Raynaud Condition Score Research Articles

Points to consider-Raynaud's phenomenon in systemic sclerosis.

RP is an exaggerated vasospastic response to cold or emotion. Randomized, double-blind, placebo-controlled trials with either parallel group or cross-over trials should be mainly considered. Cross-over design, which is good for early phase trials of immediate or very short-term outcomes, is important in a condition as heterogeneous as RP: a wash-out period between treatment arms should always be included to minimize the possibility of a period (carry-over) effect. Duration of RP trials is usually constrained by the need to complete these over a single season, usually winter when the weather is colder. For cross-over trials, each treatment arm tends to be 4 weeks or less. Frequency and duration of attacks, and the Raynaud's Condition Score are widely used outcome measures. There is increasing interest in physiological laboratory endpoints, for example laser Doppler imaging at least for early phase trials.

The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated Raynaud's Phenomenon: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

To assess the therapeutic efficacy of local injections of botulinum toxin type A (Btx-A) in improving blood flow to the hands of patients with Raynaud's phenomenon (RP) secondary to scleroderma. In this randomized, double-blind, placebo-controlled clinical trial, patients with scleroderma-associated RP received Btx-A (50 units in 2.5 ml sterile saline) in one randomly selected hand and sterile saline (2.5 ml) in the opposite hand. Follow-up at 1 and 4 months postinjection included laser Doppler imaging of hands, patient-reported outcomes, and physical examination. We compared outcomes using paired t-tests and population-average generalized models with generalized estimating equations. Of 40 patients enrolled, 25 had limited scleroderma and 15 had diffuse scleroderma. From baseline to 1-month follow-up, there was a greater reduction in average blood flow in Btx-A-treated hands compared to placebo-treated hands. The model estimated that this difference was statistically significant (average difference -30.08 flux units [95% confidence interval -56.19, -3.98], P for interaction = 0.024). This difference was mainly influenced by patients with longstanding RP and diffuse scleroderma. Change in blood flow at 4-month follow-up was not significantly different between groups. Clinical measures (QuickDASH, McCabe Cold Sensitivity Score, pain on a visual analog scale, and Raynaud's Condition Score) improved slightly for Btx-A-treated hands. Our laboratory-based laser Doppler imaging flow data do not support using Btx-A to treat RP in all scleroderma patients. The secondary clinical outcomes suggest some positive effect, but its clinical meaningfulness is questionable. The role of Btx-A in treating RP should be further studied with more homogeneous patient populations and in unique clinical situations such as acute digital ischemia.

Long-term follow-up after autologous adipose-derived stromal vascular fraction injection into fingers in systemic sclerosis patients

IntroductionHand involvement confers a substantial handicap in work and daily activities in patients with Systemic sclerosis (SSc). Autologous adipose-derived stromal vascular fraction is as an easily accessible source of cells with regenerative effects. We previously performed a phase I open-label clinical trial (NTC01813279) assessing the safety of subcutaneous injection of autologous adipose-derived stromal vascular fraction. Six and 12-month data have been reported. As patients were followed in our medical centre, we report their longer-term outcome beyond the end of the trial. Patients and methodTwelve females, mean age 54.5±10.3 years, initially enrolled in the clinical trial were assessed during a scheduled medical care, which took place between 22 and 30months after treatment. ResultsMultiple patient-reported outcomes showed sustained improvement, in comparison with the assessment performed just before surgery: 62.5% in the Cochin Hand Function Scale, 51.1% in the Scleroderma Health Assessment Questionnaire, 33.1% in hand pain, and 88.3% in the Raynaud Condition Score. A decrease in the number of digital ulcers number was noted. Mobility, strength and fibrosis of the hand also showed improvement. None of the 8 patients who had previously received iloprost infusion required new infusion. ConclusionDespite the limits of an open label study, the data are in favour of the long-term safety of the adipose-derived stromal vascular fraction injection. Two randomized double blind, placebo-controlled trials of this therapeutic agent are ongoing in the USA (NCT02396238) and in France (NCT02558543) and will help determine the place of this innovative therapy for SSc patients.

