Long-Term Safety of ADA in RA: Vaccination Responses and Obstetric Outcomes

An analysis of the safety profile of adalimumab for moderately to severely active rheumatoid arthritis RA over 10 years confirmed the overall good, established safety profile.

Analysis of the long-term safety profile of adalimumab (ADA) identified no new safety risks related to laboratory abnormalities, hepatitis B reactivation, and pregnancy outcomes in patients with moderate to severe rheumatoid arthritis (RA), according to research published in the Annals of the Rheumatic Diseases.

Gerd R. Burmester, MD, Department of Rheumatology and Clinical Immunology, Charite-University Medicine in Berlin, and colleagues, conducted an analysis of 15 132 patients exposed to ADA through global clinical trials. The researchers noted any adverse events of interest, including overall infections, laboratory abnormalities, and any adverse events associated with the influenza vaccination. Pregnancy outcome data were collected from the Adalimumab Pregnancy Registry.

High Yield Data Summary

  • Influenza-related AEs occurred in 5% of vaccinated patients taking ADA compared with 14% of patients not vaccinated taking ADA
  • Relative risks of major birth defects and spontaneous abortions in women on ADA were similar to those not on ADA and healthy women

Serious infections and tuberculosis were found at a rate of 4.7 and 0.3 events per 100 patient-years, respectively; 2 patients experienced reactivation of hepatitis B.

No significant laboratory abnormalities were reported when ADA was co-administered with methotrexate, as compared to when placebo was administered with methotrexate.  

Influenza-related adverse events occurred in 5% of vaccinated patients compared with 14% of patients not vaccinated. Patients on ADA should thus be counseled regarding influenza vaccination.

Relative risks of major birth defects and spontaneous abortions in women taking ADA were similar to those women with RA not taking ADA and healthy women.

Summary and Clinical Applicability

“This analysis confirms and expands the known safety profile of ADA and reports no additional safety risk of laboratory abnormalities, hepatitis B reactivation and pregnancy outcomes, including spontaneous abortions and birth defections,” Dr Bermester concluded. “The benefits of influenza vaccination are reinforced.” 

Limitations and Disclosures

This study was limited by restricting data analysis to clinical trial experience, which may not fully reflect clinical practice due to selection bias of trial populations, survival of participants, and preexisting comorbidities.

“Comparisons with other treatments are limited due to the lack of a control group with any specific active treatment,” noted Dr Bermester.

AbbVie funded the study, contributed to the design, was involved with the collection, analysis, and interpretation of the data, and in the writing review and approval of the publication. Medical writing support was offered by AbbVie employees. Dr Bermester has received research grants, consulting fees, and speaker’s fees from AbbVie, BMS, Merck, Pfizer, Roche, and UCB.


Burmester GR, Landewé R, Genovese MC, et al. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2016  Published online ahead of print June 23, 2016.  doi: 10.1136/ammrheumdis-2016-209322