Pulmonary arterial hypertension in systemic lupus erythematosus may benefit by addition of immunosuppression to vasodilator therapy: an observational study

Kommireddy, Sirisha; Srinivas, B.; Kurimeti, Kishorebabu; Chennareddy, Srinivasa; Kanchinadham, S; Prasad, Irlapati Rajendra Vara; Rajasekhar, Liza

doi:10.1093/rheumatology/kev097

Cited by 51 publications

(40 citation statements)

References 18 publications

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“…Tanaka et al46 reported a significant reduction of RVSP in seven out of eight patients who received corticosteroids ± cyclophosphamide (CYC) – two patients relapsed and were again treated successfully. Intravenous CYC pulses (dose ranging from 500 mg/month to 1,000 mg/m 2 /month) were also administered in five cohort studies in conjunction with prednisone (0.5–1 mg/kg/day with slow tapering)47,48 and vasodilators49,50 or PDE5 inhibitors 51. Gonzalez-Lopez et al47 showed that CYC in combination with low doses of prednisone (<15 mg/day) was effective in 16 patients with moderate SLE-PAH as assessed by TTE.…”

Section: Therapeutic Approachmentioning

confidence: 99%

“…More recent studies demonstrated that the addition of vasodilators and supportive treatment with diuretics and anticoagulants may benefit patients with more severe PAH at diagnosis; in those studies, patients with MCTD were also included 49. Finally, Kommireddy et al51 reported a mean reduction of 16 mmHg in PASP (assessed by TTE) with three intravenous CYC pulses plus oral prednisone and PDE5 inhibitors in 11/24 patients with SLE-PAH. Moreover, rituximab was shown to provide benefit in a refractory case of SLE-PAH,52 while another patient was successfully managed with mycophenolate mofetil and cyclosporine 12.…”

Section: Therapeutic Approachmentioning

confidence: 99%

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Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

Tselios¹,

Gladman²,

Urowitz³

2016

OARRR

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Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram. Its pathogenesis is multifactorial with vasoconstriction, due to imbalance of vasoactive mediators, leading to hypoxia and impaired vascular remodeling, collagen deposition, and thrombosis of the pulmonary circulation. Multiple predictive factors have been recognized, such as Raynaud’s phenomenon, pleuritis, pericarditis, anti-ribonuclear protein, and antiphospholipid antibodies. Secure diagnosis is based on right heart catheterization, although transthoracic echocardiogram has been shown to be reliable for patient screening and follow-up. Data on treatment mostly come from uncontrolled observational studies and consist of immunosuppressive drugs, mainly corticosteroids and cyclophosphamide, as well as PAH-targeted approaches with endothelin receptor antagonists (bosentan), phosphodiesterase type 5 inhibitors (sildenafil), and vasodilators (epoprostenol). Prognosis is significantly affected, with 1- and 5-year survival estimated at 88% and 68%, respectively.

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Section: Therapeutic Approachmentioning

confidence: 99%

Section: Therapeutic Approachmentioning

confidence: 99%

Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

Tselios¹,

Gladman²,

Urowitz³

2016

OARRR

View full text Add to dashboard Cite

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“…86 Immunosuppressive therapy is routinely administered in patients with connective tissue disease associated with PAH and has been shown, in conjunction with vasodilators, in mostly observational studies to improve functional class and hemodynamics in patients with lupus and mixed connective tissue disease. 87,88 Several inflammatory and immune cell modulators including mycophenolate mofetil, leukotriene inhibitors, and anti-CD20 antibody have been investigated as therapeutics in PAH and demonstrated benefit in animal models. [89][90][91] Further studies and experimental models are needed to determine the benefit of pre-existing or novel therapeutics that target the different cell types involved in this immune/inflammatory disturbance.…”

Section: T-cells (Cd3+) Cytotoxic T-cells (Cd8+) and Helper T-cellsmentioning

confidence: 99%

Steps forward in the treatment of pulmonary arterial hypertension: latest developments and clinical opportunities