Systematic review of systemic sclerosis-specific instruments for the EULAR Outcome Measures Library: An evolutional database model of validated patient-reported outcomes

The EULAR Outcome Measures Library (OML) is a freely available database of validated patient-reported outcomes (PROs). The aim of this study was to provide a comprehensive review of validated PROs specifically developed for systemic sclerosis (SSc) to feed the EULAR OML. A sensitive search was developed in Medline and Embase to identify all validation studies, cohort studies, reviews, or meta-analyses in which the objective were the development or validation of specific PROs evaluating organ involvement, disease activity or damage in SSc. A reviewer screened title and abstracts, selected the studies, and collected data concerning validation using ad hoc forms based on the COSMIN checklist. From 13,140 articles captured, 74 met the predefined criteria. After excluding two instruments as they were unavailable in English the selected 23 studies provided information on seven SSc-specific PROs on different SSc domains: burden of illness (symptom burden index), functional status (Scleroderma Assessment Questionnaire), functional ability (scleroderma Functional Score), Raynaud's phenomenon (Raynaud's condition score), mouth involvement (Mouth Handicap in SSc), gastro-intestinal involvement (University of California Los Angeles-Scleroderma Clinical Trial Consortium Gastro-Intestinal tract 2.0), and skin involvement (skin self-assessment). Each of them is partially validated and has different psychometric requirements. Seven SSc-specific PROs have a minimum validation and were included in the EULAR OML. Further development in the area of disease-specific PROs in SSc is warranted.

DO DIETARY FISH OIL CONSUMPTION AND PHYSICAL ACTIVITY PARTICIPATION IMPACT THE DURATION, FREQUENCY AND PERCEIVED SEVERITY OF ATTACKS IN PATIENTS WITH RAYNAUD'S PHENOMENON?

INTRODUCTIONRaynaud's phenomenon is a disease characterized by temporary vasoconstriction of the digits due to a number of causes. Although the literature focuses on prescription medications to treat Raynaud's patients, it is important to consider the impact of lifestyle (i.e. diet and physical activity (PA)) on the severity of symptoms, duration of attacks, and quality of life for the Raynaud's sufferer. Specifically, the literature has reported consumption of dietary fish oil (or eicosapentaenoic acid (EPA)) has vasodilatory effects, which may attenaute the painful syptoms that result from the excessive vasoconstriction in the peripheral vascular beds. Additionally, PA is a natural anti‐inflammatory and anti‐oxidant that may protect against the stimulus that causes vasoconstriction. Therefore the purpose of this study is to investigate whether dietary fish oil consumption and PA impact the severity of symptoms, frequency, and duration of attacks in Raynaud's patients.METHODSSurveys were completed by participants recruited from the Raynaud's Associaitons nationwide (n=446, 336 F/130 M). All subjects were included in the study regardless of age, health, medications and location. The group of participants (35.5±11.2 years of age, height: 159.6±14.9 cm, weight: 67.4±17.7 kg) completed a series of validated questionnaires online. The international physical activity questionnaire (IPAQ) was used to determine moderate to vigorous physical activity (MVPA). The Raynaud's condition score was used to assess the severity, duration and percieved diffuclty of symptoms on daily activities. The omega‐3 polyunsaturated fatty acids questionnaire measured dietary consumption of EPA, docosahexaenoic acid (DHA) and α‐linoleic acid, which were summed for total fish oil consumption.RESULTSIn patients with Raynaud's, the total consumption of dietary fish oil did not impact the length of Raynaud's attacks (r= −0.006, p=0.923) or the frequency of the attacks (r=0.072, p=0.233); however patients that indicated they percieved their Raynaud's to be very difficult consumed the highest amounts of fish oil (r=0.196, p=<0.001). In regards to PA, patients that engaged in the greatest amount of MVPA per week percieved their condition to be less dificult (p<0.001), experienced the shortest attacks (p=0.003) and had the lowest number of attacks per week (p<0.001). Patients that reported the highest sitting time per week experienced more attacks per week (r=0.222, p=0.001).CONCLUSIONSThese data suggest that consumption of fish oil is not related to the length or frequency of attacks. However, it appears that achieving higher amounts of PA per week may be effective in attenuating painful symptoms and perceived difficulty of the disease, while increased sitting time is associated with more attacks per week. These findings indicate lifestyle modifications are important to consider when advising patients on management of symptoms associated with Raynaud's phenomenon.Support or Funding InformationKansas State University Office of Undergraduate Research and Creative Inquiry Undergraduate Research Grant

