Safety of synthetic and biological DMARDs: A systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis

Sofia Ramiro, Cécile Gaujoux-Viala, Jackie L. Nam, Josef S. Smolen, Maya Buch, Laure Gossec, Désirée Van Der Heijde, Kevin Winthrop, Robert Landewé

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Abstract

Objectives To update the evidence for the safety of synthetic disease-modifying antirheumatic drugs (sDMARDs), glucocorticoids (GC) and biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism (EULAR) recommendations for the management of RA. Methods Systematic literature review (SLR) of observational studies (including registries). Interventions were any bDMARD (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab or certolizumab pegol) or sDMARD (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, gold/auranofin, azathioprine, chlorambucil, chloroquine, cyclosporin, cyclophosphamide, mycophenolate, minocycline, penicillamine, tacrolimus or tofacitinib) and a comparator was required. Information on GCs was collected from the included studies. All safety outcomes were included. Results Forty-nine observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria. Substantial heterogeneity precluded meta-analysis of any of the outcomes. Patients on tumour necrosis factor inhibitors (TNFi) compared to patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1-1.8), a higher risk of tuberculosis, and an increased risk of infection by herpes zoster cannot be excluded. Patients on TNFi did not have an increased risk for malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5). From the studies identified on conventional sDMARDs, no new safety signals were found. Conclusions The findings from this SLR confirm the known safety pattern of sDMARDs and bDMARDs for the treatment of RA.

Original languageEnglish (US)
Pages (from-to)529-535
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume73
Issue number3
DOIs
StatePublished - Mar 1 2014

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Antirheumatic Agents
Rheumatic Diseases
Rheumatoid Arthritis
Safety
leflunomide
Observational Studies
Tumor Necrosis Factor-alpha
Auranofin
Interleukin 1 Receptor Antagonist Protein
Hydroxychloroquine
Chlorambucil
Sulfasalazine
Minocycline
Biological Therapy
Penicillamine
Azathioprine
Chloroquine
Herpes Zoster
Tacrolimus
Skin Neoplasms

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Safety of synthetic and biological DMARDs : A systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. / Ramiro, Sofia; Gaujoux-Viala, Cécile; Nam, Jackie L.; Smolen, Josef S.; Buch, Maya; Gossec, Laure; Van Der Heijde, Désirée; Winthrop, Kevin; Landewé, Robert.

In: Annals of the Rheumatic Diseases, Vol. 73, No. 3, 01.03.2014, p. 529-535.

Research output: Contribution to journalArticle

Ramiro, Sofia ; Gaujoux-Viala, Cécile ; Nam, Jackie L. ; Smolen, Josef S. ; Buch, Maya ; Gossec, Laure ; Van Der Heijde, Désirée ; Winthrop, Kevin ; Landewé, Robert. / Safety of synthetic and biological DMARDs : A systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. In: Annals of the Rheumatic Diseases. 2014 ; Vol. 73, No. 3. pp. 529-535.
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abstract = "Objectives To update the evidence for the safety of synthetic disease-modifying antirheumatic drugs (sDMARDs), glucocorticoids (GC) and biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism (EULAR) recommendations for the management of RA. Methods Systematic literature review (SLR) of observational studies (including registries). Interventions were any bDMARD (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab or certolizumab pegol) or sDMARD (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, gold/auranofin, azathioprine, chlorambucil, chloroquine, cyclosporin, cyclophosphamide, mycophenolate, minocycline, penicillamine, tacrolimus or tofacitinib) and a comparator was required. Information on GCs was collected from the included studies. All safety outcomes were included. Results Forty-nine observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria. Substantial heterogeneity precluded meta-analysis of any of the outcomes. Patients on tumour necrosis factor inhibitors (TNFi) compared to patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1-1.8), a higher risk of tuberculosis, and an increased risk of infection by herpes zoster cannot be excluded. Patients on TNFi did not have an increased risk for malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5). From the studies identified on conventional sDMARDs, no new safety signals were found. Conclusions The findings from this SLR confirm the known safety pattern of sDMARDs and bDMARDs for the treatment of RA.",
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AU - Ramiro, Sofia

AU - Gaujoux-Viala, Cécile

AU - Nam, Jackie L.

AU - Smolen, Josef S.

AU - Buch, Maya

AU - Gossec, Laure

AU - Van Der Heijde, Désirée

AU - Winthrop, Kevin

AU - Landewé, Robert

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