One of the complications of treatment with biologic medications is the formation of anti-drug antibodies. These antibodies can affect how well the drug works to treat disease, and can even render the drug no longer useful. Biologics may be prescribed for the treatment of many different diseases and conditions, especially inflammatory diseases. If you are a candidate for treatment with a biologic medication, it is useful to know how anti-drug antibodies are monitored and prevented, as well as the effects they may have on your treatment.
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What Is a Biologic?
A biologic is a type of medication that is created inside a living cell, which can be from a human, an animal, or a microorganism. They are manufactured in a controlled, engineered environment.
The production and chemical composition of biologics are more complex than that of most medications. Biologics are large molecules, with a high molecular weight. They tend to be unstable and in many cases need to be kept refrigerated until they are used.
The manufacturing process for a biologic medication requires highly controlled conditions. Because of the challenges involved in their development, manufacture, and distribution, they tend to be very expensive.
It’s not possible to make exact copies of a biologic, so creating “generic” that is exactly the same as the original isn’t possible. It is possible to make a biologic that is similar to the original. These are called “biosimilars.”
Getting Started: What to Know About Biologics for Rheumatoid Arthritis
Biologics and Immune Response
Because biologics are created using living cells, they can trigger an unintended immune response in which the body forms anti-drug antibodies that actually “fight” the drug.
Almost all biologic medications can lead to the development of anti-drug antibodies, though the risk is different for each individual drug. This is true for biologics whether they are derived from human, animal, or microorganism sources. The anti-drug antibodies could make the drug less effective.
Effects and Management of Anti-Drug Antibodies
Solutions for this problem include the addition of a co-therapy, an increase in the drug dosage or frequency, or a change to a different drug altogether.
There are pros and cons to each solution. For example, if you take your biologic drug more often, there’s a potential for there to be too much of the drug in your system. And the cost is a limitation, as biologics tend to be expensive to manufacture and administer.
The Potential for Anti-Drug Antibodies
It’s not clear why some people develop these antibodies and others do not, although it may be due to genetic differences.
Researchers are trying to understand better why it happens, and how to treat it or avoid it in the first place. In some cases, other medications are given to try to prevent the immune response. Other strategies include slowing down the rate at which the drug is given during an infusion and doing regular blood tests to monitor the presence and/or level of anti-drug antibodies (called therapeutic drug monitoring).
Research on Prevalence
Not every biologic medication is associated with the same chance of creating antibodies, and it’s possible that certain immune diseases could result in different anti-drug antibody responses.
In one small study comparing three popular biologic medications, it was found that anti-drug antibodies were present in 42% of those receiving Remicade (infliximab), 33% of those receivingHumira (adalimumab), and in none of those patients receiving Enbrel (etanercept).
And a review of 443 studies was done to find out how often antibodies were present in patients who had rheumatoid arthritis and were treated with biologics. This review showed that antibodies were found in 0% to 85% of patients treated with Remicade, 0% to 54% of patients treated with Humira, 21 to 52% of patients treated with Remsima (which is also marketed as Inflectra, which are both biosimilars of Remicade), 0% to 1% of patients treated with Cosentyx (secukinumab), 1 to 11% of patients treated withStelara (ustekinumab), 0% to 13% of patients treated with Enbrel (etanercept), and 0% to 19% of patients treated withSimponi (golimumab).
Risks With Stopping and Restarting a Biologic
In some cases, you might stop receiving a biologic drug for a while. This is sometimes called a “drug holiday.”
Reasons for a drug holiday:
Loss of response to the biologic is also a reason for stopping a drug and switching to another type of therapy.
It might be possible to start the same drug again after a drug holiday, but there may be some considerations. Your doctor might monitor you to look for antibodies during the drug re-introduction.
There has been some research on re-starting a biologic after it stopped working the first time. In one study on patients with inflammatory bowel disease (IBD), Remicade was started after a drug holiday of about 15 months. The reasons for stopping were infusion reactions, pregnancy, or loss of response. The researchers found that while some patients who restarted did have infusion reactions, 70% of patients were still having a beneficial response one year after starting Remicade again along with an immunomodulator (such as 6-MP or azathioprine).
If you stopped taking a drug because of anti-drug antibodies or an infusion reaction, it might not always be possible to start that same drug again because there’s a risk of an adverse reaction or of the drug simply not working.
Therapeutic Drug Monitoring
With therapeutic drug monitoring, the drug level is considered when deciding whether to continue or stop these medications. The level of anti-drug antibodies is also an important factor.
A blood test can measure how much of a drug is in your system and if you have any anti-drug antibodies.
The Role of Steroids in Preventing Antibodies
The addition of methotrexate is considered key to preventing the development of anti-drug antibodies, particularly with Humira and Remicade.
