scholarly journals FRI0125 INDIVIDUAL PATIENT DATA META-ANALYSIS OF THE EFFECTIVENESS OF TOCILIZUMAB ON INHIBITING RADIOGRAPHIC PROGRESSION IN RHEUMATOID ARTHRITIS

Author(s):  
Maxime Verhoeven ◽  
Janneke Tekstra ◽  
Johannes W. G. Jacobs ◽  
M Jacob ◽  
van Laar ◽  
...  
2020 ◽  
pp. annrheumdis-2020-217171 ◽  
Author(s):  
Ricardo J O Ferreira ◽  
Paco M J Welsing ◽  
Johannes W G Jacobs ◽  
Laure Gossec ◽  
Mwidimi Ndosi ◽  
...  

ObjectivesTo determine the impact of excluding patient global assessment (PGA) from the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission criteria, on prediction of radiographic and functional outcome of rheumatoid arthritis (RA).MethodsMeta-analyses using individual patient data from randomised controlled trials testing the efficacy of biological agents on radiographic and functional outcomes at ≥2 years. Remission states were defined by 4 variants of the ACR/EULAR Boolean definition: (i) tender and swollen 28-joint counts (TJC28/SJC28), C reactive protein (CRP, mg/dL) and PGA (0–10=worst) all ≤1 (4V-remission); (ii) the same, except PGA >1 (4V-near-remission); (iii) 3V-remission (i and ii combined; similar to 4V, but without PGA); (iv) non-remission (TJC28 >1 and/or SJC28 >1 and/or CRP >1). The most stringent class achieved at 6 or 12 months was considered. Good radiographic (GRO) and functional outcome (GFO) were defined as no worsening (ie, change in modified total Sharp score (ΔmTSS) ≤0.5 units and ≤0.0 Health Assessment Questionnaire–Disability Index points, respectively, during the second year). The pooled probabilities of GRO and GFO for the different definitions of remission were estimated and compared.ResultsIndividual patient data (n=5792) from 11 trials were analysed. 4V-remission was achieved by 23% of patients and 4V-near-remission by 19%. The probability of GRO in the 4V-near-remission group was numerically, but non-significantly, lower than that in the 4V-remission (78 vs 81%) and significantly higher than that for non-remission (72%; difference=6%, 95% CI 2% to 10%). Applying 3V-remission could have prevented therapy escalation in 19% of all participants, at the cost of an additional 6.1%, 4.0% and 0.7% of patients having ΔmTSS >0.0, >0.5 and >5 units over 2 years, respectively. The probability of GFO (assessed in 8 trials) in 4V-near-remission (67%, 95% CI 63% to 71%) was significantly lower than in 4V-remission (78%, 74% to 81%) and similar to non-remission (69%, 66% to 72%).Conclusion4V-near-remission and 3V-remission have similar validity as the original 4V-remission definition in predicting GRO, despite expected worse prediction of GFO, while potentially reducing the risk of overtreatment. This supports further exploration of 3V-remission as the target for immunosuppressive therapy complemented by patient-oriented targets.


BMJ ◽  
2020 ◽  
pp. m2288 ◽  
Author(s):  
Kirsten Janke ◽  
Katharina Biester ◽  
Dietmar Krause ◽  
Bernd Richter ◽  
Christoph Schürmann ◽  
...  

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.


2020 ◽  
Author(s):  
Gregory Bisson ◽  
Mayara Bastos ◽  
Jonathon R. Campbell ◽  
Didi Bang ◽  
James C. Brust ◽  
...  

2020 ◽  
Author(s):  
Marjolein Ankersmit ◽  
Martijn W. Heymans ◽  
Otto Hoekstra ◽  
Stijn L. Vlek ◽  
Linda J. Schoonmade ◽  
...  

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