, certolizumab, or infliximab was statistically superior to oral methotrexate for inhibiting radiographic progression, but the estimated mean change over one year with all treatments was less than the minimal clinically important difference of 5 units on the Sharp-van der Heijde scale. Triple therapy had statistically fewer withdrawals due to adverse events than methotrexate plus infliximab. After an inadequate response to methotrexate, several treatments were statistically superior to oral methotrexate for ACR50 response: triple therapy, methotrexate plus hydroxychloroquine, methotrexate plus leflunomide, methotrexate plus intramuscular gold, methotrexate plus most biologics, and methotrexate plus tofacitinib. The probability of response was 61% with triple therapy and ranged widely (27-70%) with other treatments. No treatment was statistically superior to oral methotrexate for inhibiting radiographic progression. Methotrexate plus abatacept had a statistically lower rate of withdrawals due to adverse events than several treatments.Conclusions Triple therapy (methotrexate plus sulfasalazine plus hydroxychloroquine) and most regimens combining biologic DMARDs with methotrexate were effective in controlling disease activity, and all were generally well tolerated in both methotrexate naive and methotrexate exposed patients.
This article describes conceptual advances of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group guidance to evaluate the certainty of evidence (confidence ...in evidence, quality of evidence) from network meta-analysis (NMA). Application of the original GRADE guidance, published in 2014, in a number of NMAs has resulted in advances that strengthen its conceptual basis and make the process more efficient. This guidance will be useful for systematic review authors who aim to assess the certainty of all pairwise comparisons from an NMA and who are familiar with the basic concepts of NMA and the traditional GRADE approach for pairwise meta-analysis. Two principles of the original GRADE NMA guidance are that we need to rate the certainty of the evidence for each pairwise comparison within a network separately and that in doing so we need to consider both the direct and indirect evidence. We present, discuss, and illustrate four conceptual advances: (1) consideration of imprecision is not necessary when rating the direct and indirect estimates to inform the rating of NMA estimates, (2) there is no need to rate the indirect evidence when the certainty of the direct evidence is high and the contribution of the direct evidence to the network estimate is at least as great as that of the indirect evidence, (3) we should not trust a statistical test of global incoherence of the network to assess incoherence at the pairwise comparison level, and (4) in the presence of incoherence between direct and indirect evidence, the certainty of the evidence of each estimate can help decide which estimate to believe.
•The application of the Grading of Recommendations Assessments, Development, and Evaluation approach to a number of network meta-analyses in the 3 years since the original guidance publication has led to advances that have strengthened the conceptual basis.•We present, discuss, and illustrate four conceptual advances. These are based on two principles: we need to rate the certainty of the evidence of each pairwise comparison within a network separately and that we need to consider both the direct and indirect evidence contributing to each network estimate.•Although maximizing the efficiency of the process is desirable, as illustrated in the conceptual advances, use of these strategies requires careful judgment.
There is increasing recognition of the importance of patient preferences and methodologies to measure them. In this article, methods to quantify patient preferences are reviewed, with a focus on ...discrete choice experiments. In a discrete choice experiment, patients are asked to choose between 2 or more treatments. The results can be used to quantify the relative importance of treatment outcomes and/or other considerations relevant to medical decision making. Conducting and interpreting a discrete choice experiment requires multiple steps and an understanding of the potential biases that can arise, which we review in this article with examples in rheumatic diseases.
Objective
To summarize the relationship between obesity and remission in rheumatoid arthritis (RA); secondary objectives were to summarize other measures of treatment response and mortality in RA.
...Methods
Medline and Embase searches were performed in March 2016 using relevant MeSH and keyword terms for obesity and RA. Articles were selected if they reported estimates for achieving remission in obese subjects relative to other body mass index (BMI) categories, or changes in composite or individual disease activity measures or patient‐reported outcomes during therapy, or mortality rates, in relation to BMI category or on a continuous scale. Remission outcomes were conducive to meta‐analysis, and all other outcomes were summarized.
