Worse Organ Damage Likely for Older Men With Diffuse SSc: Study

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Several clinical characteristics in people with systemic sclerosis (SSc) — specifically, being male, older age, diffuse SSc forms, and inflammation — were associated with a greater accumulation of organ damage over time in a recent study.

The level of damage accumulation, called a damage trajectory, also correlated with mortality rates, according to the research team.

“We identified three trajectories of damage accrual in a combined incident SSc cohort [group]. Several characteristics increased the odds of belonging to worse trajectories,” the team wrote, noting that patients with the worst trajectories “have already acquired more damage very early (within 2 years of disease onset).”

“These findings may be helpful in recognizing patients in whom early aggressive treatment is necessary,” they added.

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The study, “Damage Trajectories in Systemic Sclerosis Using Group-Based Trajectory Modeling,” was published in the journal Arthritis Care and Research.

SSc, also known as scleroderma, is characterized by immune dysregulation leading to excessive fibrosis (scarring) of the skin and other organs, which can lead to significant organ damage.

Led by Australian and Canadian scleroderma experts, researchers previously developed the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI) in an effort to measure levels of irreversible organ damage in SSc patients.

Now, the research team used the SCTC-DI to determine which SSc clinical features may contribute to worsening organ damage over time among 410 patients enrolled in the Canadian Scleroderma Research Group registry and the Australian Scleroderma Cohort Study. The participants had a disease duration of less than two years.

SCTC-DI scores were monitored over a mean follow-up period of three years, and sorted into three groups based on the level of damage observed, called damage trajectory groups. The groups were: low damage (224 people), medium damage (144 people), and high damage (42 people).

In the low damage group, the mean SCTC-DI at the start of the study (baseline) was 2.2. In the medium and high groups, baseline SCTC-DI scores were 5.5 and 10.1, respectively.

During the follow-up, participants in all three groups accumulated more damage than they had at the study’s start. However, those in the medium and high groups accrued damage at a significantly faster rate than those in the low group.

This difference was most notable in the cardiovascular and renal systems. Specifically, 21.4% of those in the high damage group had cardiovascular damage compared with 10.4% in the medium group and 1.8% of the low group. Renal damage occurred in 26.2%, 4.9%, and 0.5% of the high, medium, and low groups, respectively.

During the follow-up, more deaths were reported in the high damage trajectory group (23.8%) than in the medium (18.8%) or low (6.7%) groups.

“The observation that worse trajectories already had significantly more damage at baseline, which was within 2 years of disease onset, highlights that significant damage is accrued very early in the disease and that future rates of damage accrual and even mortality risk may be determined very early,” the researchers noted.

Several clinical characteristics at baseline were found to be associated with worse damage trajectories.

Specifically, male sex and older age increased the chances of being in a high damage trajectory, whereas Caucasian ethnicity decreased them.

Diffuse forms of SSc and the presence of tendon friction rubs — a disease feature associated with diffuse SSc — were associated with worse damage trajectories.  Levels of C-reactive protein (CRP), an inflammatory marker, were also associated with an increased likelihood of being in a high damage trajectory.

In contrast, anti-centromere antibodies, an indicator of SSc, were more prevalent in those with lower damage trajectories, which is consistent with previous reports.

“In conclusion, we have identified three distinct trajectories of damage accrual in a large international incident SSc cohort,” the researchers wrote.

Individuals in the worst trajectories — with evident early damage — were found to “continue to accrue damage at a faster rate in the next 3-4 years,” they noted.

“Given this is the first study to use the SCTC-DI, our findings further validate it as an important tool in research and clinical trials. Future studies are needed to explore the impact of different treatment modalities on damage accrual and to investigate ways to practically predict which trajectory an individual patient will fall into,” they concluded.