OPEN IN READ APP
JOURNAL ARTICLE
REVIEW

Immunogenicity of monoclonal antibodies against tumor necrosis factor used in chronic immune-mediated Inflammatory conditions: systematic review and meta-analysis

Jose Ramon Maneiro, Eva Salgado, Juan Jesus Gomez-Reino
JAMA Internal Medicine 2013 August 12, 173 (15): 1416-28
23797343

IMPORTANCE: Knowledge of the immunogenicity of biologic agents may be helpful for the development of strategies for treatment of chronic immune-mediated inflammatory diseases.

OBJECTIVE: To summarize the influence of antibodies against biologic agents (AABs [seropositivity]) on efficacy and safety in immune-mediated inflammatory diseases. DATA SOURCES MEDLINE, EMBASE, Cochrane Library, and the Web of Knowledge were searched for articles published in English, Spanish, French, Italian, or Portuguese between 2000 and March 2012. The search strategy focused on synonyms of diseases, immunogenicity, and biologic agents. Abstracts from 2001 to 2011 of the European League Against Rheumatism and American College of Rheumatology congresses were also included.

STUDY SELECTION: The selection criteria were (1) observational or interventional studies in rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, spondyloarthritis, and psoriasis; (2) studies including patients who received biologic agents; and (3) studies collecting data on AABs.

DATA EXTRACTION AND SYNTHESIS: Data collected included publication details, study design, characteristics of patients and treatments, presence of antibodies, and definition of response.

MAIN OUTCOMES AND MEASURES: The primary end point was the association of AABs with response to treatment. Secondary end points were the association of AABs with safety, the association of AABs with concentration of the drug, and the influence of use of concomitant immunosuppressive therapy in the formation of AABs.

RESULTS: The search captured 10 728 articles and abstracts. By hand and reverse search, 31 articles were additionally included. After evaluation of the full reports, 60 references were selected. They included 59 studies of anti-tumor necrosis factor monoclonal antibodies: 1 with etanercept, 2 with rituximab, and 2 with abatacept. In rheumatoid arthritis but not in inflammatory bowel disease or spondyloarthritis, seropositive patients presented worse clinical response at 6 months or less (odds ratio [OR], 0.03; 95% CI, 0.01-0.21), and at 6 months or more (0.03; 0.00-0.30) by meta-analysis. In rheumatoid arthritis, discontinuation of the biologic agent for all reasons was more common in seropositive patients (OR, 3.53; 95% CI, 1.60-7.82). In all conditions, seropositive patients had a higher risk of hypersensitivity reactions (OR, 3.97; 95% CI, 2.36-6.67). Overall, concomitant treatment with disease-modifying antirheumatic drugs, including azathioprine, decreased the risk of seropositivity (OR, 0.32; 95% CI, 0.25-0.42).

CONCLUSIONS AND RELEVANCE: Presence of antibodies against anti-tumor necrosis factor monoclonal antibodies confers a risk of discontinuation of treatment in rheumatoid arthritis and a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases. The combined use of anti-tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks. Information on other biologic agents is fragmentary.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
23797343
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"