Results
A total of 3,368 records were screened; we included 8 reporting remission rates, 9 reporting disease activity measures or patient‐reported outcomes, and 3 examining mortality by obesity status or BMI. Obese patients attain remission less frequently than nonobese and/or normal‐weight patients. In adjusted models, obese patients demonstrated lower odds of achieving remission (pooled odds ratio OR 0.57 95% confidence interval (95% CI) 0.45, 0.72) and sustained remission (pooled OR 0.49 95% CI 0.32, 0.74) relative to nonobese subjects. Most studies found obese patients to have worse Disease Activity Scores or Disease Activity Scores in 28 joints, tender joint counts, inflammatory markers, patient global evaluation scores, pain scores, and physical function scores during followup, but not worse swollen joint counts. Obesity was not associated with increased mortality.
Conclusion
Obesity decreases the odds of achieving remission in RA and negatively impacts disease activity and patient‐reported outcomes during therapy. Interventions to reduce BMI should be investigated for their ability to improve disease outcomes.
Background & Aims There is controversy regarding the best treatment for patients with Crohn’s disease because of the lack of direct comparative trials. We compared therapies for induction and ...maintenance of remission in patients with Crohn’s disease, based on direct and indirect evidence. Methods We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central databases, through June 2014. We identified randomized controlled trials (N = 39) comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies with placebo or an active agent for induction and maintenance of remission in adult patients with Crohn’s disease. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% credible interval (CrI). Results Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pair-wise comparisons of anti–tumor necrosis factor agents, infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4–7.7) and adalimumab (OR, 2.1; 95% CrI, 1.0–4.6) were superior to certolizumab for induction of remission. All treatments were superior to placebo for maintaining remission, except for the combination of infliximab and methotrexate. Adalimumab, infliximab, and infliximab + azathioprine were superior to azathioprine/6-mercaptopurine: adalimumab (OR, 2.9; 95% CrI, 1.6–5.1), infliximab (OR, 1.6; 95% CrI, 1.0–2.5), infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7–5.5) for maintenance of remission. Adalimumab and infliximab + azathioprine were superior to certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4–4.6) and infliximab + azathioprine (OR, 2.6; 95% CrI, 1.3–6.0). Adalimumab was superior to vedolizumab (OR, 2.4; 95% CrI, 1.2–4.6). Conclusions Based on a network meta-analysis, adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of remission of Crohn’s disease.
To summarize patients' preferences for disease-modifying antirheumatic drug (DMARD) therapy in rheumatoid arthritis (RA).
We conducted a systematic review to identify English-language studies of ...adult patients with RA that measured patients' preferences for DMARD or health states and treatment outcomes relevant to DMARD decisions. Study quality was assessed using a published quality assessment tool. Data on the importance of treatment attributes and associations with patient characteristics were summarized across studies.
From 7951 abstracts, we included 36 studies from a variety of countries. Most studies were in patients with established RA and were rated as medium- (n = 19) or high-quality (n = 12). The methods to elicit preferences varied, with the most common being discrete choice experiment (DCE; n = 13). Despite the heterogeneity of attributes in DCE studies, treatment benefits (disease improvement) were usually more important than both non-serious (6 of 8 studies) and serious adverse events (5 of 8), and route of administration (7 of 9). Among the non-DCE studies, some found that patients placed high importance on treatment benefits, while others (in patients with established RA) found that patients were quite risk averse. Subcutaneous therapy was often but not always preferred over intravenous therapy. Patient preferences were variable and commonly associated with the sociodemographic characteristics.
Overall, the results showed that many patients place a high value on treatment benefits over other treatment attributes, including serious or minor side effects, cost, or route of administration. The variability in patient preferences highlights the need to individualize treatment choices in RA.
Health equity considerations have not been incorporated into prior Canadian Rheumatology Association guidelines. Our objective was to identify the challenges and possible solutions to mitigate ...threats to health equity in rheumatoid arthritis (RA) care in Canada.