In some cases, steroids (likeprednisone) are given before an injection or an infusion of a biologic medication. Steroids are given as a pre-medication for many people.
How Developing Antibodies Affects Future Treatment
In some cases, developing antibodies to one biologic medication could mean that there is a higher risk of developing antibodies to another biologic.
For instance, it was shown that patients with IBD who developed antibodies to Remicade were more likely to also develop antibodies to Humira. The researchers emphasize that this can help physicians and patients make informed decisions when it comes to switching medications.
A Word From Verywell
There are many considerations to keep in mind when you have an autoimmune disease. Make sure you tell your doctor about any symptoms you’re experiencing—they could be due to your disease or they could be side effects of treatment. If you develop anti-drug antibodies to the biologics you’re taking, you might need to have a modification of your therapeutic plan. There are still a lot of unknowns about anti-drug antibodies. Currently, there are guidelines for monitoring and for making changes in treatment when needed, and you can ask your medical team to help you understand the reasons for any adjustments.
How Biologic Therapy Works
11 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Felis-Giemza A, Moots RJ,Measurement of anti-drug antibodies to biologic drugs.Rheumatology.2015;54:1941–1943. doi:10.1093/rheumatology/kev279Sauna ZE.Immunogenicity of protein-based therapeutics. U.S. Food and Drug Administration. March 27, 2018.Kosmac M, Toplak N, Simonini G, et al.Anti-drug antibodies are associated with diminished drug levels and treatment failure (abstract).Arthritis Rheum.2012;64:2598.Quistrebert J, Hässler S, Bachelet D, et al.Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: A European retrospective multicohort analysis.Semin Arthritis Rheum. 2019;48(6):967‐975. doi:10.1016/j.semarthrit.2018.10.006Rubin DT.Restarting biologic agents after a drug holiday.Gastroenterol Hepatol (N Y).2019;15:612‐615.Baert F, Drobne D, Gils A, et al.Early trough levels and antibodies to infliximab predict safety and success of reinitiation of infliximab therapy.Clin Gastroenterol Hepatol. 2014;12(9):1474‐e91. doi:10.1016/j.cgh.2014.01.033Van Stappen T, Vande Casteele N, Van Assche G, Ferrante M, Vermeire S, Gils A.Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant assay: post hoc analysis of the TAXIT trial.Gut. 2018;67(5):818‐826. doi:10.1136/gutjnl-2016-313071Dalal SR, Cohen RD.What to do when biologic agents are not working in inflammatory bowel disease patients.Gastroenterol Hepatol (N Y).2015;11:657‐665.Bitoun S, Nocturne G, Ly B, Krzysiek R, Roques P, Pruvost A, Paoletti A, Pascaud J, Dönnes P, Florence K, Gleizes A, Hincelin-Mery A, Allez M, Hacein-Bey-Abina S, Mackay F, Pallardy M, Le Grand R, Mariette X.Methotrexate and BAFF interaction prevents immunization against TNF inhibitors.Ann Rheum Dis.2018 Oct;77(10):1463-1470. doi:10.1136/annrheumdis-2018-213403Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P.Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial.Gastroenterology. 2003;124:917‐924. doi:10.1053/gast.2003.50145Frederiksen MT, Ainsworth MA, Brynskov J, et al.Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.Inflamm Bowel Dis.2014;20:1714‐1721. doi:10.1097/MIB.0000000000000138Additional ReadingLiu A, Li Y, Yang H, Lv H, Qian J.Influence of previous corticosteroid treatment on the efficacy and safety of infliximab therapy in Crohn disease.Medicine (Baltimore). 2019;98(15):e15189. doi:10.1097/MD.0000000000015189Mantzaris GJ, Viazis N, Petraki K, et al.A pilot study comparing hydrocortisone premedication to concomitant azathioprine treatment in preventing loss of response to infliximab.Eur J Gastroenterol Hepatol. 2009;21:1042‐1048. doi:10.1097/MEG.0b013e32832937e3Moots RJ, Xavier RM, Mok CC, et al.The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.PLoS One.2017;12:e0175207. doi:10.1371/journal.pone.0175207Nanda KS, Cheifetz AS, Moss AC.Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (Ibd): A meta-analysis.Am J Gastro. 2013;108:40-47. doi:10.1038/ajg.2012.363
