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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Remission in early rheumatoid arthritis

MH Ma, IC Scott, GH Kingsley, and DL Scott.

Review published: 2010.

Link to full article: [Journal publisher]

CRD summary

This review found that combination therapies that used disease-modifying antirheumatic drugs increased remissions and reduced radiological progression in patients with rheumatoid arthritis. Given the clinical heterogeneity in the included studies, the potential for bias in the review process and the unknown quality of some studies, the authors' conclusions should be treated with caution.

Authors' objectives

To identify the frequency of remission according to different criteria, assess the influence of different treatment strategies on remission, and assess the effects of remission on radiological outcomes in patients with rheumatoid arthritis.

Searching

PubMed and EMBASE were searched from 1996 to 2008 for relevant studies published in English; search terms were reported.

Study selection

Randomised controlled trials (RCTs) or observational studies of patients with rheumatoid arthritis (according to the American College of Rheumatology/ACR criteria) were eligible for inclusion in the review. Eligible studies had to include more than 40 patients and use ACR or Disease Activity Score (DAS) remission as an outcome measure. Eligible patients had to have disease duration of less than three years from diagnosis. Radiological outcomes of patients in remission were also included.

The mean age of patients ranged from 46 to 58 years in the included observational studies and 48 to 59 years in the included RCTs (where reported). The percentage of females ranged from 61 to 81% in the observational studies and 52 to 86% in the RCTs. Disease duration criteria ranged from up to three months to less than 24 months in the observational studies and from less than six months to less than 36 months in the RCTs. Observational studies assessed the effects of disease-modifying antirheumatic drug (DMARD) monotherapy or DMARD combination therapy on outcomes; RCTs assessed monotherapy versus placebo or nonsteroidal anti-inflammatory drugs, monotherapy versus monotherapy, monotherapy versus combination therapy, or combination therapy versus combination therapy. Prevalence of remission was mostly measured at the end of the studies.

Two reviewers independently selected studies for eligibility, with differences resolved by consensus.

Assessment of study quality

RCTs were assessed for quality using the 5-point Jadad scale. Composite scores were calculated.

The authors did not state how many reviewers assessed studies for quality.

Data extraction

Data were extracted on the prevalence of ACR or DAS remission; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Data were also extracted on radiological progression in participants with remission, according to how this was defined in the individual studies.

Two reviewers independently extracted data, with differences resolved by consensus.

Methods of synthesis

All studies were synthesized in narrative format and presented separately according to study design, either observational studies or RCTs. RCTs were also pooled in meta-analyses, with summary odds ratios and 95% confidence intervals calculated, using the DerSimonian Laird random-effects model to compare effects on remission rates of DMARD monotherapy versus DMARD combination therapy.

Heterogeneity was assessed using the χ2 and I2. The number needed to treat (NNT) with 95% confidence intervals for some outcomes was calculated. Where RCTs had more than one treatment or control arm, the arm with the best outcome was selected for the pooled analysis.

Subgroup analyses were performed to assess the effects of steroids, anti-tumour necrosis factor (TNF), different combination therapies and tight-control regimens.

Results of the review

Seventeen observational studies (n=4,762 patients) and 20 RCTs (n=4,290 patients) were included in the review. The mean Jadad score for the RCTs was 3.5 (range 1 to 5). Duration of follow-up was one to 10 years in the observational studies and one to three years in the RCTs.

Remission

For observational studies (17 studies), the mean remission rate with disease-modifying antirheumatic drug (DMARD) monotherapy or combination therapy was 17% (eight studies) using ACR (American College of Rheumatology) criteria and remission rate of 33% (nine studies) using DAS (Disease Activity Score) criteria.

For the four RCTs that compared DMARD monotherapy with placebo/other treatment/other DMARD monotherapies, the remission rate was 19% with DMARD monotherapy therapy (three RCTs) and 12% with placebo therapy (one RCT).

For the 13 RCTS that compared DMARD monotherapy with DMARD combination therapy, the mean remission rate with monotherapy was 16% and with combination therapy was 24% by ACR criteria (six RCTs). Combination therapy was associated with significantly higher ACR remission rates than monotherapy (OR 1.69, 95% CI 1.21 to 2.36; NNT 12, 95% CI 8 to 33; I2=0%; seven RCTs). Mean remission rate with monotherapy was 26% and with combination therapy was 42% by DAS criteria. Combination therapy was associated with significantly higher DAS remission rates than monotherapy (OR 2.01, 95% CI 1.46 to 2.78; NNT 6, 95% CI 5 to 8; I2=68.6%; seven RCTs).

For three RCTs that compared DMARD combination therapies, remission rates by any criteria were 43% of patients.

Radiological progression

For four observational studies, radiological progression ranged from 19 to 54% in patients with remission.

For two RCTs, less radiological progression was found with DMARD combination therapy when compared with DMARD monotherapy in patients with remission.

Authors' conclusions

Combination therapies using DMARD increased remissions and reduced radiological progression, but standardisation of remission criteria was needed.

CRD commentary

The review addressed three clear research questions. Inclusion criteria appeared appropriate. A range of relevant sources were used to identify studies, but restrictions to journal publication and English language meant that publication and language bias could not be ruled out. Appropriate methods were used to select studies and extract data.

Observational studies were not appraised for quality, so it is difficult to assess the reliability of results based on these studies. RCTs were appraised for quality using an appropriate tool and composite scores were calculated, but the authors did not state how many reviewers performed the assessment. RCTs ranged from poor to good, but quality was not used to assess the reliability of the findings.

There was wide variation in study design (observational studies and RCTs), duration of follow-up (12 to 120 months), interventions (DMARD monotherapy and intensive combination regimens) and classification of remission (ACR and DAS criteria). There was a discrepancy between text and tables in the reporting of the lower limit of follow-up in observational studies. Given the clinical heterogeneity between the studies, the decision to synthesize the studies in narrative format, in separate groups according to study design, was appropriate. Where possible, when direct comparisons were made between therapies, studies were appropriately pooled in meta-analyses and conclusions on the optimum treatment type to enhance remission rates were based on these comparisons.

Given the clinical heterogeneity in the included studies, the potential for bias in the review process and the unknown quality of some studies, the authors' conclusions should be treated with caution.

Implications of the review for practice and research

Practice: The authors stated that remission was a realistic treatment goal in early rheumatoid arthritis. Available remission criteria were not directly comparable and standardisation was needed through international consensus.

Research: The authors stated that radiological remission should be considered routinely in clinical trials.

Funding

American College of Rheumatology; National Institute for Health Research, UK.

Bibliographic details

Ma MH, Scott IC, Kingsley GH, Scott DL. Remission in early rheumatoid arthritis. Journal of Rheumatology 2010; 37(7): 1444-1453. [PubMed: 20516031]

Indexing Status

Subject indexing assigned by NLM

MeSH

Antibodies, Monoclonal /therapeutic use; Antirheumatic Agents /therapeutic use; Arthritis, Rheumatoid /drug therapy /pathology /physiopathology; Databases, Factual; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; Tumor Necrosis Factor-alpha /antagonists & inhibitors

AccessionNumber

12011000226

Database entry date

23/01/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 20516031