A Randomized Controlled Trial of Acupressure for the Treatment of Raynaud's Phenomenon: The difficulty of conducting a trial in Raynaud's phenomenon.

To examine the effect of acupressure on Raynaud's phenomenon (RP) in a randomized controlled clinical trial (RCT) and to evaluate the difficulties of conducting a RP RCT. A pilot single center RCT of acupressure vs. targeted patient education was conducted for the treatment of RP. Patients with either primary (N = 15) or secondary (N = 8) RP were randomized in an 8-week study. The primary endpoints included a decrease in the frequency and duration of RP. Secondary endpoints included several serum biomarkers including endothelial dysfunction, Raynaud's attack symptoms, Raynaud's Condition Score, and patient and physician global assessments of RP. Primary data analysis was conducted using the last observation carried forward and t-tests or a Wilcoxon rank test was used to compare the two groups. 23 patients were randomized and 7 discontinued prematurely. 78% of patients were female, 96% were Caucasian, and the mean age was 49.8 (SD=16) years. No statistically significant differences were detected between the acupressure vs. education groups in primary and secondary outcomes (p> 0.05). Frequency of attacks decreased by 6.7 attacks (SD=8.8) in the acupressure group vs. 7.2 (SD=12.8) in the education group (p=0.96), and the duration of attacks decreased by 11.4 (SD=19.9) minutes in the acupressure group vs. an increase of 0.8 minutes (SD=11.2) in the education group (p=0.14). There were no adverse events noted in the RCT. This pilot study does not support efficacy of acupressure for RP.

Combination therapy with Bosentan and Sildenafil improves Raynaud's phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis.

The aim of this study was to evaluate in systemic sclerosis (SSc) retrospectively the effect of Bosentan and Sildenafil and their combination on Raynaud's phenomenon (RP), function, and capillaroscopic patterns. One hundred and twenty-three SSc patients (mean age ± sd, 57.69 ± 14.07 years) were retrospectively evaluated and divided into two groups according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification score: group 1 score < 10, group 2 score > 10. Each group was divided into three subgroups according to treatment: Bosentan, Sildenafil, and Bosentan + Sildenafil. Nailfold videocapillaroscopy (NVC), Scleroderma Health Assessment Questionnaire (SHAQ) and Raynaud Condition Score (RCS) were performed at baseline and after 3 and 6 months. In Bosentan (29 patients: 12, group 1; 17, group 2), NVC changed significantly in both groups, after 3 and 6 months (p = 0.00439, group 1; p = 0.00035, group 2). In group 1, the "active" and the "late" patterns reduced, and the "aspecific" increased. In group 2, there was a reduction of late patterns, a worsening of SHAQ (p < 0.005) and an improvement of RCS (p = 0.00014). In Sildenafil (63 patients: 35, group 1; 28, group 2), after 3 months, NVC patterns changed significantly in both groups(p = 0.042 group 1, p = 0.00089 group 2). In group 1, the late and early patterns increased, and the aspecific decreased. In group 2, a significant change of NVC pattern was observed also after 6 months (p = 0.00089): the late pattern increased while the active one reduced. After 6 months, SHAQ was significantly reduced in group 1 (p = 0.00027) and in group 2 (p = 0.0043). RCS improved in both groups (p = 0.0042, group 1; p = 0.0016, group 2). Combination therapy (Bosentan + Sildenafil) (31 patients: 14, group 1; 17, group 2) induced significant changes on NVC only in group 1 after 3 (p = 0.00256) and 6 months (p = 0.000349) with a reduction of the late and active patterns and an increase of the early pattern. In both groups, after 6 months, SHAQ (p < 0.05, group 1; p = 0.00049, group 2) and RCS significantly reduced (group 1, p = 0.00024; group 2, p = 0.0021). Patients treated with Bosentan + Sildenafil show a significant improvement of RCS and NVC. This combination therapy may exert a vascular activity achieving an amelioration of the structure of microvasculature in SSc.

