Supplementary Online Content

Transcription

1 Supplementary Online Content Caglayan E, Axmann S, Hellmich M, Moinzadeh P, Rosenkranz S. Vardenafil for the treatment of Raynaud phenomenon: a randomized, double-blind, placebocontrolled crossover study. Arch Intern Med. Published online June 18, doi: /archinternmed eappendix. Supplemental methods etable. Baseline demographics efigure 1. CONSORT flow diagram efigure 2. Trend of the Raynaud condition score (RCS) during the course of the study This supplementary material has been provided by the authors to give readers additional information about their work.

2 eappendix. Supplemental Methods Inclusion criteria to the study consisted of a definite diagnosis of RP, which included the presence of typical clinical symptoms, impaired digital blood flow, and history of RPrelated attacks for at least 1 year, an age between 18 and 80 years and written informed consent. Exclusion criteria can be reviewed in detail online ( Briefly, patients with severe cardiac, renal, hepatic or bleeding disorders were excluded from this trial. In addition, patients with active digital ulcers were also excluded. RP was diagnosed if patients had a history of sensitivity to the cold and have episodic pallor or cyanosis of the distal portions of the digits (or both) after exposure to the cold 1. Nailfold capillary microscopy was performed in all patients at the initial visit in order to confirm or exclude secondary RP due to CTD 2. Abnormal nailfold videocapillaroscopy scleroderma patterns were present in SSc patients, which were subdivided into early (combination of ectatic capillaries, microhaemorrhages, well preserved capillary density/distribution, with no loss of capillaries), active (combination of frequent giant capillaries, micrphaenorrhages, moderate loss of capillaries) and late (few or no giant capillaries left, severe loss of capillaries combined with bushy capillaries) NVC scleroderma pattern 3. Diagnosis and classification of SSc was performed using clinical, capillaroscopic and serologic criteria, as previously described 4.

3 The RCS was recorded by a standardized patient questionnaire which includes the number and daily duration of RD related attacks, as previously described 5. Patients were asked to rate their RD related impairment on a scale ranging from 0 (none) to 10 (very severe) on each day throughout the study. Peripheral blood flow in the index finger was measured by the use of a laser Doppler perfusion imager (Lisca PIM 1.0; Lisca development, Linkoping, Sweden) after adjustment to room temperature (22 C) at time point 0 (baseline), 1 hour after the initial drug intake, and after 6 weeks of treatment. Study medication was prepared by the hospital pharmacy according to computergenerated, sex stratified, pseudo random sequences (permuted blocks of lengths 4 and 6). References 1. Wigley FM. Clinical practice. Raynaud's Phenomenon. N Engl J Med. Sep ;347(13): Caglayan E, Huntgeburth M, Karasch T, et al. Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud disease. Arch Intern Med. Jan ;166(2): Smith V, Decuman S, Sulli A, et al. Do worsening scleroderma capillaroscopic patterns predict future severe organ involvement? a pilot study. Ann Rheum Dis. Mar 8.

4 4. Genth E, Krieg T. [Systemic sclerosis diagnosis and classification]. Z Rheumatol. Jul 2006;65(4): Black CM, Halkier Sorensen L, Belch JJ, et al. Oral iloprost in Raynaud's phenomenon secondary to systemic sclerosis: a multicentre, placebo controlled, dose comparison study. Br J Rheumatol. Sep 1998;37(9):

5 etable. Baseline demographics. BMI, Body mass index; CCB, Calcium channel blockers; ERA, Endothelin receptor antagonist; MCTD, mixed connective tissue disease; SLE, Systemic lupus erythematosus. *All vasoactive drugs were discontinued at least one week prior to study entry. Baseline demographics Mean±SD Range Age (years) 51.7± BMI (kg/m 2 ) 24.0± n % Sex female male Type of RD primary secondary Underlying disease for 2 RP lcssc dcssc Overlap syndrome Undifferentiated CTD Smoker no yes RP treatment prior to study* CCB ERA i.v. prostaglandin Nitroglycerin PDE5 Inhibitor Pentoxyfilline 1 1.9

6 efigure 1. CONSORT Flow Diagram (Abbr.: ITT intention to treat, (S)AE (serious) adverse event )

7 efigure 2. Trend of the Raynaud condition score (RCS) during the course of the study. The Hills-Armitage approach to the 2 2 cross-over design yields p=0.032 (Vardenafil vs. Placebo, Wilcoxon rank sum test). Error bars denote standard error of mean (SEM).