Positioning biologics-A case-based discussion: Anti-tumor necrosis factor biological agents/biosimilars.

Abstract

The case presentations discussed in this session underscored the importance of developing treatment strategies that are both effective in maintaining disease control and that are tailored to individual patient needs. For each case, the role of anti-tumor necrosis factor (anti-TNF) treatments was advocated. In both cases, anti-TNF treatment was seen as the most appropriate option based on the patient's age, presentation and, in one case, desire for pregnancy. In both case presentations, treatment using an anti-TNF therapy was considered appropriate based on the evidence presented below. The role of biosimilars was discussed. The availability of biosimilars on the Pharmaceutical Benefits Scheme (PBS) immediately reduces the cost of the originator drug and allows for tendering for individual contracts on a state or hospital basis in an attempt to reduce pharmaceutical costs. Tumor necrosis factor has long been recognized as a pivotal inflammatory mediator in many chronic immune-mediated diseases. The development of monoclonal antibodies directed against TNF that induce and maintain remission have revolutionized targeted treatment for inflammatory bowel disease (IBD).1 These treatments commonly result in mucosal healing associated with improved clinical outcomes. Anti-TNF biological agents are the current mainstay biological treatments for Crohn's disease and ulcerative colitis in Australia.2 Even though this class of drug was first subsidized by the PBS in 2007, optimizing their use has only occurred in recent years. The benefit of thiopurine co-therapy is well-recognized for infliximab,3 and there is some evidence that thiopurine co-therapy may provide benefit when used with adalimumab.4 The therapeutic drug monitoring (TDM) revolution has provided clinicians with additional tools for this class of drug, and the recent Australian consensus statements on TDM in IBD5 illustrate the appropriate role of TDM in anti-TNF treatment optimization. Interventional strategies based on TDM-guidance include relevant, objective clinical outcomes that will further our knowledge on the optimal use of these drugs. The rapidity of action of anti-TNF agents make them ideal for hospitalized IBD patients, especially in the setting of acute severe ulcerative colitis where infliximab remains the only viable biological agent to date.6 All these advantages make anti-TNF a highly suitable biological agent treatment option in the setting of refractory IBD. Currently, in Australia, the persistence of anti-TNF therapies is low, with a median persistence of ~50% at 3 years.7 Persistence is significantly lower in elderly subjects, which might reflect the willingness for these subjects to undergo surgical resection or the concerns over systemic-immunosuppression leading to the development of opportunistic infections and skin or hematological malignancies. As such, anti-TNF biological agents are not uniformly embraced, and there is a need for alternative drugs with a lower potential for serious adverse effects. Alternative non-anti-TNF biological agents are now available and are more suitable in this subset of the IBD population. Primary non-response and secondary loss of response result in treatment failures and switch within- and out of class.5 The additional listing of golimumab, a subcutaneous anti-TNF agent for the treatment of ulcerative colitis, onto the PBS for reimbursement will further increase the access of anti-TNF agents for Australian IBD patients. The availability of biosimilars and incentives for their use will further modify the anti-TNF therapy treatment landscape. Anti-TNF therapies have by far the most patient years of usage, volume of publications, safety data, and experience in pregnancy of all biological therapies and are at present the most used class of biological agents in IBD. RL serves on advisory boards for Aspen, AbbVie, Celgene, Ferring, Hospira, Janssen-Cilag, MSD, Pfizer and Takeda. He has received educational grants from Shire, Janssen-Cilag and Takeda.