Biologics, Biosimilars Offer New Opportunities in Treatment of IBD
The wide range of biologics that have become available for IBD offer greater opportunities for successful treatment but also many challenges, according to a KEYNOTE presentation by Dr James Lindsay at the 2018 AIBD Meeting.
Ulcerative colitis (UC) and Crohn disease (CD) are progressive diseases, though symptoms occur in flares. As patients progress, their disease becomes more difficult to treat with standard salvage therapies, according to Lindsay, who is a consultant in gastroenterology at Barts Health NHS Trust and a member of the Governing Board of the European Crohn's and Colitis Organisation (ECCO). The introduction of biologics means providers now have potentially effective treatment options in these cases.
“This is an exciting time for our patients, as the proportion of drugs we have to use has increased,” Dr Lindsay said.
These include vedolizumab, ustekinumab, the Janus kinase (JAK) inhibitor therapy folgotinib, and the anti-tumor necrosis factor (TNF) therapies infliximab and adalimumab, as well as their biosimilars.
However, he cautioned, providers must use the right drugs in the right way. Because a first-line biologic has a greater chance of success than second-line, “we must make the most of our first-line choice,” he said.
Dr Lindsay discussed what he referred to as the “known knowns” of using biologics: all induce mucosal healing in some patients, and the rate observed in clinical trials mostly depends on population studied. He added that mucosal healing has become the new standard in outcome measures for IBD, as it is objective and has been associated with long-term clinical remission.
The degree of mucosal healing with biologics depends on current levels of drug exposure; in induction studies, higher trough levels of the drug are associated with multiple measures of mucosal healing. For this reason, he said, it is important to optimize drug exposure with therapeutic drug monitoring. He noted that disease burden, smoking, and obesity have all been reported as independent predictors of drug levels.
Another important consideration with the use of biologics is preventing the formation of antidrug antibodies. Concomitant immunomodulation is a good approach to reducing this risk, though the risk of serious infections does increase with combination therapy. Other risks to be mindful of include an increased risk of lymphoma with anti-TNF therapy, including with monotherapy. These factors should all be used to help position biologics within clinical practice, Dr Lindsay said.
Biologics are all effective but have subtle differences. Therefore, treatment decisions should be made on a patient-by-patient basis, Lindsay said.
In addition to the many biologics available for patients with IBD, the introduction of biosimilars has provided further choices for providers to make. Dr Lindsay shared his experience at Barts Health NHS Trust in shifting patients to biosimilars when available in order to reduce costs. He noted that biologic therapy is the biggest driver of cost for managing CD.
While the initial position of ECCO on biologics released in 2013 cautioned that clear evidence was needed before routinely switching patients from an original biologic to a biosimilar could be recommended, Dr Lindsay said he feels we now have that evidence. This includes data from the NOR-SWITCH study, in which patients doing well on Remicade (infliximab) were randomized to continue on the branded drug or switch to a biosimilar and had similar outcomes with either treatment. Another study of infliximab, in which patients were initially switched to a biosimilar and then were switched again 30 weeks later, also showed no significant differences between the groups at week 52 in terms of treatment response, disease remission, and quality of life outcomes.
On the basis of this data, Dr Lindsay’s practice decided to switch all of their patients from original biologics to biosimilars where available. He noted that they originally considered whether to switch only certain patients, but they concluded that all patients could be switched if the drugs are truly the same. Since biosimilars were implemented, Dr Lindsay reported that no patients have had any clinical problems since switching, and the practice has seen a 25-30% reduction in costs. They have used these profits to enhance their services to patients.
Furthermore, Dr Lindsay presented data showing that the overall proportion of patients who have received biologic treatment has increased since the implementation of biosimilars. This experience provides an important lesson to providers in how the use of biosimilars can improve patient access to appropriate therapies.
–Kara Rosania
Reference:
Lindsay J. KEYNOTE: Lessons from ECCO: A European perspective on positioning biologics and biosimilars. Presented at: Advances in Inflammatory Bowel Diseases; December 13-15, 2018; Orlando, FL. https://www.consultant360.com/meetings/aibd.