Since 1997 when biologic therapies were first used as an inflammatory bowel disease (IBD) treatment, there has been a steep learning curve in how they can be used optimally to treat IBD. Researchers have found that, with biologic treatments, long-term IBD remission depends on several factors, including patient selection, the drug maintenance schedule, and the use of concurrent therapies.
Types of Biologic Treatments
Biologic treatments refer to monoclonal antibodies that are mainly used to treat chronic inflammatory conditions. For IBD, this includes anti-tumor necrosis factor (TNF) therapies as well as drugs that target integrins and interleukin.
List of Biologic Treatments
- Infliximab (Remicade®)
- Adalimumab (Humira®)
- Certolizumab (Cimzia®)
- Golimumab (Simponi®)
- Natalizumab (Tysabri®)
- Vedolizumab (Entyvio®)
- Ustekinumab (Stelara®)
Optimizing Biologic Therapy
When biologic anti-TNF agents were introduced in the U.S. and Europe in the late 1990s, initial studies provided evidence that biologics could induce long-term remission, reduce hospitalizations, and even prevent the need for surgical procedures.
However, follow-up studies have observed a large number of patients who initially obtain remission through biologics but have a reduced response to the drugs over time.
Of course, a large number of patients respond well to biologics and maintain remission over the long term without the need for adjustments or intervention. Others are not so lucky, and they continue to experience IBD symptoms despite the biologic therapy. A review published in Gastroenterology Report pointed to a study in which only 40% of patients were in still in remission a year after induction. Similarly, they found that, in clinical practice, less than 50% patients who originally responded to biologic medications were in remission at the one-year mark.
Why do some patients retain remission while others do not?
In recent years, researchers and physicians have asked this question and worked to develop strategies improve retention rates in biologic treatments. They found that these factors that weigh into retention:
- Whether or not the patient was prescribed the most appropriate treatment in the first place
- Using the correct dose for inducing remission
- Using the optimal dose for retaining remission
- Using combination therapy with an immunosuppressant
The importance of biologic maintenance schedules
The dose and the treatment schedule have an impact on retention rates. In fact, researchers believe that the right dosing strategy can help patients prevent the development of anti-drug antibodies, or ADAs—a response in some patients that renders the drug less effective.
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Many studies have linked low serum drug levels to increased development of anti-drug antibodies and loss of response to biologics. The majority of these studies were conducted on infliximab (Remicade) and showed that episodic use leads to increased ADAs and lower remission rates, while patients that followed a scheduled infliximab maintenance plan had fewer hospitalizations and higher response rates.
Based on these findings, it appears that it’s important for patients to maintain consistent drug serum levels to avoid undesirable responses.
Using therapeutic drug monitoring, healthcare professionals continue to refine the optimal biologic dosing strategy for each biologic drug. In an ideal world, each patient would undergo therapeutic drug monitoring to measure their individual response to the drug and adjust their dose accordingly. This is one reason why clinical trials can be beneficial. Especially in cases where new administrations or dosing strategies are being explored, patients benefit from the more in-depth monitoring and additional insight this provides.
Biologic maintenance schedules
Examples of the optimal maintenance schedules for several common biologic treatments are below:
Adalimumab Dosing Schedule
Induction dosing: 160 mg at week 0 and 80 mg at week 2.
Maintenance: 40 mg every other week. With adalimumab, the benefits might not be fully realized until 3 or 4 months into the ‘maintenance’ dosing phase. For this reason, physicians usually wait to escalate or adjust the maintenance dose until week 12.
Certolizumab Dosing Schedule
Induction dosing: 400 mg at weeks 0, 2, and 4
Maintenance: 400 mg every 4 weeks
Natalizumab Dosing Schedule
Induction dosing: 300 mg IV at weeks 0, 4, and 8
Maintenance: 300 mg IV every 4 weeks
Infliximab Dosing Schedule
Induction dosing: 5 mg/kg intravenously, given at weeks 0, 2, and 6
Maintenance: 5 mg/kg every 8 weeks
Combination therapy and IBD remission
In addition to following an optimal maintenance schedule, some studies show that patients can achieve longer-term remission with a biologic treatment when they supplement the biologic treatment with an immunosuppressant.
If you experience IBD symptoms even after achieving remission with a biologic therapy, talk to your GI about the possibility of combination therapy with an immunosuppressant.
Alan C. Moss. (2015). Optimizing the use of biological therapy in patients with inflammatory bowel disease. Gastroenterology Report, 3,(1); 63–68. Retrieved from https://doi.org/10.1093/gastro/gou087
Panaccione, R., & Ghosh, S. (2010). Optimal use of biologics in the management of Crohn’s disease. Therapeutic Advances in Gastroenterology, 3(3), 179–189. http://doi.org/10.1177/1756283X09357579