Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan

<p>Abstract</p> <p>Background</p> <p>This study assessed the effectiveness and safety of bosentan when administered to thromboangiitis obliterans (Buerger's disease) patients.</p> <p>Methods</p> <p>A clinical pilot study was designed in which patients with ulcer and/or pain at rest were treated with bosentan p.o. at a dose of 62.5 mg twice daily during the first month, which was thereafter up-titrated to 125 mg twice daily. The study endpoints were clinical improvement rate, major or minor amputation rate, haemodynamic changes, changes in endothelial function and angiographic changes.</p> <p>Results</p> <p>Seven out of 12 patients were male (58%). Median age was 39 years (range 29-49). The median follow-up was 20 months (range 11-40). All patients were smokers. With bosentan treatment, new ischaemic lesions were observed in only one patient. Overall, clinical improvement was observed in 12 of the 13 extremities (92%). Only two out of 13 extremities underwent amputation (one major and one minor) after bosentan treatment. After being assessed by digital arteriography with subtraction or angio-magnetic resonance imaging, an increase of distal flow was observed in 10 out of the 12 patients. All patients experienced a statistically significant improvement in their BAFMD values (mean: 1.8 at baseline; 6.6 at the end of the treatment; 12.7 three months after the end of the treatment; p < 0.01).</p> <p>Conclusion</p> <p>Bosentan treatment may result in an improvement of clinical, angiographic and endothelial function outcomes. Bosentan should be investigated further in the management of TAO patients. Larger studies are required to confirm these results.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01447550">NCT01447550</a></p

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Systematic review of randomized controlled trials in the treatment of dry eye disease in Sjogren syndrome

Primary Sjögren’s syndrome is an autoimmune disease characterized by dry eye and dry mouth. We systematically reviewed all the randomized controlled clinical trials published in the last 15 years that included ocular outcomes. We found 22 trials involving 9 topical, 10 oral, 2 intravenous and 1 subcutaneous modalities of treatment. Fluoromethalone eye drops over 8 weeks were more effective than topical cyclosporine in the treatment of dry eye symptoms and signs; similarly, indomethacin eye drops over 1 month were more efficacious than diclofenac eye drops. Oral pilocarpine 5 mg twice daily over 3 months was superior to use of lubricants or punctal plugs for treating dry eye, but 5% of participants had gastrointestinal adverse effects from pilocarpine, though none discontinued treatment. In contrast, etanercept, a TNF-alpha blocking antibody, administered as subcutaneous injections twice weekly, did not improve dry eye significantly compared to placebo injections. In conclusion, topical corticosteroids have been shown to be effective in dry eye associated with Sjögren’s syndrome. As some topical non-steroidal anti-inflammatory drugs may be more effective than others, these should be further evaluated. Systemic secretagogues like pilocarpine have a role in Sjögren’s syndrome but the adverse effects may limit their clinical use. It is disappointing that systemic cytokine therapy did not produce encouraging ocular outcomes but participants should have assessment of cytokine levels in such trials, as those with higher baseline cytokine levels may respond better.published_or_final_versio

Safety and efficacy of recombinant γ interferon in the of treatment of systemic sclerosis

Objective - To evaluate the safety and efficacy of recombinant γ interferon (rIFNγ) in the treatment of patients with systemic sclerosis. Methods - Sixteen patients with systemic sclerosis were treated with r-IFNγ, 60 μg m-2 low dose, n = 10) and 150 μg m-2 (high dose, n = 6), three times weekly in an open phase I/II trial of eight months duration. The patients were stratified in low and high dose according to the severity and the extent of scleroderma; the two groups were comparable. Results - The treatment was well tolerated. The most common side effects, almost certainly related to r-IFNγ, were fever, chills, dizziness, headache, and severe flu-like syndrome with decreasing intensity with the time of treatment. Severe aphthous stomatitis (n = 1), ventricular tachycardia (n = 1), severe oesophageal ulcers due to gastro-oesophageal reflux (n = 1), disease exacerbation alone with frank arthritis and slight pericardial effusion (n = 1), and inability to conform to the requirements of the study (n = 1) were the reasons for discontinuing treatment. Side effects and degree of response were evident during the first five months of treatment. A significant decrease in mean skin thickness score was observed and was higher in the high dose group. Reactive oxygen species of peripheral neutrophils and soluble interleukin-α receptor serum concentrations were higher than those of normal individuals at study entry and decreased in parallel with clinical improvement. Conclusions - Treatment of systemic sclerosis patients with r-IFNγ was relatively safe and well tolerated for doses as high as 150 μg m-2 three times weekly. Side effects and the degree of response can be seen during the first months of therapy and can be used as predictors of ultimate toxicity or response. The drug seems to be effective in treating cutaneous scleroderma

Oral pilocarpine for the treatment of ocular symptoms in patients with Sjögren's syndrome: a randomised 12 week controlled study

Objective: To evaluate the efficacy and side effects of oral pilocarpine for the treatment of ocular symptoms in patients with primary Sjögren's syndrome (SS). Methods: A 12 week, single centre, randomised controlled study was performed. Twenty nine patients were randomly assigned to receive oral pilocarpine (5 mg twice a day), 28 only artificial tears, and 28 inferior puncta occlusion. Patients receiving oral pilocarpine and those with inferior puncta occlusion also received artificial tears. Patients were evaluated at baseline and throughout the study for their subjective global assessment of dry eyes and for their objective assessment of dry eyes (Schirmer's-I test, rose bengal test, and imprint test). Results: Patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes, as was evaluated by improvement of >55 mm on a visual analogue scale (VAS) for responses to the eye questionnaire, compared with patients treated with artificial tears (p<0.001) and those with inferior puncta occlusion (p<0.05). Furthermore, patients receiving oral pilocarpine also showed greater objective improvement, as measured by the rose bengal test (p<0.05), while Schirmer's-I test showed no differences between the treated groups. Commonly reported adverse events were headache, increased sweating, nausea, and vomiting in the pilocarpine group, while one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study. Conclusion: 10 mg of pilocarpine daily given to patients with SS for 12 weeks had a beneficial effect on subjective eye symptoms, as evaluated by improvement >55 mm on a VAS. Additionally, an improvement of rose bengal staining was noted, but an increase in tear production, as measured by the Schirmer-I test, was not substantiated