Addition of thiopurines can recapture response in patients with <scp>C</scp>rohn's disease who have lost response to anti‐tumor necrosis factor monotherapy

Ong, David; Kamm, Michael A.; Hartono, Juanda Leo; Lust, Mark

doi:10.1111/jgh.12263

Cited by 40 publications

(23 citation statements)

References 26 publications

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“…In addition, it has recently been published that thiopurine – infliximab cotherapy in Crohn's disease patients is associated with reduced antibody formation, regardless of initial thiopurine therapeutic effect . Recapture of clinical response upon addition of an immunomodulator has also been reported among adalimumab therapy patients, who had previously failed immunomodulators, although immunogenicity and drug levels have not been evaluated in these reports.…”

Section: Discussionmentioning

confidence: 99%

Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab

Ungar

Kopylov

Engel

et al. 2016

Aliment Pharmacol Ther

108

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Summary Background Anti‐adalimumab antibodies (AAA) are associated with loss of clinical response (LOR). Addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy. Similar data on adalimumab are lacking. Aim To study the impact of immunomodulator addition on the emergence of AAA and LOR among adalimumab therapy patients. Methods The databases of three tertiary medical centres were reviewed to identify patients who developed AAA during adalimumab monotherapy with resultant LOR, and received an immunomodulator as a salvage combination therapy. All sera were prospectively analysed using previously described ELISA assays. Clinical response was determined using appropriate clinical scores. Elimination of AAA, designated as ‘sero‐reversal’, elevation of drug levels and regained clinical response were the sought outcomes. Results Twenty‐three patients (21 Crohn's disease, and 2 ulcerative colitis) developed AAA with subsequent LOR and were thereafter prescribed an immunomodulator as salvage therapy (thiopurine n = 14, methotrexate n = 9). Eleven patients (48%) underwent sero‐reversal with gradual elimination of AAA, increase in drug trough levels and restoration of clinical response (median time to sero‐reversal 5 months). In 12 patients (52%), immunogenicity and loss of response could not be reversed. There was no difference between responders and nonresponders in the type of immunomodulators used or baseline clinical characteristics. Conclusions In almost half of inflammatory bowel disease patients developing anti‐adalimumab antibodies and loss of response, established immunogenicity of adalimumab can be gradually reversed by the addition of immunomodulator therapy with restoration of a clinico‐biological response. However, these observations need to be confirmed with larger studies.

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Section: Discussionmentioning

confidence: 99%

Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab

Ungar

Kopylov

Engel

et al. 2016

Aliment Pharmacol Ther

108

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“…164 165 However, infliximab rescue therapy may be even less efficacious in hospital inpatients with more severe, steroid refractory disease, with 90 day colectomy rates reported as 29-60%. [155][156][157][158][159][160][161][162][163][164][165][166][167][168] A cohort study of 115 patients found that standard three dose infliximab induction was associated with lower rates of clinical response (70% v 41%; P=0.004), clinical remission (41% v 17%; P=0.015), and endoscopic remission (26% v 4%; P=0.046) in patients with severe ulcerative colitis than in those with only moderately severe disease. 155 Similarly, patients with severe ulcerative colitis who did not respond to infliximab induction had significantly more fecal loss of drug, 169 and lower day 14 trough levels 170 compared with infliximab responders.…”

Section: Skin Lesionsmentioning

confidence: 99%

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

Cohen

Sachar

2017

BMJ

115

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The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs. New and emerging treatments such as anti-attractants, anti-interleukins, and Janus kinase (JAK) inhibitors will also be discussed.

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“…Similarly to infliximab, additional pharmacokinetic studies showed that antibodies to adalimumab predicted Crohn's disease recurrence [52]. As well, adding an immunomodulator for combination therapy may recapture response to adalimumab [53]. With multiple approved and available antiTNFa antibodies, it is common that patients will have treatment with several agents within the class.…”

Section: Currently Available Therapeutic Antibodies In Digestive Disementioning

confidence: 99%

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

Sofia

Rubin

2017

Dig Dis Sci

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The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

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Addition of thiopurines can recapture response in patients with Crohn's disease who have lost response to anti‐tumor necrosis factor monotherapy

Abstract: Addition of a thiopurine in patients who have lost response to anti-TNF monotherapy is an effective strategy to recapture response even if the patient has previously failed thiopurine therapy. Thiopurines may reduce immunogenicity or act synergistically with anti-TNF therapy.

Cited by 40 publications

References 26 publications

Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab

Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

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