Evaluation of the effect of ambrisentan on digital microvascular flow in patients with systemic sclerosis using laser Doppler perfusion imaging: a 12-week randomized double-blind placebo controlled trial.

IntroductionIn patients with systemic sclerosis (SSc), digital ischemia results from an occlusive microvasculopathy that may not respond adequately to conventional vasodilators. Endothelin receptor antagonists can potentially modify the fibroproliferative vascular remodeling in SSc, and hence their use may be justified in the management of digital ischemia. The objective of this clinical trial was to evaluate the effect of ambrisentan, a selective endothelin type A receptor antagonist, on microvascular blood flow in patients with limited systemic sclerosis (SSc) using laser Doppler perfusion imaging (LDPI).MethodsIn this randomized, double-blind, placebo controlled study we enrolled 20 patients with limited SSc. Fifteen patients received ambrisentan 5 mg daily for one month and then 10 mg daily for two months, and five received a placebo. There were three visits: weeks 0 (baseline), one and 12. Three patient-oriented questionnaires were completed at each visit: Scleroderma-Health Assessment Questionnaire (S-HAQ), Raynaud Condition Score (RCS), and Pain-Visual Analog Scale (P-VAS). At each visit, LDPI was used to obtain three blood flow readings involving regions of interest in second to fifth fingers of the non-dominant hand at room temperature (25°C) and after cooling (10°C) for two minutes.ResultsThere were 16 females (80%); mean age was 50 years. None of the differences in blood flow (as measured by LDPI) were significant both at baseline and after cooling. However, patients in the ambrisentan group showed significant improvement in the patient-oriented outcomes: RCS (P = 0.001) and S-HAQ score (P = 0.005).ConclusionsThis pilot study did not show evidence of significant increase in digital blood flow over time; however, there was an improvement in RCS and S-HAQ score. We conclude that continuous use of ambrisentan for three months does not seem to significantly improve digital blood flow in SSc patients.Trial registrationClinicaltrials.gov NCT01072669. Registered 19 February 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0558-9) contains supplementary material, which is available to authorized users.

AB0643 The Ψ-Reuma Project: Role of Early and Recent Life Events on Systemic Sclerosis (SSC) Clinical Presentation and Course

BackgroundStressful Life Events (SLEs) may play a role in the etiopathogenesis of autoimmune diseases, especially during childhood (early SLEs) and in the year prior to the onset of the disease...

Efficacy of bosentan in the treatment of Raynaud’s phenomenon in patients with systemic sclerosis never treated with prostanoids

The objective of this study was to evaluate the efficacy of the endothelin receptor antagonist, bosentan, in patients with Raynaud's phenomenon secondary to systemic sclerosis never treated with prostanoids and without digital ulcers. The study design is a preliminary, prospective open label trial. The patients recruited took one 62.5 mg dose of bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 24 weeks. Of the 10 patients recruited, all completed the study. The reduction in Raynaud's phenomenon attacks at week 24 from the baseline was statistically significant (Δ-1.3, P=0.0126). The Raynaud's condition score showed a statistically significant improvement (Δ-1.4, P=0.0279), as did the visual analog pain scale (Δ-1.5, P=0.0016) at the 24th week. Bosentan appears to be effective and may be a valid alternative for the treatment of severe secondary Raynaud's phenomenon for patients where prostanoids therapy is contraindicated or refused.