A consultation process informed selection of priority populations, determined to be rural and remote, Indigenous, elderly with frailty, first-generation immigrant and refugee, low income and vulnerably housed, and diverse gender and sex populations. Semistructured interviews were completed with patients with lived experience, healthcare providers, and equity-oriented researchers. These interviews probed on population factors, initial and ongoing healthcare access issues, and therapeutic considerations influencing RA care. Known or proposed solutions to mitigate inequities during implementation of service models for the population group were requested. The research team used a phenomenological thematic analysis model and mapped the data into a logic model. Solutions applicable to several population groups were proposed.
Thirty-five interviews were completed to identify realities for each population in accessing RA care. Five themes emerged as primary solutions to population-based inequities, including actively improving the patient-practitioner relationship, increasing accessibility and coordination of care through alternative models of care, upholding autonomy in treatment selection while actively addressing logistical barriers and individualized therapy needs, collaborating with health supports valued by the patient, and being advocates for policy change and health system restructuring to ensure appropriate resource redistribution.
The challenges for populations facing inequities in rheumatology care and promising solutions should inform guideline development and implementation, policy change, and health system restructuring.
To quantify patient preferences for maintenance therapy of Crohn's disease and understand the impact on treatment selection.
We conducted a discrete-choice experiment in patients with Crohn's disease ...(n = 155) to measure the importance of attributes relevant to choosing between different medical therapies for maintenance of Crohn's disease. The attributes included efficacy and withdrawals due to adverse events, as well as dosing and other rare risks of treatment. From the discrete-choice experiment we estimated the part-worth (importance) of each attribute level, and explored preference heterogeneity through latent class analysis. We then used the part-worths to apply weights across each outcome from a prior network meta-analysis to estimate patients' preferred treatment in pairwise comparisons and for the overall group of treatments.
The discrete-choice experiment revealed that maintaining remission was the most important attribute. Patients would accept a rare risk of infection or cancer for a 14% absolute increased chance of remission. Latent class analysis demonstrated that 45% of the cohort was risk averse, either to adverse events or requiring a course of prednisone. When these preferences were used in modelling studies to compare pairs of treatments, there was a ≥ 78% probability that all biologic treatments were preferred to azathioprine and methotrexate, based on the balance of benefits and harms. When comparing all treatments, adalimumab was preferred by 53% of patients, who were motivated by efficacy, and vedolizumab was preferred by 30% who were driven by the preference to avoid risks. However, amongst biologic treatment options, there was considerable uncertainty regarding the preferred treatment at the individual patient level.
Patients with Crohn's disease from our population were, on average, focused on the benefits of treatment, supporting intensive treatment approaches aimed at maintaining remission. Important preference heterogeneity was identified, however, highlighting the importance of shared decision making when selecting treatments.
Objective
To conduct a systematic review on patient outcomes of virtual care compared to conventional care in rheumatoid arthritis (RA), including disease activity and patient experience.
Methods
A ...systematic search of Medline, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials was performed from database inception to March 19, 2020. Observational and randomized controlled trials (RCTs) describing the use of RA virtual care supplanting conventional visits and reporting on disease activity and/or patient experience were included. A narrative synthesis of results was conducted, as a meta‐analysis was not possible due to heterogeneity of study designs and outcome reporting.
Results
A total of 352 studies were identified, and 6 were selected for final inclusion: 3 RCTs and 3 observational studies. Disease activity and patient experience were comparable between virtual and conventional care models. In addition, 1 RCT found no difference in observed outcomes between virtual care delivered by a rheumatologist and by a rheumatology nurse. Virtual care was found to have additional benefits for improved treatment adherence, maintenance of functional status, and quality of life. The overall risk of bias was low in 2 of 3 RCTs, but high in the observational studies. Study quality was limited by incomplete data reporting, lack of sample size justification, and sufficient timeframe to assess objectives.
Conclusion
Limited evidence exists that virtual RA care is an acceptable alternative to conventional care, maintaining comparable patient outcomes and experience of care. Additional research into effective implementation strategies and long‐term health system and patient outcomes of virtual care are needed.
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