Studies Drug/design Patients and baseline characteristics Outcome Intensive Immunosuppressive therapy (IIT) trials IIT: IV cyclophosphamide + oral glucocorticoids + vasodilator therapy (VT)
(i) 8 patients with SLE-aPAH IIT:
(ii) MPAP = 39.5 ± 9.2 (i) Significantly decreased MPAP
(iii) PVR = 8.75 ± 5.43 (ii) Tended to decrease PVR Miyamichi-Yamamoto et al. [19 ]
(iv) NYHA FC = I, II, III (iii) Normalized hemodynamics in a few patients.
(v) 6MWD = 442 ± 54 IIT + VT improved the pulmonary hemodynamics and long-term prognosis of patients with CTD-aPAH. Observational cohort study from a single center with historical control
(vi) Age = 42 ± 8 IIT: IV cyclophosphamide + glucocorticoids + VT Rx with IIT Rx with IIT + VT (i) SLE-aPAH patients with less severe disease may respond to treatment with IIT. N = 139 V (ii) For patients with more severe disease, VT should be started, possibly in combination with IIT. MPAP 48 ± 12 58 ± 10 Jais et al. [20 ] PVR 8.6 ± 3.5 14.3 ± 1.3 (iii) These retrospective and uncontrolled data need to be confirmed by randomized controlled trials. Retrospective, uncontrolled study NYHA II, III III, IV FC 6MWD 347 ± 80 381 ± 71 Age 31 ± 10 38 ± 9 IV cyclophosphamide
glucocorticoids
(i) 13 patients with SLE-aPAH (i) Of the responders [R] 62% had SLE.
(ii) MPAP (avg.) = 54 (ii) R’s had a significantly improved 6MWD and hemodynamic parameters. Sanchez et al. [21 ] Retrospective study
(iii) PVR (avg.) = 19
(iv) NYHA FC = II, III
iii
R’s had a better survival than non responders [NR].
(v) 6MWD (avg.) = 370
(vi) Age (avg.) = 29 Oral agents: endothelin receptor antagonists (ETRAs) and phosphodiesterase-5-inhibitors (PDE-5-I) Sildenafil 20 mg, 40 mg, 80 mg
(i) 19 patients with SLE-aPAH In patients with PAH-aCTD, sildenafil improves exercise capacity, hemodynamic parameters (at the 20 mg dose), and NYHA FC after 12 weeks of treatment.
(ii) MPAP = 47 ± 11 Badesch et al. [22 ] 12 week, double-blind study (SUPER-1)
(iii) PVR = 10.13 ± 5.45
(iv) NYHA FC = II, III, IV
(v) 6MWD = 342 ± 76
(vi) Age = 53 ± 15 Sildenafil 20 mg, 40 mg, 80 mg
(i) 19 patients with SLE Sildenafil improves exercise capacity and hemodynamics in patients with symptomatic PAH. SLE-aPAH subgroup analysis was not done.
(ii) MPAP = 52.75 ± 14 Galiè et al. [23 ] Double-blind placebo-controlled trial
(iii) PVR = 11.95 ± 6.29
(iv) NYHA FC = II, III, IV
(v) 6MWD = 344 ± 82
(vi) Age = 49 ± 15 Bosentan
(i) 16 patients with SLE
(ii) MPAP = 55 ± 16 Statistically significant improvement in exercise capacity, NYHA FC and increase in time to clinical worsening. Rubin et al. [24 ] Double-blind placebo-controlled
(iii) PVR = 12.68 ± 8.48 trial
(iv) NYHA FC = III, IV
(v) 6MWD = 330 ± 74
(vi) Age = 49 ± 16 Subcutaneous, inhaled, and intravenous prostanoids Subcutaneous treprostinil
(i) 25 patients with SLE
(ii) MPAP = 52 ± 2 Improved exercise capacity, dyspnea fatigue symptoms, hemodynamics and trend toward improved quality of life. Oudiz et al. [25 ]
(iii) NYHA FC = II, III, IV Double-blind placebo-controlled trial
(iv) 6MWD = 280 ± 13
(v) Age = 54 ± 2 Inhaled Iloprost
(i) 35 patients with CTD (i) Statistically significant benefit in combined endpoint of 10% improvement in 6MWD and FC improvement and absence of clinical deterioration. Olschewski et al. [26 ]
(ii) MPAP = 52.8 ± 11.5 Randomized placebo-controlled trial
(iii) PVR = 12.86 ± 4.88
(iv) NYHA FC = III, IV
(v) 6MWD = 332 ± 93
(vi) Age = 51 ± 13 (ii) No subgroup analysis done for SLE. Intravenous epoprostenol
(i) 6 patients with SLE Dramatic improvement in FC and marked improvement in hemodynamics.
(ii) MPAP = 57 ± 9 Robbins et al. [27 ] Case series
(iii) PVR = 14 ± 7
(iv) NYHA FC = III, IV
(v) Age = 26–35
