The incidence rate of pulmonary arterial hypertension and scleroderma renal crisis in systemic sclerosis patients with digital ulcers on endothelin antagonist receptors (ERAs) and phosphodiesterase-5 inhibitors (PDE5i)

Rheumatology (Oxford). 2021 Feb 1;60(2):872-880. doi: 10.1093/rheumatology/keaa401.

Abstract

Introduction: Endothelin antagonist receptors (ERAs) and phosphodiesterase-5 inhibitors (PDE5i) are beneficial in pulmonary arterial hypertension (PAH) and digital ulcers (DU) and prevent from DU recurrences. Our study aimed to determine the difference in the incidence rate of PAH and scleroderma renal crisis (SRC) in patients with SSc and DU (SSc-DU) under ERAs/PDE5i or without treatment.

Methods: We conducted a retrospective cohort study including SSc-DU patients from the Spanish Scleroderma Registry (RESCLE). The primary outcome was the incidence rate of PAH and SRC in patients under ERAs/PDE5i or not.

Results: Some 544 patients out of 1817 (29.9%) in the RESCLE database had DU, 221 (40.6%) under ERAs/PDE5i and 323 (59.4%) not. The incidence rate (95% CI) difference between patients under treatment or not under did not reach statistical significance in PAH [-0.1 (-4.8, 4.69), P = 0.988] or in SRC [0.7 (-2.2, 3.7), P = 0.620]. However, the time from the first DU to the diagnosis of SRC was delayed in treated patients [mean (s.d.) 7.6 (5.8) years vs 2.9 (5.3); P = 0.021]. The dcSSc subset was more prevalent in the treatment group (36 vs 26%; P = 0.018), along with anti-topoisomerase I antibodies (34 vs 18%; P < 0.001) and tendon friction rubs (12 vs 6%; P = 0.038), whereas the lcSSc subset was more prevalent in the no-treatment group (57 vs 66%; P = 0.031) along with ACA (37 vs 46%; P = 0.031).

Conclusion: There was no difference in the incidence rate of PAH and SRC between groups. However, treatment with ERAs and/or PDE5i appeared to delay the occurrence of SRC.

Keywords: endothelin antagonist receptors; phosphodiesterase-5 inhibitors; prevention; pulmonary arterial hypertension; scleroderma renal crisis; treatment.

MeSH terms

  • Acute Kidney Injury* / epidemiology
  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / prevention & control
  • Blood Vessels / drug effects
  • Endothelin Receptor Antagonists / therapeutic use*
  • Female
  • Fingers
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Pulmonary Arterial Hypertension* / diagnosis
  • Pulmonary Arterial Hypertension* / epidemiology
  • Pulmonary Arterial Hypertension* / etiology
  • Pulmonary Arterial Hypertension* / prevention & control
  • Registries / statistics & numerical data
  • Scleroderma, Systemic* / drug therapy
  • Scleroderma, Systemic* / epidemiology
  • Scleroderma, Systemic* / physiopathology
  • Skin Ulcer* / diagnosis
  • Skin Ulcer* / epidemiology
  • Skin Ulcer* / etiology
  • Skin Ulcer* / prevention & control
  • Spain / epidemiology
  • Treatment Outcome

Substances

  • Endothelin Receptor Antagonists
  • Phosphodiesterase 5 Inhibitors