ABSTRACT
BACKGROUND: Hyperimmune caprine serum (HICS) is a novel biological therapy with potential benefit for skin in established diffuse cutaneous systemic sclerosis. Here we report multiplex protein analysis of blood samples from a placebo-controlled phase II clinical trial and explore mechanisms of action and markers of response. METHODS: Patients were treated with HICS (n = 10) or placebo (n = 10) over 26 weeks, with follow-up open-label treatment to 52 weeks in 14 patients. Serum or plasma samples at baseline, 26 and 52 weeks were analysed using multiplex or individual immunoassays for 41 proteins. Patterns of change were analysed by clustering using Netwalker 1.0, Pearson coefficient and significance analysis of microarrays (SAM) correction. RESULTS: Cluster analysis, SAM multiplex testing and paired comparison of individual analytes identified proteins that were upregulated or downregulated during treatment with HICS. There was upregulation of the hypothalamo-pituitary-adrenal axis after HICS treatment evidenced by increases in α-MSH and ACTH in cases treated with HICS. Interestingly, significant increase in PIIINP was associated with HICS treatment and improved MRSS suggesting that this may be a marker of extracellular matrix turnover. Other relevant factors reduced in HICS-treated patients compared with controls, although not reaching statistical significance included COMP, CCL2, IL6, TIMP2, Fractalkine and TGFß1 levels. CONCLUSIONS: Our results suggest mechanisms of action for HICS, including upregulation of α-MSH, that has been shown to be anti-fibrotic in preclinical models, and possible markers to be included in future trials targeting skin in diffuse cutaneous systemic sclerosis. TRIAL REGISTRATION: Eudract, No. 2007-003122-24. ClinTrials.gov, No. NCT00769028 . Registered 7 October 2008.
Subject(s)
Biomarkers/blood , Blood Proteins/therapeutic use , Immunologic Factors/therapeutic use , Scleroderma, Diffuse/blood , Scleroderma, Diffuse/drug therapy , Adult , Aged , Animals , Female , Goats , Humans , Male , Middle Aged , Multiplex Polymerase Chain Reaction , SkinABSTRACT
We reviewed the results and side-effect profile of the Dysport preparation of botulinum toxin A (BTA) in the management of the adductor spasmodic dysphonia. We performed 272 injection episodes in 68 patients, 42 (62%) female, 26 (38%) male. A total of 116 of these injections were unilateral, and 156 were bilateral; 94% of the injections were considered to have been successful with a voice score of 2 or higher. The mean duration of effect (injection intervals) was 128.8 days in the unilateral cohort and 118.7 days in the bilateral (P > 0.05). We injected a relatively lower dose of BTA for unilateral injection episodes in our institution compared to those reported by others to produce comparable results and side-effect profiles.
Subject(s)
Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/therapeutic use , Dysphonia/drug therapy , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/therapeutic use , Botulinum Toxins, Type A/adverse effects , Cohort Studies , Female , Functional Laterality , Humans , Injections/methods , Male , Middle Aged , Neuromuscular Agents/adverse effects , Retrospective Studies , Severity of Illness Index , Time Factors , Treatment Outcome , Voice/drug effectsABSTRACT
OBJECTIVES: In this preliminary prospective study, we compared unilateral and bilateral thyroarytenoid muscle injections of Botulinum toxin (Dysport) in 31 patients with adductor spasmodic dysphonia, who had undergone more than 5 consecutive Dysport injections (either unilateral or bilateral) and had completed 5 concomitant self-rated efficacy and complication scores questionnaires related to the previous injections. We also developed a Neurophysiological Scoring (NPS) system which has utility in the treatment administration. METHOD AND MATERIALS: Data were gathered prospectively on voice improvement (self-rated 6 point scale), length of response and duration of complications (breathiness, cough, dysphagia and total voice loss). Injections were performed under electromyography (EMG) guidance. NPS scale was used to describe the EMG response. Dose and unilateral/bilateral injections were determined by clinical judgment based on previous response. Time intervals between injections were patient driven. RESULTS: Low dose unilateral Dysport injection was associated with no significant difference in the patient's outcome in terms of duration of action, voice score (VS) and complication rate when compared to bilateral injections. Unilateral injections were not associated with any post treatment total voice loss unlike the bilateral injections. CONCLUSION: Unilateral low dose Dysport injections are recommended in the treatment of adductor spasmodic dysphonia.
