Anti-TNF levels and anti-drug antibodies, immunosuppressants and clinical outcomes in inflammatory bowel disease

Abstract

The anti-tumor necrosis factor-α (TNF) antibodies have revolutionized the management of ulcerative colitis and Crohn’s disease. The development of assays to allow for the measurements of serum drug levels and anti-drug antibodies have provided a more objective means of therapeutic decision making, particularly among patients losing response to treatment. Additionally, more evidence is emerging that indicates the relationship between drug levels and response to therapy including clinical response, mucosal healing and sustained remission. The use of combination therapies of the anti-TNF agents and the thiopurine immunosuppressants may also decrease immunogenicity to the anti-TNF agents and potentiate response to therapy. With more evidence emerging evidence of the importance of therapeutic drug levels and anti-drug antibodies, clinicians may be able to better optimize the current arsenal of inflammatory bowel disease therapeutics to achieve greater rates of durable remission and improved quality of life.

Keywords:

• anti-drug antibodies
• anti-tumor necrosis factor agents
• Crohn’s disease
• immunogenicity
• immunosuppressants
• therapeutic drug levels
• ulcerative colitis

Financial & competing interests disclosures

A Kornbluth has acted as consultant, advisory board, received research support and/or speaker's bureau from Janssen, Abbvie, Prometheus, Takeda / Millennium, Pfizer, Bristol-Myers Squibb, Salix Pharmaceuticals and Warner-Chilcott. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• A sizeable percentage of initially anti-TNF responsive IBD patients lose response to these therapies over time typically due to sub-therapeutic drug levels, development of anti-drug antibodies, or the emergence of alternative pathways that lead to persistent inflammation.

• Clinical factors such as disease activity, hypoalbuminemia, elevated inflammatory markers and body mass impact may impact the pharmacokinetics of the anti-TNF agents and, subsequently, drug clearance and efficacy.

• The presence of anti-drug antibodies is predictive of loss of response or nonresponse to anti-TNF therapy.

• The clinical availability of assays to check anti-TNF levels and anti-drug antibodies may assist with therapeutic decision making among patients whom have lost response to their initial anti-TNF agent.

• A test-based strategy for therapeutic monitoring of anti-TNF treated IBD patients may be a cost-effective tool to aid in the decision between dose escalation versus medication substitution.

• The addition of a thiopurine to anti-TNF therapy increases drug levels and decreases immunogenicity, however, the optimal duration of combination therapy factoring infection and other adverse event risk remains to be determined.