11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Felis-Giemza A, Moots RJ,Measurement of anti-drug antibodies to biologic drugs.Rheumatology.2015;54:1941–1943. doi:10.1093/rheumatology/kev279Sauna ZE.Immunogenicity of protein-based therapeutics. U.S. Food and Drug Administration. March 27, 2018.Kosmac M, Toplak N, Simonini G, et al.Anti-drug antibodies are associated with diminished drug levels and treatment failure (abstract).Arthritis Rheum.2012;64:2598.Quistrebert J, Hässler S, Bachelet D, et al.Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: A European retrospective multicohort analysis.Semin Arthritis Rheum. 2019;48(6):967‐975. doi:10.1016/j.semarthrit.2018.10.006Rubin DT.Restarting biologic agents after a drug holiday.Gastroenterol Hepatol (N Y).2019;15:612‐615.Baert F, Drobne D, Gils A, et al.Early trough levels and antibodies to infliximab predict safety and success of reinitiation of infliximab therapy.Clin Gastroenterol Hepatol. 2014;12(9):1474‐e91. doi:10.1016/j.cgh.2014.01.033Van Stappen T, Vande Casteele N, Van Assche G, Ferrante M, Vermeire S, Gils A.Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant assay: post hoc analysis of the TAXIT trial.Gut. 2018;67(5):818‐826. doi:10.1136/gutjnl-2016-313071Dalal SR, Cohen RD.What to do when biologic agents are not working in inflammatory bowel disease patients.Gastroenterol Hepatol (N Y).2015;11:657‐665.Bitoun S, Nocturne G, Ly B, Krzysiek R, Roques P, Pruvost A, Paoletti A, Pascaud J, Dönnes P, Florence K, Gleizes A, Hincelin-Mery A, Allez M, Hacein-Bey-Abina S, Mackay F, Pallardy M, Le Grand R, Mariette X.Methotrexate and BAFF interaction prevents immunization against TNF inhibitors.Ann Rheum Dis.2018 Oct;77(10):1463-1470. doi:10.1136/annrheumdis-2018-213403Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P.Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial.Gastroenterology. 2003;124:917‐924. doi:10.1053/gast.2003.50145Frederiksen MT, Ainsworth MA, Brynskov J, et al.Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.Inflamm Bowel Dis.2014;20:1714‐1721. doi:10.1097/MIB.0000000000000138Additional ReadingLiu A, Li Y, Yang H, Lv H, Qian J.Influence of previous corticosteroid treatment on the efficacy and safety of infliximab therapy in Crohn disease.Medicine (Baltimore). 2019;98(15):e15189. doi:10.1097/MD.0000000000015189Mantzaris GJ, Viazis N, Petraki K, et al.A pilot study comparing hydrocortisone premedication to concomitant azathioprine treatment in preventing loss of response to infliximab.Eur J Gastroenterol Hepatol. 2009;21:1042‐1048. doi:10.1097/MEG.0b013e32832937e3Moots RJ, Xavier RM, Mok CC, et al.The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.PLoS One.2017;12:e0175207. doi:10.1371/journal.pone.0175207Nanda KS, Cheifetz AS, Moss AC.Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (Ibd): A meta-analysis.Am J Gastro. 2013;108:40-47. doi:10.1038/ajg.2012.363
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Felis-Giemza A, Moots RJ,Measurement of anti-drug antibodies to biologic drugs.Rheumatology.2015;54:1941–1943. doi:10.1093/rheumatology/kev279Sauna ZE.Immunogenicity of protein-based therapeutics. U.S. Food and Drug Administration. March 27, 2018.Kosmac M, Toplak N, Simonini G, et al.Anti-drug antibodies are associated with diminished drug levels and treatment failure (abstract).Arthritis Rheum.2012;64:2598.Quistrebert J, Hässler S, Bachelet D, et al.Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: A European retrospective multicohort analysis.Semin Arthritis Rheum. 2019;48(6):967‐975. doi:10.1016/j.semarthrit.2018.10.006Rubin DT.Restarting biologic agents after a drug holiday.Gastroenterol Hepatol (N Y).2019;15:612‐615.Baert F, Drobne D, Gils A, et al.Early trough levels and antibodies to infliximab predict safety and success of reinitiation of infliximab therapy.Clin Gastroenterol Hepatol. 2014;12(9):1474‐e91. doi:10.1016/j.cgh.2014.01.033Van Stappen T, Vande Casteele N, Van Assche G, Ferrante M, Vermeire S, Gils A.Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant assay: post hoc analysis of the TAXIT trial.Gut. 2018;67(5):818‐826. doi:10.1136/gutjnl-2016-313071Dalal SR, Cohen RD.What to do when biologic agents are not working in inflammatory bowel disease patients.Gastroenterol Hepatol (N Y).2015;11:657‐665.Bitoun S, Nocturne G, Ly B, Krzysiek R, Roques P, Pruvost A, Paoletti A, Pascaud J, Dönnes P, Florence K, Gleizes A, Hincelin-Mery A, Allez M, Hacein-Bey-Abina S, Mackay F, Pallardy M, Le Grand R, Mariette X.Methotrexate and BAFF interaction prevents immunization against TNF inhibitors.Ann Rheum Dis.2018 Oct;77(10):1463-1470. doi:10.1136/annrheumdis-2018-213403Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P.Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial.Gastroenterology. 2003;124:917‐924. doi:10.1053/gast.2003.50145Frederiksen MT, Ainsworth MA, Brynskov J, et al.Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.Inflamm Bowel Dis.2014;20:1714‐1721. doi:10.1097/MIB.0000000000000138
Felis-Giemza A, Moots RJ,Measurement of anti-drug antibodies to biologic drugs.Rheumatology.2015;54:1941–1943. doi:10.1093/rheumatology/kev279
Sauna ZE.Immunogenicity of protein-based therapeutics. U.S. Food and Drug Administration. March 27, 2018.
