New Study Highlights Gaps in Patient-Reported Outcomes for Cutaneous Chronic GVHD, Calls for Disease-Specific Measures to Improve Clinical Trials

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A new study published by JAMA Dermatology illustrates the significant impact of cutaneous chronic graft-vs-host disease (GVHD) on patient health-related quality-of-life (HRQOL), along with finding gaps in existing patient-reported outcome (PROs) measures. As such, the study authors call for the development of a novel, disease-specific PRO to target these gaps and improve efficacy assessments in clinical trials.¹

“Despite the immense burden on patients, the [National Institutes of Health (NIH)] skin score, a clinician-reported measure of disease activity that encompasses body surface area involvement and depth of sclerosis, is the current reference-standard outcome measure used in chronic GVHD clinical trials,” the study authors wrote. “However, patients often have different perceptions of what is important compared with their clinicians and patient- and clinician-reported disease severity can be discordant. To gauge the efficacy of treatments in clinical trials, validated measurement of both clinician- and patient-focused outcomes is imperative.”¹

GvHD is a complication that follows an allogeneic transplant, in which hematopoietic stem cells transplanted from a donor into your body become mature blood cells. After transplantation, the body produces new blood cells from the donated stem cells. The new cells may identify the recipient’s body as foreign and begin attacking. Chronic GVHD can manifest at any time following an allogenic transplant, but typically begins within two years, commonly affecting the skin, mouth, liver, lungs, gastrointestinal tract, muscles, joints, or genitals.²

The study authors noted that skin is the organ that is most frequently affected by chronic GVHD, with 80% of patients requiring systemic therapy.¹

“In accordance with recommendations from the US Food and Drug Administration (FDA), concept elicitation using qualitative research is a critical first step to understand outcomes that are important to patients to develop and select patient-reported outcomes (PROs) with face validity,” the study authors wrote. “Qualitative data exploring chronic GVHD demonstrated multifaceted impacts on HRQOL domains, but a 2020 systematic review highlighted a lack of in-depth qualitative research exploring cutaneous chronic GVHD specifically.”

As such, the study sought to explore concept elicitation to define HRQOL in cutaneous chronic GVHD by gathering patient input to compare the lived experience of disease between patients with epidermal and sclerotic disease manifestations.

Study Design

Investigators performed a single-center qualitative analysis using open-ended, semi structured interviews and free-listing terms. Patients in the study were aged 18 years or older and had been diagnosed with active cutaneous chronic GVHD. An inductive analysis of the semi structured interviews gathered patient perspectives of living with cutaneous chronic GVHD to identify HRQOL domains and codes. Investigators used Smith salience index (Smith S) score to measure saliency for each list term, which was calculated from free-listing terms from the deidentified interviews.

In total, investigators interviewed 31 patients with cutaneous chronic GVHD (median [IQR] age, 61.1 [52.9-68.7] years), of whom 17 (54.8%) were male and 14 (45.2%) were female. Among these patients, nine (29.0%) had epidermal GVHD, 13 (41.9%) had sclerotic GVHD, and nine (29.0%) had a combination of disease types. Investigators identified 40 codes of importance within the five HRQOL domains, which consisted of skin changes and symptoms, social functioning, psychological and emotional functioning, physical functioning, and general health perceptions.

The most frequently reported symptoms of the condition were dry skin (n = 20 [65%]), tight skin (n = 19 [61%]), itch (n = 15 [48%]), and discoloration (n = 14 [45%]), with impaired social functioning reported by all patients in the trial. The most noteworthy symptoms patients identified were psychological and emotional functioning, which included frustration (Smith S score, 0.32) and worry or concern (Smith S score, 0.12), as well as symptoms that included discomfort (Smith S score, 0.20).

“PROs are important measures of therapeutic efficacy and are central components of the FDA’s patient-focused drug development program,” the study authors concluded. “According to FDA guidance, the development of a PRO must start with concept elicitation to understand patient perspectives and ensure content validity. This qualitative analysis identified symptoms, functions, and general health impacts relevant to patients with both epidermal and sclerotic chronic GVHD, many of which are not represented in existing PROs. Next steps will be to build on the present findings and the conceptual framework of HRQOL by developing a disease-specific PRO to use in clinical trials and as a clinical decision-making tool for cutaneous chronic GVHD.”¹

References

1. Baumrin E, Cronholm PF, Kearney MD, et al. Outcomes of Importance to Patients Living With Cutaneous Chronic Graft-vs-Host Disease. JAMA Dermatol. Published online January 02, 2025. doi:10.1001/jamadermatol.2024.5380

2. 2. Graft vs. Host Disease. Cleveland Clinic. Webpage. Updated February 21, 2023. Accessed January 3, 2025. https://my.clevelandclinic.org/health/diseases/10255-graft-vs-host-disease-an-overview-in-bone-marrow-transplant