Dose tailoring of anti‐tumour necrosis factor‐alpha therapy delivers useful clinical efficacy in <scp>C</scp>rohn disease patients experiencing loss of response

Ghaly, Simon; Beswick, Lauren; Pudipeddi, Aviv; Agarwal, Ashish; Sechi, Alexandra; Antoniades, Sally; Headon, Belinda; Connor, Susan J.; Lawrance, Ian C.; Sparrow, Miles P.; Walsh, Alissa J.; Andrews, Jane M.

doi:10.1111/imj.12621

Cited by 7 publications

(25 citation statements)

References 19 publications

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“…Response rates ranged from 33% to 100% (Figure 2), and remission was achieved in 15% to 83% of patients at any point after treatment escalation 10,23‐41 . In 15 of these studies, more than half of the patients regained clinical response after dose escalation 23‐25,27‐32,35‐39,42 . In the study by Narula et al, 31 only one (7.1%) of the 14 anti‐TNF naïve patients escalated to 40 mg weekly achieved clinical remission at the end of follow‐up.…”

Section: Resultsmentioning

confidence: 99%

“…The majority of clinical efficacy data were from retrospective studies with subcohorts that underwent empiric dose escalation (without the use of TDM) for loss of response to standard treatment. Twenty studies reported clinical outcomes following empiric escalation of maintenance adalimumab 10,23‐41 . Response rates ranged from 33% to 100% (Figure 2), and remission was achieved in 15% to 83% of patients at any point after treatment escalation 10,23‐41 .…”

Section: Resultsmentioning

confidence: 99%

“…In the Suzuki et al trial, 49 baseline CDAI <220 did not predict clinical remission at 40 weeks after dose escalation ( P = 0.116). The absence of prolonged steroid use was associated with sustained steroid‐free remission after dose escalation in one study, 28 while the need for concurrent steroids at anti‐TNF induction predicted nonresponse to dose escalation in another study 30 …”

Section: Resultsmentioning

confidence: 99%

“…10,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Response rates ranged from 33% to 100% (Figure 2), and remission was achieved in 15% to 83% of patients at any point after treatment escalation. 10,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] In 15 of these studies, more than half of the patients regained clinical response after dose escalation. [23][24][25][27][28][29][30][31][32]…”

Section: Standard Maintenance Dosing Of Infliximab and Adalimumabmentioning

confidence: 99%

“…For infliximab, rates of clinical response and remission following empiric escalation for treatment failure ranged from 34% to 90% and 26% to 81%, respectively, across 12 studies (Figure 3). 28,[31][32][33][43][44][45][46][47][48][49][50] In eight of these studies, intensified therapy recaptured response in over 50% of the patients. 28,36,[45][46][47][48][49][50] In one retrospective study (n = 265), a switch to adalimumab achieved numerically higher rates of clinical response (83.3%) than infliximab dose escalation (42.3%).…”

Section: Standard Maintenance Dosing Of Infliximab and Adalimumabmentioning

confidence: 99%

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Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

Mattoo

Basnayake

Connell

et al. 2021

Aliment Pharmacol Ther

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Summary Background Loss of response to anti‐TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD). Aims To perform a systematic review assessing the efficacy of escalated maintenance anti‐TNF therapy in CD. Methods EMBASE, MEDLINE, Web of Science, and CENTRAL databases were searched for English language publications through to April 25, 2021. Full‐text articles evaluating escalated maintenance treatment (infliximab or adalimumab) in adult CD patients were included. Results A total of 4733 records were identified, and 68 articles met eligibility criteria. Rates of clinical response (33%‐100%) and remission (15%‐83%) after empiric dose escalation for loss of response to standard anti‐TNF therapy were high but varied across studies. Dose intensification strategies (doubling the dose versus shortening the therapeutic interval) were similarly efficacious. Dose‐escalated patients tended to have higher serum drug levels compared to those on standard dosing. An exposure‐response relationship following dose escalation was found in a number of observational studies. Randomised controlled trials comparing therapeutic drug monitoring (TDM) to empiric treatment intensification have failed to reach their primary end‐points. Strategies including Bayesian dashboard‐dosing and early treatment escalation targeting biomarker normalisation were found to be associated with improved long‐term outcomes. Conclusions Empiric escalation of maintenance anti‐TNF therapy can recapture clinical response in a majority of patients with secondary loss of response to standard maintenance doses. Proactive optimisation of maintenance dosing might prolong time to loss of response in some patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Standard Maintenance Dosing Of Infliximab and Adalimumabmentioning

