Forskning

Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis

Publikation: Forskning - peer reviewTidsskriftartikel

DOI

  • Simon Tarp
    Simon TarpMusculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Daniel Eric Furst
    Daniel Eric FurstMusculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Maarten Boers
    Maarten BoersMusculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • George Luta
  • Henning Bliddal
    Henning BliddalMusculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Ulrik Tarp
  • Karsten Heller Asmussen
    Karsten Heller AsmussenMusculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Birgitte Brock
  • Anna Dossing
    Anna DossingMusculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Tanja Schjødt Jørgensen
    Tanja Schjødt JørgensenMusculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Steffen Thirstrup
    Steffen ThirstrupMusculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • Robin Christensen
    Robin ChristensenMusculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark Robin.Christensen@regionh.dk.
OBJECTIVES:
To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.

METHODS:
Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).

RESULTS:
A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates.

CONCLUSION:
Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs.
OriginalsprogEngelsk
TidsskriftRheumatology
ISSN1462-0324
DOI
StatusUdgivet - 24 dec. 2016

    Emneord

  • Biological agents, Indirect comparison, Meta-analysis, Mortality, Network meta-analysis, Rheumatoid arthritis, Serious adverse events, Systematic review, Targeted synthetic disease-modifying antirheumatic drugs

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