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SSc patients with pre-capillary hypertension benefit from targeted DMARDs

Presented by
Dr Cosimo Bruni, University Hospital Zurich, Switzerland
EULAR 2023

Not immunosuppressive therapy per se, but treatment with targeted therapy demonstrated a significant protective effect on mortality or worsening in patients with systemic sclerosis (SSc) and pre-capillary pulmonary hypertension (precapPH). As these new results are based on registry data, randomised-controlled trials are now suggested for further evaluation.

A retrospective observational study was performed to gain insight into the possible benefit of targeted DMARDs on precapPH-complicating SSc [1]. SSc patients from the EUSTAR registry with data on their immunosuppressive therapy and results from a right heart catheter that fulfilled the haemodynamic criteria for precapPH were included. The analysis focussed on death or a predefined worsening of precapPH as the outcome, comparing patients with or without immunosuppressants. It also took into account a wide variety of potentially confounding covariates regarding risk stratification, among them gender, age, lung function, cardiac insufficiency markers, renal history, and medication levels.

Out of 755 patients, 82% were women, the mean age was 63 years, 29% had diffuse cutaneous SSc, and SSc with precapPH was present over a mean of 11 years. Half were treated with immunosuppressants, and 94% in this group had ≥1 conventional synthetic DMARD.

After a follow-up of 2.9 years, 72% had either died or experienced an event of pulmonary worsening. “These events were numerically higher in the immunosuppressants-exposed group, both for the combined outcome or for the separate (death or precapPH worsening) outcomes,” Dr Cosimo Bruni (University Hospital Zurich, Switzerland) described.

Primarily, the Cox-regression modelling failed to find significance in the effect of immunosuppressants overall (P=0.551). However, after stratification according to the type of treatment, targeted therapy demonstrated a significant effect (P=0.021) on protection against the combined outcome of death or precapPH worsening. As the presence or absence of interstitial lung disease (ILD) might have influenced this result, a further categorisation was performed that again yielded significance for targeted therapies (P=0.026), confirming that the effect was independent of ILD. “The signals that we noted were mostly related to tocilizumab, having a statistically significant protective effect, and a trend was also noted for rituximab,” Dr Bruni further specified.

“Now, randomised clinical trials exploring targeted therapies should be designed using long-term morbidity and mortality outcomes to validate our results further and possibly improve the care of our patients,” Dr Bruni recommended in his conclusion.

  1. Bruni C. Immunosuppression with targeted DMARDS reduces morbidity and mortality in pre-capillary pulmonary hypertension associated with systemic sclerosis: a EUSTAR analysis. OP0238, EULAR 2023, 31 May–3 June, Milan, Italy.

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