NXCL-4950, a novel composite applicable to peripheral skin, is capable of increasing skin temperature by enhancing capillary circulation

Rapid skin warming and prompt correct medical treatment lead to dramatic improvement in patients with peripheral capillary-related damage, such as injuries, Raynaud disease and frostbite. To characterize a novel composite, NXCL-4950, for use in a cosmetic lotion. The effects of NXCL-4950 on enhancing skin blood flow, skin temperature warming, and expansion of peripheral blood vessels and scalp microvessels were investigated. Monitoring by laser Doppler perfusion imaging and thermal imaging showed that application of NXCL-4950 to the hands increased skin blood flow and temperature relative to the control (or placebo) group. For the 20 participants with a high Raynaud Condition Score, application of NXCL-4950 to the skin resulted in a mean increase of 215.53% in microvessel diameter and mean increase of 164.96% in the speed of blood flow. When NXCL-4950 was applied to the scalp, the microvessels around the hair roots were clearly visible after 20 min. NXCL-4950 is a potential candidate for enhancing peripheral skin temperature, and might be useful in the treatment of capillary-related disorders.

Evaluation of Test Characteristics for Outcome Measures Used in Raynaud's Phenomenon Clinical Trials

Randomized controlled trials (RCTs) in Raynaud's phenomenon (RP) have shown conflicting efficacy data. Also, there is no consensus on the outcome measures that should be used. Our objectives were to assess the reliability of individual core set measures used in 3 RCTs, evaluate the placebo response for individual core set measures, and determine if a composite of individual core set measures will decrease the placebo response, which may improve our ability to see treatment effects in future trials. We analyzed core set measures from 249 patients in the placebo-treated groups from 3 RCTs. Core set measures analyzed included the Raynaud's Condition Score (RCS); patient and physician assessment of RP; pain, numbness, and tingling during an RP attack; average number of attacks/day; and duration of attacks. Intraclass correlation coefficients (ICCs) were calculated during the run-in period to the RCTs. ICCs of ≥0.70 were observed for the RCS, attack symptoms, and average attacks/day. A high placebo response rate was observed for all individual core measures except the duration of attacks. For the RCS, the placebo response ranged from 56% with ≥10% improvement to 19.5% with ≥60% improvement. In contrast, placebo response rates of 10-20% were observed when several core set measures were combined to develop a composite score. Outcome measures used in RCTs of RP are associated with marked variability. A combination of outcome measures is associated with low placebo responses. Future studies are needed to assess if a composite score will be able to differentiate placebo from an effective agent.

Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials

IntroductionRecent controlled trials have assessed the efficacy of phospodiesterase-5 (PDE-5) inhibitors in secondary Raynaud's phenomenon (RP). However, the conclusions are conflicting, and whether these drugs are effective remains unclear. The...

Measures of systemic sclerosis (scleroderma): Health Assessment Questionnaire (HAQ) and Scleroderma HAQ (SHAQ), Physician‐ and Patient‐Rated Global Assessments, Symptom Burden Index (SBI), University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT) 2.0, Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) (Mahler's Index), Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), and Raynaud's Condition Score (RCS)

Measures of systemic sclerosis (scleroderma): Health Assessment Questionnaire (HAQ) and Scleroderma HAQ (SHAQ), Physician‐ and Patient‐Rated Global Assessments, Symptom Burden Index (SBI), University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT) 2.0, Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) (Mahler's Index), Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), and Raynaud's Condition Score (RCS)

Modified-release sildenafil reduces Raynaud's phenomenon attack frequency in limited cutaneous systemic sclerosis

