Association Between the Occurrence of a Clinical RElapse and Gut MIcrobiota Modifications: a Cohort Study of Patients With pSOriasis (REMISSIOn)

The human microbiota corresponds to an extremely rich and varied set of microorganisms that colonize our various epitheliums from birth, including the intestine, lungs and skin, where they interact continuously with our immune system. Changes in microbial composition and function, termed dysbiosis, have been linked to alterations in immune responses and to disease development, such as psoriasis. Recent research has shown that the gut microbiota can condition the therapeutic response to checkpoint inhibitors and that fecal microbiota transplant overcomes resistance to these therapy, suggesting a direct role for the microbiota in the ability to shape a therapeutic immune response. Antibiotic exposure during the course of cancer therapy negatively correlates with patients' response to anti-PD-1 treatment response, thus highlighting the link between the enrichment of specific microbial taxa in intestines and the response to immunotherapy. This observation suggests that treatments capable of modulating microbial networks and promoting specific bacterial clades may modulate the host's immune response. Hence, beyond their expected effect in the targeted tissue, part of the therapeutic effect of drugs could rely on this mechanism. In psoriasis patients, observational studies suggest that gut microbiome is altered differently after the use of anti-IL17 or anti-IL23 biologic agents.

Main objective: To determine the evolution of microbial composition of fecal samples issued to patients who responded to a biologic agent (IL-17 inhibitors, IL-23 inhibitors) and have stopped their treatment for 2 to 4 weeks before the index date, at baseline and 6 months or clinical relapse after treatment discontinuation

Design of the study: Prospective french multicentre observational cohort study

Population of study participants: Patients with psoriasis in remission after IL23i or IL17inhibitor treatments and who have stopped their medication for 2 to 4 weeks.

Number of participants included: 50 adult patients considered in remission and have stopped for at least 2 weeks and a maximum of 4 weeks, one of the following biologic agent: secukinumab, ixekizumab, brodalumab, bimekizumab, guselkumab, tildrakizumab, or risankizumab

Study Overview

• Status: Not yet recruiting
• Conditions: Psoriasis; Microbial Colonization
• Intervention / Treatment: Other: Fecal sampling; Other: Blood sampling

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Mélanie Rousseaux; Phone Number: 0033 01 40 27 57 24; Email: melanie.rousseaux@aphp.fr
• Study Contact Backup: Name: Pierre-André NATELLA, PharmD; Phone Number: 0033 01 49 81 37 98; Email: pierre.natella@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients with psoriasis in remission after IL23i or IL17inhibitor treatments and who have stopped their medication for 2 to 4 weeks.

Description

Inclusion Criteria:

• Subject over 18 years of age
• Subject diagnosed with psoriasis considered in remission (as defined by absolute PASI<2 within 6 months of follow-up)
• Subject who has stopped his biologic agent including IL-17 inhibitors or IL-23 inhibitors for 2 to 4 weeks.
• Written informed consent for participation in the study

Exclusion Criteria:

• Subject currently experiencing or having a history of other concomitant skin conditions that would interfere with evaluation of psoriasis
• Subject treated by NSAIDs, antibiotics, antifungals, antivirals or proton-pump inhibitors within 4 weeks before inclusion (or foreseeable use during the study)
• Subject with a concomitant diagnosis of cirrhosis, coeliac disease or signs of bacterial infection
• Subject has concurrent acute or chronic viral hepatitis B or C or human immunodeficiency virus (HIV) infection
• Subject having a personal or familial history of psoriatic arthritis or inflammatory bowel disease
• Subject with BMI<18.5 or BMI>35
• Subject consuming probiotics or using specific diet with many dietary exclusions according to the discretion of the investigator
• Pregnant and /or breastfeeding woman,
• Subject deprived of liberty by judicial or administrative decision or patient under guardianship
• Subject unable to understand the purpose and conditions of the study and unable to give consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with psoriasis in remission; Patients with psoriasis in remission after IL23i or IL17inhibitor treatments and who have stopped their medication for 2 to 4 weeks.

Other: Fecal sampling; Stool samples are a collection of products derived from the human body that is not invasive in any way and samples not taken as part of usual care. Stool samples will be collected at home within 7 days of the visit M0, M3 and M6 and within 14 days of the visit M12 in an ethanol tube and in DNA/RNA shield, and transported at room temperature to Saint-Antoine Hospital (CRB SAT, AP-HP, Pr. SIMON ), samples will be aliquoted (3 aliquots per tubes) and stored at -80°C for a period of 5 years (renewable) At the end of the research, stool samples will be analysed using metagenomics sequencing. DNA extraction will be performed following the standards of the The International Human Microbiome Standards . DNA will be stored at -80°C.; Other Names: Stool samples; Other: Blood sampling; Blood samples (serum, 15 ml) are an additional and minimal collection performed following a sample taken as part of usual care. Blood samples (serum) will be collected during the visit at M0, M3 (± 7 days), M6 (± 7 days) and M12 (± 7 days). In the hours following collection, the samples must be aliquoted and stored at -80°C in a secure place in the participating centre.; Other Names: Blood samples (serum)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbial features	Microbial features (gene richness, species, functional modules) impacted by the discontinuation of the biologic agent after 6 months or the first occurrence of psoriasis clinical relapse.	after 6 months of the baseline visit or the first occurrence of psoriasis clinical relapse after baseline visit

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Emilie Sbidian, MD-PhD, APHP

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: September 20, 2023
• First Submitted That Met QC Criteria: September 20, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: microbiota; pSOriasis; anti-IL17 biologic agents; anti-IL23 biologic agents
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Disease Attributes; Skin Diseases, Papulosquamous; Infections; Communicable Diseases; Psoriasis
• Other Study ID Numbers: APHP230758

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No