confidence: 99%

Section: Standard Maintenance Dosing Of Infliximab and Adalimumabmentioning

confidence: 99%

See 3 more Smart Citations

Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

Mattoo

Basnayake

Connell

et al. 2021

Aliment Pharmacol Ther

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Treatment escalation and de-escalation decisions in Crohn’s disease: Delphi consensus recommendations from Japan, 2021

et al. 2023

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Background We aimed to develop criteria for treatment intensification in patients with (1) luminal Crohn’s disease (CD), (2) CD with perianal disease and/or fistula, (3) CD with small bowel stenosis, (4) in the postoperative setting, and (5) for discontinuing or reducing the dose of treatment in patients with CD. Methods PubMed and Embase were searched for studies published since 1998 which may be relevant to the five defined topics. Results were assessed for relevant studies, with preference given to data from randomized, controlled studies. For each question, a core panel of 12 gastroenterologists defined the treatment target and developed statements, based on the literature, current guidelines, and relevant additional studies. The evidence supporting each statement was graded using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). A modified Delphi process was used to refine statements and gain agreement from 54 Japanese specialists at in-person and online meetings conducted between October 2020 and April 2021. Results Seventeen statements were developed for treatment intensification in luminal CD (targeting endoscopic remission), six statements for treatment intensification in perianal/fistulizing CD (targeting healing of perianal lesions and complete closure of the fistula), six statements for treatment intensification in CD with small bowel stenosis (targeting resolution of obstructive symptoms), seven statements for treatment intensification after surgery (targeting endoscopic remission), and five statements for discontinuing or reducing the dose of treatment in patients with CD. Conclusions These statements provide guidance on how and when to intensify or de-intensify treatment for a broad spectrum of patients with CD.

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Dose Escalation Patterns of Advanced Therapies in Crohn’s Disease and Ulcerative Colitis: A Systematic Literature Review

et al. 2023

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Introduction Dose escalation is one of the treatment approaches studied and suggested in advanced therapies for Crohn’s disease (CD) and ulcerative colitis (UC). This study aimed to identify and characterize the dosing escalation patterns of advanced therapies in CD and UC. Methods Two systematic literature reviews (SLRs) were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE ® , Embase ® , and Cochrane Library were searched for articles published between January 2011 and October 2021 and limited to non-interventional studies in English language. Congress and bibliographic searches were also conducted. Articles were screened by two independent researchers. Dose escalation patterns were described and summarized considering the regional regulatory label recommendation (in North America [NA] or outside of North America [ONA]). Results Among 3190 CD and 2116 UC articles identified in the Ovid searches, 100 CD and 54 UC studies were included in the SLR, with more studies conducted ONA. Most studies reported an initial maintenance dose pattern aligned with the lower starting dose per local regulatory label; however, several ONA studies ( n = 13 out of 14) reported ustekinumab every 8 weeks as starting maintenance pattern in CD. In ONA studies, the median within-guideline escalation rates in CD and UC were 43% in ustekinumab (CD only), 33% and 32% for vedolizumab; 29% and 39% for adalimumab; and 14% and 10% for infliximab. Evidence regarding dose escalation patterns for tofacitinib, certolizumab pegol, and golimumab was limited. Some dose escalation patterns outside of label recommendations were observed including ustekinumab every 8 weeks to every 4 weeks and vedolizumab every 8 weeks to every 6 weeks. Conclusion Dose escalation strategies are widely documented in the literature. The reported dose escalation patterns and escalation rates vary by region and by CD and UC. Most escalation patterns reported were aligned with regulatory recommendations while some reported more diverse or aggressive dose escalation. Prospero Registration CRD42021289251. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02457-6.

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Dose tailoring of anti‐tumour necrosis factor‐alpha therapy delivers useful clinical efficacy in Crohn disease patients experiencing loss of response

Abstract: Short-term dose tailoring regains disease response in the majority of patients with CD. Of these, most will remain free of corticosteroids at 1 year after de-escalating therapy.

Cited by 7 publications

References 19 publications

Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

Systematic review: efficacy of escalated maintenance anti‐tumour necrosis factor therapy in Crohn's disease

Treatment escalation and de-escalation decisions in Crohn’s disease: Delphi consensus recommendations from Japan, 2021

Dose Escalation Patterns of Advanced Therapies in Crohn’s Disease and Ulcerative Colitis: A Systematic Literature Review

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