Authors' objectives: The purpose of this report is to summarize the evidence regarding the clinical effectiveness and cost-effectiveness of PDE5 inhibitors for the treatment of secondary RP and/or digital ulcers secondary to another medical condition. Evidence-based guidelines with recommendations regarding pharmacological therapy for patients with secondary RP and/or digital ulcers secondary to another medical condition will also be reviewed.

Authors' results and conclusions: As a first-line therapy for the treatment of secondary Raynaud phenomenon (RP), phosphodiesterase type 5 (PDE5) inhibitors are more effective than a placebo at reducing the frequency, severity, and the duration of RP attacks. PDE5 inhibitors were less effective than calcium channel blockers or selective serotonin reuptake inhibitors at reducing the severity of RP attacks. Patients treated with PDE5 inhibitors were more likely to experience an adverse event and to discontinue treatment compared with those treated with a placebo. As a first-line therapy for the treatment of secondary digital ulcers, treatment with PDE5 inhibitors was less effective at preventing new digital ulcers than treatment with an endothelin receptor antagonist, but there was no difference in the time to healing or the size of the primary digital ulcer (findings based on 1 non-randomized study). There is a lack of evidence on the clinical effectiveness of PDE5 inhibitors as second-line therapy (i.e., after failed treatment with calcium channel blockers) for treating secondary RP and/or digital ulcers. There is a lack of evidence on the cost-effectiveness of PDE5 inhibitors for treating secondary RP and/or digital ulcers. Two guidelines were identified that provide recommendations for treating RP secondary to systemic sclerosis. Two guidelines recommend calcium channel blockers as first-line therapy based on high-quality evidence; 1 guideline recommends angiotensin II receptor antagonists as first-line therapy, but this is based on weak evidence. The guidelines also include recommendations that PDE5 inhibitors, selective serotonin reuptake inhibitors, alpha blockers, and statin therapy be considered for treating RP secondary to systemic sclerosis. For severe cases of RP secondary to systemic sclerosis, IV iloprost is recommended. Three guidelines were identified that provide recommendations for treating digital ulcers secondary to systemic sclerosis. Three guidelines recommend treatment with PDE5 inhibitors. The guidelines also recommend considering treatment with endothelin receptor antagonists, IV iloprost, and calcium channel blockers. For severe digital ulcers secondary to systemic sclerosis, treatment with IV iloprost or a PDE5 inhibitor is recommended. A patient with lived experience with secondary RP and digital ulcers was involved in this report, and they identified outcomes that are important to patients with secondary RP and/or digital ulcers. These outcomes included pain, digit loss, fatigue, mental health, and function. None of the studies or guidelines in this report included direct measures of these patient-identified outcomes.

Project Status: Completed

URL for project: https://www.cadth.ca/phosphodiesterase-5-inhibitors-treatment-secondary-raynauds-phenomenon-and-digital-ulcers

Year Published: 2021

URL for published report: https://www.cadth.ca/sites/default/files/pdf/htis/2021/RD0061%20PDE5%20inhibitors%20Final.pdf

English language abstract: An English language summary is available

Publication Type: Rapid Review

Country: Canada

Province: Ontario

Organisation Name: Canadian Agency for Drugs and Technologies in Health

Contact Address: 600-865 Carling Avenue, Ottawa, ON K1S 5S8 Canada. Tel: +1 613 226 2553; Fax: +1 613 226 5392;

Contact Name: requests@cadth.ca

Contact Email: requests@cadth.ca

Copyright: <p>Canadian Agency for Drugs and Technologies in Health (CADTH)</p>