Existing physician global assessments of overall health, activity and damage used in systemic sclerosis (SSc) clinical trials are not directly interchangeable producing discordant results at least half the time, Australian research has found.
The findings provide a strong justification for efforts currently underway to standardise a SSc-specific physician global assessment (PhyGA), which would improve methodological rigour of SSc clinical trials, according to the researchers.
Their study compared the results from three different PhyGA instruments simultaneously applied among 1965 participants in the Australian Scleroderma Cohort Study.
Results showed that among the three rating scales, the direction of change of each PhyGA was concordant only 50% of the time, with patient-reported breathlessness the only metric associated with all three scores.
“These results suggest the physician assessment of each of these three constructs is informed by the assessment of different disease manifestations, and each PhyGA is likely to give complimentary rather than overlapping clinical information,” the researchers wrote in Arthritis Care & Research (link here).
“This has implications when considering the use of the PhyGA in RCTs.”
Change in physician-assessed activity scores was also associated with patient-reported worsening skin disease (OR 1.25) and faecal incontinence (OR 1.23).
On the other hand, damage scores were associated with respiratory disease such as pulmonary arterial hypertension and COPD, as well as skin scores and faecal incontinence.
Led by senior author Professor Mandana Nikpour, a rheumatologist at Royal Prince Alfred Hospital Sydney and the University of Sydney, the team noted the significant clinical heterogeneity in SSc presentation had created challenges in overall disease assessment, possibly accounting for the discordance of PhyGA results.
“These results suggest that when presented with multiple PhyGA instruments each targeting an individual disease construct such as activity, damage and overall disease, physicians are adjusting their overall assessment,” they wrote.
“The lack of concordance between results of each of the PhyGA instruments indicates that when PhyGA questions are worded differently or are addressing different disease constructs, results are not directly comparable and should be each be considered as individual instruments rather than directly compared as results of ‘the physician global’.”
GI manifestations common in SSc
Meanwhile, data from the same cohort study indicate gastrointestinal tract manifestations are affecting almost 90% of Australian SSc patients, and negatively impacting QoL and physical function.
Patients with severe GI symptoms and severe diarrhoea were also more likely to be unemployed, although manifestations were not directly associated with increased mortality, the researchers said.
The study included 907 consecutive patients from the Australian Scleroderma Cohort Study who had prospectively completed the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 questionnaire (UCLA GIT) between 2015 and 2021.
Some 87% reported experiencing at least on GI symptom, with 46-52% reporting moderate to very severe symptoms of reflux, distension, diarrhoea and constipation.
Higher UCLA GIT scores were also significantly associated with worse QoL, physical function, fatigue, anxiety and depression, the researchers found.
But reflux and distension were the symptoms with the strongest correlation with poor QoL and physical function, they reported in Arthritis Care & Research (link here).
“Our study highlights the substantial burden associated with GIT symptoms in terms of QoL, physical function, mental health and employment in SSc,” they wrote.
“It makes a compelling case for investing more resources in understanding the pathophysiology of GIT involvement and finding novel efficacious treatments.”
The majority of participants’ UCLA GIT scores did not change over time, noted the authors, who theorised this may be due to the prevalent patient population used.
“The majority of our patients were not incident cases with an average disease duration of around 14 years,” they wrote.
“Accordingly, in this cohort, GIT symptoms may represent pre-existing damage rather than disease activity.”