Tobacco Linked To Worsening GI Symptoms, Not Some SSc Medicines

Patients with persistent symptoms used more healthcare resources, researchers said

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Tobacco use by systemic sclerosis (SSc) patients is linked to worsening gastrointestinal (GI) symptoms, but the immunosuppressive and anti-scarring medications used to treat the autoimmune disease aren’t, according to a recent analysis of data from a multicenter, U.S.-based patient registry.

The findings are striking in light of previous studies that suggested certain medications might drive GI problems in SSc patients, whereas tobacco hasn’t yet been linked to this type of symptom, noted Sarah Luebker, a doctor of osteopathic medicine, the study’s first author ,and a rheumatology fellow at Vanderbilt University Medical Center.

“It’s surprising that medications commonly blamed for gastrointestinal tract symptoms did not actually result in symptomology,” Luebker said in a press release from the American College of Rheumatology (ACR).

The researchers also found that patients with persistently severe GI symptoms over time generally used more healthcare resources, including doctor appointments, diagnostic tests, and hospital stays.

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The findings will be presented at the ACR Convergence 2022, ACR’s annual meeting, Nov. 10–14, in Philadelphia.

The buildup of scar tissue, or fibrosis, in SSc can broadly affect the body’s tissues, including the skin, lungs, heart, kidneys, and GI tract. GI involvement — the leading manifestation of SSc other than the skin — can cause significant daily life disruptions for patients, but may get overlooked in the clinic.

Gastrointestinal symptoms in SSc

Moreover, GI problems in SSc may be driven by multiple factors. While the disease itself can cause these types of symptoms, takinig SSc-specific medications may result in side effects that impact the GI system.

Luebker and her colleagues in the U.S. examined data from patients participating in the Collaborative National Quality and Efficacy Registry (CONQUER) to learn more about the natural history of GI symptoms in SSc and the potential links with health resource use by them.

CONQUER, launched by the Scleroderma Research Foundation in 2018, tracks adults with SSc starting within five years of their first symptoms. Patients are recruited at 17 large scleroderma centers in the U.S.

It’s surprising that medications commonly blamed for gastrointestinal tract symptoms did not actually result in symptomology.

As of May 4, 397 participants had completed a minimum of two of the serial Scleroderma Clinical Trials Consortium University of California Los Angeles Gastrointestinal Tract Questionnaire (GIT 2.0) and were included in the analysis.

GIT 2.0, a validated measure of GI involvement that occurred in the most recent week, measures reflux, bloating, diarrhea, constipation, and fecal incontinence, as well as the emotional and social impact of symptoms.

Most patients were women (83.4%) and white (80.6%). Their mean age at first visit was 51.7, and they had been living with the disease for a mean of 4.8 years.

A little more than half the participants (207 people, 52.1%) had mild GI symptoms that remained stable over time. The remaining patients had either severe, but stable symptoms (63 people; 15.9%), or had symptoms that improved (58 people; 14.6%) or worsened (69 people; 17.4%) between the first evaluation and a subsequent one.

Patients who had a change in GI symptom severity “did so within the first year of enrollment in CONQUER,” the researchers wrote.

Use of medications and GI symptoms

In a poster, titled “The Collaborative National Quality and Efficacy Registry for Scleroderma: Association of Medication Use on Gastrointestinal Tract Symptoms in Early Disease,” the researchers evaluated the relationship between medication use and GI symptoms among CONQUER participants.

Across all groups, patients using medications for reflux, or immunomodulatory (hydroxychloroquine) or immunosuppressive treatments, typically started treatment before the first study visit, while the anti-fibrotic medication Ofev (nintedanib) was started at or after that visit. No patient was on intravenous immunoglobulin (IVIG) therapy or Esbriet (pirfenidone), another anti-scarring medication.

GI symptom worsening over time was generally unrelated to SSc type, SSc-related antibody status, or use of immunomodulating, immunosuppressive, or anti-fibrotic medications. However, weight loss, reflux, use of medications to stimulate bowel movements, and current tobacco use were significantly associated with higher odds of GI symptom worsening.

The observed link with tobacco use — which raised the risk of GI symptom worsening by more than four times — is perhaps the “most fascinating” find, Luebker said, adding that “this has never been described before and highlights the value of tobacco cessation education.”

In another poster, titled “The Collaborative National Quality and Efficacy Registry for Scleroderma: Association of Resource Utilization and Gastrointestinal Tract Symptoms in Early Disease,” the researchers showed that patients with stable, severe GI symptoms over time also utilize significantly more healthcare resources.

Specifically, those patients required more visits with healthcare professionals, diagnostic tests related to GI involvement (colonoscopy and endoscopy), mobility aids, and inpatient hospitalizations.

“Improvement in [GI] symptoms can result in less resource utilization and is an important focus for CONQUER,” the researchers wrote, noting the presentations highlight the benefits of the CONQUER platform. Luebker called for its continued use on behalf of SSc patients.