Kosmac M, Toplak N, Simonini G, et al.Anti-drug antibodies are associated with diminished drug levels and treatment failure (abstract).Arthritis Rheum.2012;64:2598.
Quistrebert J, Hässler S, Bachelet D, et al.Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: A European retrospective multicohort analysis.Semin Arthritis Rheum. 2019;48(6):967‐975. doi:10.1016/j.semarthrit.2018.10.006
Rubin DT.Restarting biologic agents after a drug holiday.Gastroenterol Hepatol (N Y).2019;15:612‐615.
Baert F, Drobne D, Gils A, et al.Early trough levels and antibodies to infliximab predict safety and success of reinitiation of infliximab therapy.Clin Gastroenterol Hepatol. 2014;12(9):1474‐e91. doi:10.1016/j.cgh.2014.01.033
Van Stappen T, Vande Casteele N, Van Assche G, Ferrante M, Vermeire S, Gils A.Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant assay: post hoc analysis of the TAXIT trial.Gut. 2018;67(5):818‐826. doi:10.1136/gutjnl-2016-313071
Dalal SR, Cohen RD.What to do when biologic agents are not working in inflammatory bowel disease patients.Gastroenterol Hepatol (N Y).2015;11:657‐665.
Bitoun S, Nocturne G, Ly B, Krzysiek R, Roques P, Pruvost A, Paoletti A, Pascaud J, Dönnes P, Florence K, Gleizes A, Hincelin-Mery A, Allez M, Hacein-Bey-Abina S, Mackay F, Pallardy M, Le Grand R, Mariette X.Methotrexate and BAFF interaction prevents immunization against TNF inhibitors.Ann Rheum Dis.2018 Oct;77(10):1463-1470. doi:10.1136/annrheumdis-2018-213403
Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P.Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial.Gastroenterology. 2003;124:917‐924. doi:10.1053/gast.2003.50145
Frederiksen MT, Ainsworth MA, Brynskov J, et al.Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.Inflamm Bowel Dis.2014;20:1714‐1721. doi:10.1097/MIB.0000000000000138
Liu A, Li Y, Yang H, Lv H, Qian J.Influence of previous corticosteroid treatment on the efficacy and safety of infliximab therapy in Crohn disease.Medicine (Baltimore). 2019;98(15):e15189. doi:10.1097/MD.0000000000015189Mantzaris GJ, Viazis N, Petraki K, et al.A pilot study comparing hydrocortisone premedication to concomitant azathioprine treatment in preventing loss of response to infliximab.Eur J Gastroenterol Hepatol. 2009;21:1042‐1048. doi:10.1097/MEG.0b013e32832937e3Moots RJ, Xavier RM, Mok CC, et al.The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.PLoS One.2017;12:e0175207. doi:10.1371/journal.pone.0175207Nanda KS, Cheifetz AS, Moss AC.Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (Ibd): A meta-analysis.Am J Gastro. 2013;108:40-47. doi:10.1038/ajg.2012.363
Liu A, Li Y, Yang H, Lv H, Qian J.Influence of previous corticosteroid treatment on the efficacy and safety of infliximab therapy in Crohn disease.Medicine (Baltimore). 2019;98(15):e15189. doi:10.1097/MD.0000000000015189
Mantzaris GJ, Viazis N, Petraki K, et al.A pilot study comparing hydrocortisone premedication to concomitant azathioprine treatment in preventing loss of response to infliximab.Eur J Gastroenterol Hepatol. 2009;21:1042‐1048. doi:10.1097/MEG.0b013e32832937e3
Moots RJ, Xavier RM, Mok CC, et al.The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.PLoS One.2017;12:e0175207. doi:10.1371/journal.pone.0175207
Nanda KS, Cheifetz AS, Moss AC.Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (Ibd): A meta-analysis.Am J Gastro. 2013;108:40-47. doi:10.1038/ajg.2012.363
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