To examine the effect of sildenafil in patients with Raynaud's phenomenon (RP) secondary to limited cutaneous systemic sclerosis (lcSSc). In this double-blind, placebo-controlled study, 57 patients with RP secondary to lcSSc were randomized to receive modified-release sildenafil 100 mg once daily for 3 days followed by modified-release sildenafil 200 mg once daily for 25 days or placebo. The primary assessment was the percentage change in the number of RP attacks per week in the per-protocol population. Secondary end points included Raynaud's Condition Score, duration of attacks, RP pain score, endothelial dysfunction assessed by a peripheral arterial tonometric (PAT) device, and serum biomarker levels. The mean percentage reduction from baseline to day 28 in attacks per week was greater for modified-release sildenafil than for placebo (-44.0% versus -18.1%, P = 0.034); the mean number of attacks per week improved from 25.0 at baseline to 19.3 after placebo treatment and from 30.5 to 18.7 after modified-release sildenafil treatment (P = 0.244). Decreases from baseline in Raynaud's Condition Score, duration of attacks, and RP pain score were not significantly different between groups. Mean values and changes from baseline in PAT responses and serum biomarker levels were similar between groups. The most frequent adverse events were headache and dyspepsia; the majority of adverse events were mild or moderate. Our findings indicate that modified-release sildenafil reduced attack frequency in patients with RP secondary to lcSSc and was well tolerated. Modified-release sildenafil may be a treatment option in this patient population.

Bosentan Improves Skin Perfusion of Hands in Patients with Systemic Sclerosis with Pulmonary Arterial Hypertension

Our aim was to investigate effects of bosentan on hand perfusion in patients with systemic sclerosis (SSc) with pulmonary arterial hypertension (PAH), using laser Doppler perfusion imaging (LDPI). We enrolled 30 SSc patients with PAH, 30 SSc patients without PAH, and 30 healthy controls. In SSc patients and healthy controls at baseline, skin blood flow of the dorsum of the hands was determined with a Lisca laser Doppler perfusion imager. The dorsal surface of the hands was divided into 3 regions of interest (ROI). ROI 1 included 3 fingers of the hand from the second to the fourth distally to the proximal interphalangeal finger joint. ROI 2 included the area between the proximal interphalangeal and the metacarpophalangeal joint. ROI 3 included only the dorsal surface of the hand without the fingers. LDPI was repeated in SSc patients and controls after 4, 8, and 16 weeks of treatment. In SSc patients, nailfold videocapillaroscopy and Raynaud Condition Score (RCS) were performed at baseline and at 4, 8, and 16 weeks. SSc patients with PAH enrolled in the study received treatment with bosentan as standard care for PAH. In these patients with PAH, after 8 and 16 weeks of treatment, bosentan improved minimum, mean, and maximum perfusion and the perfusion proximal-distal gradient. Bosentan seems to be most effective in patients with the early and active capillaroscopic pattern than in patients with the late pattern. Bosentan improved skin blood flow principally in the ROI 1 compared to the ROI 2 and ROI 3. Bosentan restored the perfusion proximal-distal gradient in 57% of SSc patients with the early capillaroscopic pattern. No significant differences from baseline were observed in the RCS in SSc patients with PAH. Bosentan improved skin perfusion in SSc patients with PAH, although it did not ameliorate symptoms of Raynaud's phenomenon. Skin blood perfusion increased in SSc patients with PAH, particularly in the skin region distal to the proximal interphalangeal joint, and in patients with the early/active capillaroscopic pattern. Double-blind randomized clinical trials are needed to evaluate the effects of bosentan on skin perfusion of SSc patients without PAH and with active digital ulcers.

