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Cochrane Database of Systematic Reviews

Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis

Overview of attention for article published in Cochrane database of systematic reviews, May 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (78th percentile)
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Citations

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404 Mendeley
Title
Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis
Published in
Cochrane database of systematic reviews, May 2017
DOI 10.1002/14651858.cd012657
Pubmed ID
Authors

Jasvinder A Singh, Alomgir Hossain, Amy S Mudano, Elizabeth Tanjong Ghogomu, Maria E Suarez-Almazor, Rachelle Buchbinder, Lara J Maxwell, Peter Tugwell, George A Wells

Abstract

Biologic disease-modifying anti-rheumatic drugs (biologics) are highly effective in treating rheumatoid arthritis (RA), however there are few head-to-head biologic comparison studies. We performed a systematic review, a standard meta-analysis and a network meta-analysis (NMA) to update the 2009 Cochrane Overview. This review is focused on the adults with RA who are naive to methotrexate (MTX) that is, receiving their first disease-modifying agent. To compare the benefits and harms of biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib versus comparator (methotrexate (MTX)/other DMARDs) in people with RA who are naive to methotrexate. In June 2015 we searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE and Embase; and trials registers. We used standard Cochrane methods. We calculated odds ratios (OR) and mean differences (MD) along with 95% confidence intervals (CI) for traditional meta-analyses and 95% credible intervals (CrI) using a Bayesian mixed treatment comparisons approach for network meta-analysis (NMA). We converted OR to risk ratios (RR) for ease of interpretation. We also present results in absolute measures as risk difference (RD) and number needed to treat for an additional beneficial or harmful outcome (NNTB/H). Nineteen RCTs with 6485 participants met inclusion criteria (including five studies from the original 2009 review), and data were available for four TNF biologics (adalimumab (six studies; 1851 participants), etanercept (three studies; 678 participants), golimumab (one study; 637 participants) and infliximab (seven studies; 1363 participants)) and two non-TNF biologics (abatacept (one study; 509 participants) and rituximab (one study; 748 participants)).Less than 50% of the studies were judged to be at low risk of bias for allocation sequence generation, allocation concealment and blinding, 21% were at low risk for selective reporting, 53% had low risk of bias for attrition and 89% had low risk of bias for major baseline imbalance. Three trials used biologic monotherapy, that is, without MTX. There were no trials with placebo-only comparators and no trials of tofacitinib. Trial duration ranged from 6 to 24 months. Half of the trials contained participants with early RA (less than two years' duration) and the other half included participants with established RA (2 to 10 years). Biologic + MTX versus active comparator (MTX (17 trials (6344 participants)/MTX + methylprednisolone 2 trials (141 participants))In traditional meta-analyses, there was moderate-quality evidence downgraded for inconsistency that biologics with MTX were associated with statistically significant and clinically meaningful benefit versus comparator as demonstrated by ACR50 (American College of Rheumatology scale) and RA remission rates. For ACR50, biologics with MTX showed a risk ratio (RR) of 1.40 (95% CI 1.30 to 1.49), absolute difference of 16% (95% CI 13% to 20%) and NNTB = 7 (95% CI 6 to 8). For RA remission rates, biologics with MTX showed a RR of 1.62 (95% CI 1.33 to 1.98), absolute difference of 15% (95% CI 11% to 19%) and NNTB = 5 (95% CI 6 to 7). Biologics with MTX were also associated with a statistically significant, but not clinically meaningful, benefit in physical function (moderate-quality evidence downgraded for inconsistency), with an improvement of HAQ scores of -0.10 (95% CI -0.16 to -0.04 on a 0 to 3 scale), absolute difference -3.3% (95% CI -5.3% to -1.3%) and NNTB = 4 (95% CI 2 to 15).We did not observe evidence of differences between biologics with MTX compared to MTX for radiographic progression (low-quality evidence, downgraded for imprecision and inconsistency) or serious adverse events (moderate-quality evidence, downgraded for imprecision). Based on low-quality evidence, results were inconclusive for withdrawals due to adverse events (RR of 1.32, but 95% confidence interval included possibility of important harm, 0.89 to 1.97). Results for cancer were also inconclusive (Peto OR 0.71, 95% CI 0.38 to 1.33) and downgraded to low-quality evidence for serious imprecision. Biologic without MTX versus active comparator (MTX 3 trials (866 participants)There was no evidence of statistically significant or clinically important differences for ACR50, HAQ, remission, (moderate-quality evidence for these benefits, downgraded for imprecision), withdrawals due to adverse events,and serious adverse events (low-quality evidence for these harms, downgraded for serious imprecision). All studies were for TNF biologic monotherapy and none for non-TNF biologic monotherapy. Radiographic progression was not measured. In MTX-naive RA participants, there was moderate-quality evidence that, compared with MTX alone, biologics with MTX was associated with absolute and relative clinically meaningful benefits in three of the efficacy outcomes (ACR50, HAQ scores, and RA remission rates). A benefit regarding less radiographic progression with biologics with MTX was not evident (low-quality evidence). We found moderate- to low-quality evidence that biologic therapy with MTX was not associated with any higher risk of serious adverse events compared with MTX, but results were inconclusive for withdrawals due to adverse events and cancer to 24 months.TNF biologic monotherapy did not differ statistically significantly or clinically meaningfully from MTX for any of the outcomes (moderate-quality evidence), and no data were available for non-TNF biologic monotherapy.We conclude that biologic with MTX use in MTX-naive populations is beneficial and that there is little/inconclusive evidence of harms. More data are needed for tofacitinib, radiographic progression and harms in this patient population to fully assess comparative efficacy and safety.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 404 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 404 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 56 14%
Student > Master 55 14%
Researcher 52 13%
Student > Ph. D. Student 38 9%
Other 32 8%
Other 85 21%
Unknown 86 21%
Readers by discipline Count As %
Medicine and Dentistry 170 42%
Nursing and Health Professions 42 10%
Pharmacology, Toxicology and Pharmaceutical Science 16 4%
Computer Science 11 3%
Biochemistry, Genetics and Molecular Biology 10 2%
Other 53 13%
Unknown 102 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 December 2020.
All research outputs
#2,750,594
of 17,364,317 outputs
Outputs from Cochrane database of systematic reviews
#5,376
of 11,660 outputs
Outputs of similar age
#57,509
of 273,231 outputs
Outputs of similar age from Cochrane database of systematic reviews
#145
of 251 outputs
Altmetric has tracked 17,364,317 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,660 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 25.0. This one has gotten more attention than average, scoring higher than 53% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 273,231 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 78% of its contemporaries.
We're also able to compare this research output to 251 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.