De-escalation of biological therapy in inflammatory bowel disease: Benefits and risks

Abstract

Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting inflammation of the intestine, posing significant treatment challenges. Maintenance treatment with an immunomodulator (IM) and/or aminosalicylates is often required to reduce disease relapse in Crohn's disease (CD) and ulcerative colitis (UC). Despite adequate maintenance therapy, some patients experience disease flares that require escalation to biological therapy. [1,2] As there is currently no cure available for IBD, the treatment strategy for patients focuses on induction and maintenance of remission. As South Africa (SA) is a developing country and biological drug cost prohibitive, the (accelerated) step-up treatment strategy is used, with high-dose corticosteroids the favourite induction agent. This is followed by maintenance therapy with aminosalicylates or an IM to maintain remission. Examples of IM agents include azathioprine, 6-mercaptopurine and methotrexate. Thioguanine (Lanvis) is also used for severe IBD in an off-label setting in some centres. Patients who experience disease flares while receiving adequate doses of maintenance therapy and/or require a second course of high-dose corticosteroid therapy within a short treatment interval (usually 1 year), are escalated to biological therapy. Other indications for biological treatment include steroid-dependant and steroid-refractory disease. Since the launch of infliximab 20 years ago, the number of biological agents introduced to the market has grown exponentially, especially in the past decade. Currently available classes of biological agents for IBD in SA include: (i) tumour necrosis factor alpha (TNF alpha) antagonists, which include infliximab, adalimumab and golimumab; (ii) the integrin antagonist vedolizumab (Entyvio); and (iii) ustekinumab, a newly introduced interleukin (IL)-12 and IL-23 anta gonist (Stelara). [3-7] The last two agents are awaiting SA Health Products Regulatory Authority (SAHPRA) approval and currently only have limited availability on compassionate basis. Biological agents have revolutionised the treatment of IBD, especially over the past decade. A recent systematic review by Cote-Diagneault et al. [8] comprehensively summarised the success rate of IBD treatment with biologics. A detailed discussion of this topic is This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0. De-escalation of biological therapy in inflammatory bowel disease: Benefits and risks E Fredericks, 1 FCP (SA), Cert Gastroenterology (SA), PhD; G Watermeyer, 2 FCP (SA), Cert Gastroenterology (SA), MPH (SA)

Systematic review with meta‐analysis: the effects of immunomodulator or biological withdrawal from mono‐ or combination therapy in inflammatory bowel disease

“…51 The feasibility of therapy withdrawal after medically induced remission is a common scientific question, and several systematic reviews have recently addressed this issue. 7,15,30,[51][52][53] Firstly, we assessed the effect of withdrawal of IM monotherapy, where the results showed an almost twice as high chance of relapse at both 1 and 2 years after therapy withdrawal than with continued therapy. A twofold relapse rate was detected only in the CD subgroup but not in UC.…”

“…5,6 In clinical practice, three major classes of biologics are approved for IBD: tumour necrosis factor (TNF) alpha antagonists, integrin and interleukin-12/23 antagonists. 7 In addition to the assessment of the severity and activity of the disease, and to risk stratification, the optimal treatment decision involves individual and financial considerations. 8,9 The lifetime treatment strategy focuses not only on the induction and maintenance of remission but also on complete mucosal healing to prevent complications of the disease.…”

“…15 Several rationales for stopping treatment exist, such as reducing total health care costs, adverse events (AE) or serious adverse events (SAE), and patient-specific factors are also considered (eg adherence to treatment, life events [pregnancy, breastfeeding], long-lasting remission). 7 Recently, The European Crohn's and Colitis Organisation published a consensus on stopping treatment, called 'exit strategy'. 15 In UC patients with mild clinical course and complete mucosal healing, dose reduction in 5-aminosalicylates can be considered but 5-aminosalicylates should be continued in the long term to reduce the risk of relapse and colorectal cancer.…”

“…Biologic therapies have been available for more than 20 years to provide patients with moderate‐to‐severe disease with the best therapeutic option for the induction and maintenance of remission 5,6 . In clinical practice, three major classes of biologics are approved for IBD: tumour necrosis factor (TNF) alpha antagonists, integrin and interleukin‐12/23 antagonists 7 . In addition to the assessment of the severity and activity of the disease, and to risk stratification, the optimal treatment decision involves individual and financial considerations 8,9 .…”

“…Despite the consensus and guidelines for remission maintenance IBD therapies, our knowledge of withdrawing effective therapies in remission is uncertain 15 . Several rationales for stopping treatment exist, such as reducing total health care costs, adverse events (AE) or serious adverse events (SAE), and patient‐specific factors are also considered (eg adherence to treatment, life events [pregnancy, breastfeeding], long‐lasting remission) 7 …”