Clinical Outcome Measures in Raynaud’s Phenomenon

Raynaud’s phenomenon (RP) is a major cause of morbidity, resulting in pain, numbness, impaired hand function, emotional distress, decreased social participation, isolation and reduced health-related quality of life. This is particularly the case in systemic sclerosis (SSc) in which RP can be severe and occurs in virtually all patients. RP has been extensively studied in clinical trial settings but, given the importance of RP in SSc, most of these trials have included (either in mixed population or exclusively) patients with SSc. The clinical assessment of RP is challenging in warm ambient clinic settings owing to the specific relationship between RP symptoms and cold exposure and emotional stress. Quantification of the uniquely personal impact and severity of RP symptoms has, therefore, relied upon the usage of patient-reported outcome (PRO) instruments. A broad range of instruments have been devised that include global assessments of RP impact/severity and instruments assessing specific aspects of RP symptoms. Many of these instruments were developed for SSc-RP but have been used in primary RP and other forms of secondary RP. Diary-based approaches to assessing RP ‘attack’ characteristics have been the most commonly used endpoints in RP clinical trials over the last 25 years. Demonstrating net treatment efficacy of promising vasodilator therapies in controlled trial settings using traditional RP trial endpoints has been challenging, leading to recent efforts to devise novel PRO instruments grounded in the patient experience of RP. This chapter shall discuss the different PRO instruments used as clinical outcome measures for RP, their utility in the clinic setting and implications for future clinical trials of RP, particularly in the context of SSc.