To STRIDE or not to STRIDE: a critique of “treat to target” in Crohn´s disease

ABSTRACT

Introduction

The STRIDE consensus suggested to focus on mucosal healing, based on biomarkers and endoscopy, in addition to clinical endpoints as treatment target. This narrative review provides a critique of this concept in Crohn´s disease.

Areas covered

We analyze and discuss the limitations of endpoints as targets, their currently limited achievability, and the controversial evidence relating to ‘treat to target.’ The relevant publications in Pubmed were identified in a literature review with the key word ‘Crohn´s disease.’

Expert opinion

All targets and endpoints have their limitations, and, even if reached, not all have unequivocally been shown to improve prognosis. The major deficiency of STRIDE is not only the lack of validation and agreement upon endpoints but little evidence of their achievability in a sizable proportion of patients by dose or timing adjustments or switching the medication. Above all, the concept should be based on clear evidence that patients indeed benefit from appropriate escalation of treatment and relevant controlled studies in this regard have been controversial. Until the STRIDE approach is proven to be superior to standard treatment focusing on clinical well-being, the field should remain reluctant and expect more convincing evidence before new targets are approved.

KEYWORDS:

• Crohn´s disease
• therapy
• endpoints
• biologicals
• janus-kinase inhibitors

Article highlights

• The STRIDE concept promised to revolutionize the way how IBD should be treated by going beyond the standard target of clinical response/remission toward the new target of mucosal healing, based on endoscopy and biomarkers.

• However, there is disagreement on the optimal endpoint definitions to serve as targets. This applies not only to clinical but also endoscopic, histological, transmural and other endpoints.

• In the majority of patients endoscopic, histological, and transmural endpoints are not reached by current treatments.

• Furthermore, in case the primary medication (usually anti-TNF) failed, the effect of second line alternatives is substantially worse than first line treatment and patients may even loose clinical remission following a drug switch.

• Important studies designed to support this approach were controversial, i.e. standard treatment is not clearly superior to ‘treat to target.’

• Thus, evidence and, consequently, acceptance of the ‘treat to target’ approach based on endoscopy and biomarkers is limited. Since routine repeated endoscopy is not practical, detailed studies on bowel ultrasound as a conjunct endpoint are justified and may in the future substantiate treatment decisions.

Declaration of interest

KR Herrlinger has received honoraria for consulting Amgen, travel sup- port from Janssen and speaker’s honoraria from Falk Pharma. EF Stange has received honoraria for consulting Amgen, CureVac, Dr. Falk Pharma, Janssen, Merck und Takeda and has given lectures supported by AbbVie, Dr. Falk Pharma, Ferring, Janssen and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.