Comparative effectiveness of biological medicines in rheumatoid arthritis: systematic review and network meta-analysis including aggregate results from reanalysed individual patient data
BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2288 (Published 07 July 2020) Cite this as: BMJ 2020;370:m2288Linked Opinion
Lessons from a network meta-analysis of biologics in rheumatoid arthritis
- Kirsten Janke, researcher1,
- Katharina Biester, senior researcher1,
- Dietmar Krause, rheumatologist3,
- Bernd Richter, coordinating editor4,
- Christoph Schürmann, statistician2,
- Katharina Hirsch, statistician2,
- Helmut Hörn, researcher1,
- Michaela Florina Kerekes, data manager1,
- Petra Kohlepp, data manager1,
- Beate Wieseler, head of department1
- 1Drug Assessment Department, Institute for Quality and Efficiency in Health Care, Im Mediapark 8, Cologne 50670, Germany
- 2Medical Biometry Department, Institute for Quality and Efficiency in Health Care, Cologne, Germany
- 3Rheumatology Practice Gladbeck, Gladbeck, Germany
- 4Cochrane Metabolic and Endocrine Disorders Group, Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Correspondence to: B Wieseler beate.wieseler{at}iqwig.de
- Accepted 30 April 2020
Abstract
Objective To assess the comparative effectiveness of biological medicines in rheumatoid arthritis in sufficiently similar patient populations, based on the current definitions of key outcomes.
Design Systematic review and network meta-analysis including aggregate results from reanalysed individual patient data.
Data sources Clinical study reports and aggregate results from reanalyses of individual patient data on key outcomes for rheumatoid arthritis provided by study sponsors for studies conducted up to 2017, and several databases and registries from inception up to February 2017.
Eligibility criteria for selecting studies Randomised controlled trials investigating patient relevant outcomes in adults with rheumatoid arthritis treated with biological medicines in combination with methotrexate after methotrexate failure for at least 24 weeks.
Results 45 eligible trials were identified. Combining data from clinical study reports and aggregate results from reanalyses of individual patient data allowed extensive analyses yielding sufficiently similar populations and homogeneous study results for network meta-analyses, including up to 35 studies on eight biological medicines combined with methotrexate. These analyses showed few statistically significant differences between the combination treatments. For example, anakinra showed less benefit than almost all the other seven biological medicines regarding clinical remission or low disease activity (clinical disease activity index ≤2.8 or ≤10, respectively) and certolizumab pegol showed more harm than the other seven biological medicines regarding serious adverse events or infections. Some outcomes had very wide 95% confidence intervals, potentially implying unidentified differences between the eight biological medicines, but wide 95% confidence intervals were less prominent for low disease activity, serious adverse events, and infections. Owing to a lack of head-to-head trials, results were mainly based on indirect comparisons with a limited number of studies, and recently approved Janus kinase inhibitors could not be included.
Conclusions For patients with rheumatoid arthritis after methotrexate failure, only minor differences in benefits and harms were seen between biological medicines in combination with methotrexate. However, the analysis was hampered by a lack of long term direct comparisons. The substantial information gain achieved by the reanalysis of individual patient data calls for the routine availability of individual patient data.
Footnotes
Contributors: BW, KB, KJ, CS, DK, and BR conceived and designed the study. KJ, KB, CS, KH, DK, BR, and BW analysed and interpreted the data. KJ, KB, BW, and CS drafted the first version of the manuscript. KJ, KB, and HH screened studies for inclusion and KJ, HH, PK, and MFK extracted data. CS and KH checked data extraction and performed statistical analyses. All authors approved the final draft of the manuscript. BW is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding: This work was supported by the Institute for Quality and Efficiency in Health Care. No external financial support was received. Eight of the 10 authors are IQWiG employees and (as the remaining two authors) were involved in the study design and in the collection, analysis, and interpretation of data as well as in the writing of the report and the decision to submit the article for publication.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the Institute for Quality and Efficiency in Health Care for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: Additional data are available in the full (German language) report on the IQWiG website.13
The manuscript’s guarantor (BW) affirms that the manuscript is an honest, accurate, and transparent account of the review being reported; that no important aspects have been omitted; and that any discrepancies from the original protocol have been explained.
Dissemination to participants and related patient and public communities: The results of our study have been made available to the patient representatives who are part of the decision making body for which the original health technology assessment report was prepared and to patients and the public by publication of the health technology assessment report on IQWiG’s website. An easily understandable summary will be made available to patients and the public on IQWiG’s patient information website (English version: https://www.informedhealth.org/).
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