Immunogenicity & Clinical Response

Some patients treated with TNFis may develop ADAbs, which may be associated with reduced clinical response^1-9,*^,†

From a meta-analysis of 68 studies (RA, SpA and IBD) which evaluated 14,651 patients, 8766 patients had RA.^1,‡

Percentage of ADAbs by Disease and Drug¹

Adapted from Thomas SS, et al. 2015.

Overall effect of ADAbs on TNFi response²

From a meta-analysis of 12 studies (RA, SpA, PsO and IBD) which evaluated 865 patients, 540 patients had RA.^2,§

Risk ratio=0.32 (95% CI, 0.22-0.48)

Adapted from Garcês S, et al. 2013.

*Many factors impact the efficacy and safety of biologics and how an individual patient responds to a biologic. The presence or absence of neutralising ADAbs is one of these factors but does not lead to any conclusions about the overall efficacy and safety of the drug. The occurrence of ADAbs is also influenced by several factors, including co-treatment with immunosuppressive drugs such as MTX. As immunogenicity analyses are product-specific, comparison of antibody production rates with those from other products is not appropriate. ADAbs can be neutralising or non-neutralising and both may impact the bioavailability and safety of the drug. Neutralising antibodies bind to the binding site of the therapeutic protein and neutralise it, whereas non-neutralising antibodies bind to the therapeutic protein but do not neutralise it.¹⁰

^†Antibodies to Enbrel^® have been detected in the sera of some subjects treated with it. These antibodies have all been non-neutralising and are generally transient. There appears to be no correlation between antibody development and clinical response or AEs.¹¹

^‡Study design: Thomas SS, et al. 2015.

The objective of this study was to examine the immunogenicity of TNFi (Enbrel^®, adalimumab, infliximab, golimumab and certolizumab) in RA, SpA and IBD and to examine the potential effect of ADAbs on the loss of clinical response through a systematic literature review and meta-analysis.¹

A comprehensive literature search was conducted using 3 databases (PubMed, Web of Science and the Cochrane Library) to identify studies examining the immunogenicity of TNFi in autoimmune diseases between 1966 and 31 December 2013. Inclusion criteria required that the studies be written in English, and also that they be RCTs, observational studies or case reports involving more than 5 patients, and that the patients be aged 18 years or older. Studies were excluded if they were strictly genetic with no clinical correlation, if the patients had concomitant cancer within 5 years of the study or if the patients had a renal disease requiring dialysis. Double extraction was followed by a third extraction if needed.¹ Random-effect models were generated for the meta-analysis of 68 studies (N=14,651) to estimate the OR of the ADAb effects on TNFi response. Regression analysis was used to compare among the drugs and diseases.¹

^§Study design: Garcês S, et al. 2015.

The objective of this systematic review and meta-analysis was to assess the effect of ADAbs on drug response to Enbrel^®, adalimumab and infliximab, and the effect of immunosuppression on ADAb detection in patients with RA, SpA, PsO and IBD. A literature search was conducted using 3 databases (PubMed, EMBASE and the Cochrane Library) through 19 August 2012. Out of 2082 studies, 17 were used in the analysis: 1 RCT and 16 observational studies.²
Risk ratios (with uncertainty expressed by 95% CI) were calculated and random-effect models were used to cluster the results.²

Disclaimer: The results on Etanercept are from indications of RA and SpA.

ADAb, anti-drug antibody; AE, adverse event; CI, confidence interval; IBD, inflammatory bowel disease; MTX, methotrexate; OR, odds ratio; PsO, psoriasis; RA, rheumatoid arthritis; RCT, randomised control trial; SpA, spondyloarthritis; TNFi, tumour necrosis factor inhibitor.

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