Fecal Transplant Doesn’t Help Systemic Sclerosis GI Symptoms

TOPLINE:

Fecal microbiota transplantation with anaerobic cultivated human intestinal microbiome (ACHIM) was well tolerated in patients with systemic sclerosis but showed no significant improvement over placebo in relieving gastrointestinal (GI) symptoms.

METHODOLOGY:

• This phase 2 clinical trial studied the effects of repeated upper intestinal infusions of ACHIM vs placebo in adult patients with systemic sclerosis and moderate to severe lower GI tract symptoms.
• It enrolled 67 participants (mean age, 58.91 years; 93% women) who underwent a screening phase for 4-12 weeks and were stratified on the basis of their worst symptom at the time of screening (bloating or diarrhea).
• The participants were then randomly assigned in a 1:1 ratio to receive intestinal infusions of either ACHIM (n = 33) or placebo (n = 34) at weeks 0 and 2.
• The primary outcome was the change in the worst lower GI tract symptom from week 0 to week 12, assessed using the University of California, Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 scoring system.
• Safety was assessed at weeks 0, 2, 4, 6, and 12 in all participants who received at least one infusion.

TAKEAWAY:

• Changes in the worst lower GI tract symptom from baseline to week 12 were not significantly different between the ACHIM and placebo groups (average marginal effect [AME], 0.20; P = .22).
• Subgroup analysis of participants with a disease duration less than 3 years showed a trend toward improvement with ACHIM compared with placebo (AME, −0.70; P = .08).
• Adverse events were reported by 16 (48%) participants receiving ACHIM and 19 (56%) participants receiving placebo; most adverse events were mild and short-lived.
• Microbiota analysis revealed increased abundance of specific bacterial species in the ACHIM group compared with placebo, even though there was a lack of change in microbial alpha and beta diversity between the groups.

IN PRACTICE:

“Selecting a predominant systemic sclerosis–associated gastrointestinal tract symptom and tailoring the fecal microbiota transplantation to the most affected gastrointestinal site could yield more promising results,” experts wrote in an accompanying comment. “[But] for now, we conclude that fecal microbiota transplantation is not quite ready for prime time but holds promise for the future with refinement of trial design.”

SOURCE:

This study was led by Håvard Fretheim, PhD, Oslo University Hospital, Oslo, Norway. It was published online on January 31, 2025, in The Lancet Rheumatology.

LIMITATIONS:

An unexpected improvement in symptoms from screening to study initiation was observed, which may have complicated the identification of significant symptom improvements during the study. The weekly questionnaire format might have been less effective for capturing disease activity than the daily assessments. The study population primarily comprised women with long-standing disease and positive anticentromere antibodies, potentially limiting generalizability.

DISCLOSURES:

This study received funding from KLINBEFORSK. One author reported being one of the co-founders of ACHIM Biotherapeutics AB and having shares in the company. Several other authors reported serving as speakers; holding leadership or fiduciary roles; and receiving grants, research funding, consulting fees, honoraria, and other ties with various pharmaceutical companies and institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.