Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease
Anti-tumor necrosis factor (anti-TNF) therapy has been successfully used as first-line biologic treatment for moderate-to-severe inflammatory bowel disease (IBD), in both “step-up” and “top-down” approaches, and has become a cornerstone of IBD management. However, in a proportion of patients the eff...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.897936/full |
| _version_ | 1817968259772710912 |
|---|---|
| author | Jan Marsal Jan Marsal Manuel Barreiro-de Acosta Irina Blumenstein Maria Cappello Thomas Bazin Shaji Sebastian |
| author_facet | Jan Marsal Jan Marsal Manuel Barreiro-de Acosta Irina Blumenstein Maria Cappello Thomas Bazin Shaji Sebastian |
| author_sort | Jan Marsal |
| collection | DOAJ |
| description | Anti-tumor necrosis factor (anti-TNF) therapy has been successfully used as first-line biologic treatment for moderate-to-severe inflammatory bowel disease (IBD), in both “step-up” and “top-down” approaches, and has become a cornerstone of IBD management. However, in a proportion of patients the effectiveness of anti-TNF therapy is sub-optimal. Either patients do not achieve adequate initial response (primary non-response) or they lose response after initial success (loss of response). Therapeutic drug monitoring determines drug serum concentrations and the presence of anti-drug antibodies (ADAbs) and can help guide treatment optimization to improve patient outcomes. For patients with low drug concentrations who are ADAb-negative or display low levels of ADAbs, dose escalation is recommended. Should response remain unchanged following dose optimization the question whether to switch within class (anti-TNF) or out of class (different mechanism of action) arises. If ADAb levels are high and the patient has previously benefited from anti-TNF therapy, then switching within class is a viable option as ADAbs are molecule specific. Addition of an immunomodulator may lead to a decrease in ADAbs and a regaining of response in a proportion of patients. If a patient does not achieve a robust therapeutic response with an initial anti-TNF despite adequate drug levels, then switching out of class is appropriate. In conjunction with the guidance above, other factors including patient preference, age, comorbidities, disease phenotype, extra-intestinal manifestations, and treatment costs need to be factored into the treatment decision. In this review we discuss current evidence in this field and provide guidance on therapeutic decision-making in clinical situations. |
| first_indexed | 2024-04-13T20:05:42Z |
| format | Article |
| id | doaj.art-18c3d1619cc44446ab85ae39a2e8f065 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-13T20:05:42Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-18c3d1619cc44446ab85ae39a2e8f0652022-12-22T02:31:59ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-06-01910.3389/fmed.2022.897936897936Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel DiseaseJan Marsal0Jan Marsal1Manuel Barreiro-de Acosta2Irina Blumenstein3Maria Cappello4Thomas Bazin5Shaji Sebastian6Department of Gastroenterology, Skåne University Hospital, Lund/Malmö, SwedenDepartment of Immunology, Lund University, Lund, SwedenGastroenterology Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Internal Medicine 1, Gastroenterology, Hepatology and Clinical Nutrition, University Clinic Frankfurt, Frankfurt, GermanyGastroenterology and Hepatology Section, Promise, University of Palermo, Palermo, ItalyDepartment of Gastroenterology, Université Paris Saclay/UVSQ, INSERM, Infection and Inflammation, UMR 1173, AP-HP, Hôpital Ambroise Paré, Boulogne Billancourt, FranceInflammatory Bowel Disease (IBD) Unit, Hull University Teaching Hospitals National Health Service (NHS) Trust, Hull, United KingdomAnti-tumor necrosis factor (anti-TNF) therapy has been successfully used as first-line biologic treatment for moderate-to-severe inflammatory bowel disease (IBD), in both “step-up” and “top-down” approaches, and has become a cornerstone of IBD management. However, in a proportion of patients the effectiveness of anti-TNF therapy is sub-optimal. Either patients do not achieve adequate initial response (primary non-response) or they lose response after initial success (loss of response). Therapeutic drug monitoring determines drug serum concentrations and the presence of anti-drug antibodies (ADAbs) and can help guide treatment optimization to improve patient outcomes. For patients with low drug concentrations who are ADAb-negative or display low levels of ADAbs, dose escalation is recommended. Should response remain unchanged following dose optimization the question whether to switch within class (anti-TNF) or out of class (different mechanism of action) arises. If ADAb levels are high and the patient has previously benefited from anti-TNF therapy, then switching within class is a viable option as ADAbs are molecule specific. Addition of an immunomodulator may lead to a decrease in ADAbs and a regaining of response in a proportion of patients. If a patient does not achieve a robust therapeutic response with an initial anti-TNF despite adequate drug levels, then switching out of class is appropriate. In conjunction with the guidance above, other factors including patient preference, age, comorbidities, disease phenotype, extra-intestinal manifestations, and treatment costs need to be factored into the treatment decision. In this review we discuss current evidence in this field and provide guidance on therapeutic decision-making in clinical situations.https://www.frontiersin.org/articles/10.3389/fmed.2022.897936/fullanti-TNFloss of responseprimary non-responseswitch out of classswitch within classtherapeutic drug monitoring |
| spellingShingle | Jan Marsal Jan Marsal Manuel Barreiro-de Acosta Irina Blumenstein Maria Cappello Thomas Bazin Shaji Sebastian Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease Frontiers in Medicine anti-TNF loss of response primary non-response switch out of class switch within class therapeutic drug monitoring |
| title | Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease |
| title_full | Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease |
| title_fullStr | Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease |
| title_full_unstemmed | Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease |
| title_short | Management of Non-response and Loss of Response to Anti-tumor Necrosis Factor Therapy in Inflammatory Bowel Disease |
| title_sort | management of non response and loss of response to anti tumor necrosis factor therapy in inflammatory bowel disease |
| topic | anti-TNF loss of response primary non-response switch out of class switch within class therapeutic drug monitoring |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.897936/full |
| work_keys_str_mv | AT janmarsal managementofnonresponseandlossofresponsetoantitumornecrosisfactortherapyininflammatoryboweldisease AT janmarsal managementofnonresponseandlossofresponsetoantitumornecrosisfactortherapyininflammatoryboweldisease AT manuelbarreirodeacosta managementofnonresponseandlossofresponsetoantitumornecrosisfactortherapyininflammatoryboweldisease AT irinablumenstein managementofnonresponseandlossofresponsetoantitumornecrosisfactortherapyininflammatoryboweldisease AT mariacappello managementofnonresponseandlossofresponsetoantitumornecrosisfactortherapyininflammatoryboweldisease AT thomasbazin managementofnonresponseandlossofresponsetoantitumornecrosisfactortherapyininflammatoryboweldisease AT shajisebastian managementofnonresponseandlossofresponsetoantitumornecrosisfactortherapyininflammatoryboweldisease |