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.

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.