Randomized Placebo-Controlled Crossover Trial of Tadalafil in Raynaud’s Phenomenon Secondary to Systemic Sclerosis

Raynaud's phenomenon (RP) is an important clinical feature of systemic sclerosis (SSc) for which consistently effective therapies are lacking. The study was designed to assess the safety, tolerability, and efficacy of tadalafil, a selective, long acting type V cyclic GMP phosphodiesterase (PDE-5) inhibitor, in this clinical syndrome. We performed a prospective, randomized, double-blind, placebo-controlled, crossover study comparing oral tadalafil at a fixed dose of 20 mg daily for a period of 4 weeks versus placebo in women with RP secondary to SSc. Thirty-nine subjects completed the study and were evaluable. There were no statistically significant differences in Raynaud Condition Score (RCS), frequency of RP episodes, or duration of RP episodes between treatment groups. Placebo response was a confounding factor. Tadalafil was well tolerated. Tadalafil appears to be safe and well tolerated but lacks efficacy in comparison to placebo as a treatment for RP secondary to SSc.

Long-term beneficial effects of statins on vascular manifestations in patients with systemic sclerosis

We conducted a 24-month, open-label trial to evaluate the long-term effects of statins on vascular symptoms in patients with systemic sclerosis (SSc). Ten patients received 10 mg/day atorvastatin, but two dropped out to treat other organ involvement. Raynaud's phenomenon, global measures of health, and psychological scales were assessed in addition to circulating angiogenic factors and endothelial activation/injury markers in eight patients at 0 (pretreatment), 1, 3, 12, and 24 months of treatment. Circulating endothelial progenitor cells (EPCs) were serially quantified by cell sorting and three-color flow cytometry. There were no adverse events. Raynaud's phenomenon improved during atorvastatin treatment, with significant reductions in the Raynaud's Condition Score (P = 0.01) and the patient assessment by visual analog scale (P = 0.0003). SSc-associated upregulation of angiogenic factors and vascular endothelial activation/injury markers were reduced (P < 0.01 for all comparisons). Improvement in these parameters was best at 12 and 24 months of treatment. The EPC number was increased at 1 month of treatment (P < 0.01), but soon dropped below baseline. This pilot study suggests that statins may be beneficial in treating vascular manifestations of SSc, through their pleiotropic effects. However, this treatment did not correct the defect in EPC recruitment.

The minimally important difference and patient acceptable symptom state for the Raynaud's condition score in patients with Raynaud's phenomenon in a large randomised controlled clinical trial

BackgroundThe Raynaud's condition score (RCS) is a validated outcome measure for Raynaud's phenomenon (RP).ObjectiveTo assess the minimally important difference (MID) and patient acceptable symptom state (PASS) for RCS in patients...

MQX‐503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: A randomized, controlled trial

Raynaud's phenomenon (RP) affects 3-9% of the general population and >90% of patients with systemic sclerosis. Nitrates are often prescribed for the treatment of RP, but currently available formulations are limited by side effects, particularly headaches, dizziness, and skin irritation. The purpose of this study was to evaluate the tolerability and efficacy of a novel formulation of topical nitroglycerin, MQX-503, in the treatment of RP in an ambulatory setting. We conducted a multicenter, randomized, placebo-controlled study with a 2-week single-blind run-in period to determine baseline severity, followed by a 4-week double-blind treatment phase. Two hundred nineteen adult patients with a clinical diagnosis of primary or secondary RP received 0.9% MQX-503 gel or matching placebo during the treatment period. Gel was applied immediately before or within 5 minutes of the beginning of an episode of RP (maximum of 4 applications daily). End points included the change in the mean Raynaud's Condition Score (RCS; scale 0-10), the frequency and duration of episodes, and subjective assessments at the target week (the week during the treatment phase that most closely matched the run-in period in terms of ambient temperature) compared with baseline. The mean (%) change in the RCS at the target week compared with baseline was significantly greater in the MQX-503 group (0.48 [14.3%]) than that in the placebo group (0.04 [1.3%]; P = 0.04). Changes in the frequency and duration of RP episodes and subjective assessments were not statistically different between the groups. MQX-503 had a side effect profile similar to that of placebo. MQX-503 is well tolerated and more effective than placebo for the treatment of RP.