Badlam

Bull

2017

Therapeutic Advances in Chronic Disease

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Pulmonary arterial hypertension (PAH) is a chronic disease that results in narrowing of the small pre-capillary pulmonary arteries leading to elevation of pulmonary artery pressure and pulmonary vascular resistance, subsequent right ventricular failure, and if unchecked, death. Advances in the treatment of PAH over the last two decades have markedly improved survival. These improvements reflect a combination of changes in treatments, improved patient care strategies, and varying disease phenotypes in the PAH population. Currently approved therapies for PAH are directed at the recognized abnormalities within the pulmonary vasculature and include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin pathway agents. Most of these drugs have been approved on the basis of short-term trials that mainly demonstrated improvements in exercise capacity. More recently, long-term, event-driven trials of novel drugs have been performed, demonstrating new efficacy parameters. There have also been exciting advances in the understanding of right heart failure pathophysiology in PAH that have the potential to inspire the development of right ventricular targeted therapy and continued discoveries in the heterogeneity of disease and response to treatment has great potential for developing more 'personalized' therapeutic options. In this article, we review the current available data regarding the management of PAH, with an emphasis on the pharmacologic therapies and discussion of novel therapeutic directions for the treatment of this fatal disease.

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“…One of the most distinctive aspects of CTD‐PAH from other PAH is response to immunosuppression. Treatment combining glucocorticoids and intravenous cyclophosphamide (IVCY) may result in clinical improvement in patients with SLE‐, MCTD‐ or primary Sjögren's syndrome‐PAH but has failed to show response in those with SSc‐PAH . However, there is currently no answer on a case of overlap syndrome, such as patients who have both SSc and SLE.…”

Section: Role Of Immunosuppressionmentioning

confidence: 99%

“…However, there is currently no answer on a case of overlap syndrome, such as patients who have both SSc and SLE. Addition of immunosuppression to PAH‐specific vasodilator therapy may produce a further therapeutic effect in SLE‐PAH patients . Of note, vasodilator resistant case may also respond to immunosuppression .…”

Section: Role Of Immunosuppressionmentioning

confidence: 99%

Pulmonary arterial hypertension associated with connective tissue diseases: A review focusing on distinctive clinical aspects

Kato

Atsumi

2017

Eur J Clin Investigation

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Recent studies have clarified that pulmonary arterial hypertension associated with connective tissue diseases (CTD-PAH) has some distinctive clinical aspects from other PAH, such as high prevalence, venous and cardiac involvement, less favourable outcome, helpfulness of detection algorithm, response to immunosuppression, pre-PAH conditions in borderline pulmonary arterial pressure and coexistence of interstitial lung disease. In this review, by focusing on these distinctive aspects, we discuss how to provide an efficacious and safe management of CTD-PAH and garner attention to areas where further evidence is desired. K E Y W O R D Sconnective tissue diseases, pulmonary arterial hypertension, pulmonary hypertension, systemic lupus erythematosus, systemic sclerosis | INTRODUCTIONPulmonary hypertension (PH) is an increased blood pressure in pulmonary arteries and affects the right side of the heart, being diagnosed when the blood pressure in the circulation of the lung measured by right heart catheterization (RHC) is 25 mm Hg or greater. PH occurs as a consequence of remodelling and constriction of the pulmonary arteries and arterioles, called pulmonary arterial hypertension (PAH) and classified as group 1 PH; impaired left heart function and subsequent pulmonary vascular congestion, group 2 PH; hypoxia-mediated pulmonary vasoconstriction in the presence of lung diseases, group 3 PH; occlusion of the pulmonary vascular bed caused by thromboembolism, group 4 PH; or unclear multifactorial mechanisms, group 5 PH.1 Of these 5 forms of PH, PAH is of particular clinical significance because of its high mortality if left untreated and the recent advances in specific therapy including endothelin receptor antagonists (ERA), phosphodiesterase type 5 inhibitors (PDE5i), a soluble guanylate cyclase stimulator, prostacyclin analogues and a prostacyclin receptor agonist. Connective tissue diseases (CTD) are the major cause of PAH, occupying around one-fourth of the total PAH population. 2,3 PAH associated with CTD (CTD-PAH), compared with idiopathic PAH (IPAH), has some unique clinical characteristics, such as less favourable outcome, venous and cardiac involvement and response to immunosuppression. This review focuses on these CTD-PAH-specific aspects and discusses how to efficiently detect and diagnose PAH in CTD patients and to effectively treat CTD-PAH.

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Pulmonary arterial hypertension in systemic lupus erythematosus may benefit by addition of immunosuppression to vasodilator therapy: an observational study

Abstract: Immunosuppression and vasodilators produced significant improvement in SLE PAH over 6 months.

Cited by 51 publications

References 18 publications

Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

Steps forward in the treatment of pulmonary arterial hypertension: latest developments and clinical opportunities

Pulmonary arterial hypertension associated with connective tissue diseases: A review focusing on distinctive clinical aspects

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