Cream versus ointment: Randomized single-blinded study on the adherence to treatment with topical methylprednisolone aceponate.

BACKGROUND: Overall adherence in the treatment of chronic dermatoses is poor. Textbooks state an adherence dependence on galenics. TRIAL DESIGN: Prospective, randomized, parallel-grouped, single-blinded (investigator), monocentric clinical trial (phase IV) on the adherence to treatment of chronic mild to moderate hand eczema with topical methylprednisolone aceponate (MPA, Advantan®) in different vehicles. OBJECTIVES AND ENDPOINTS: Primary objective was the assessment of the adherence depending on vehicle type in patients with chronic hand eczema. Secondary objective was improvement after a 4-week treatment period. Primary Endpoint Adherence is defined as the percentage of patients applying at least aimed daily dose. Prescribed daily dose was defined as the planned number of applications per day (1) * surface (measured) * aimed amount per application (mg/cm2 ). Truly applicated daily dose was evaluated as individual mean amount per dose * individual mean number of applications per day. Adherence was assumed, if truly applicated daily dose is at least 75% of the prescribed daily dose and the individual mean number of applications per day is at least 0.85. Secondary Endpoint Efficacy was measured by improvement of Hand Eczema Severity Index (HECSI) and Investigator's Global Assessment (IGA) after a 4-week treatment period and in addition to Quality of Life in Hand Eczema Questionnaire (QOLHEQ) and Visual Analogue Scale (VAS) to assess pruritus. METHODS: Number of participants randomized to each group 40, 80 total. Group 1 MPA-C: Methylprednisolone aceponate 0.1% cream and barrier repair emollient (Bepanthen® Sensiderm). Group 2 MPA-FO: Methylprednisolone aceponate 0.1% fatty ointment and barrier repair emollient (Bepanthen® Sensiderm). Adherence to treatment was compared via Fisher's exact test. RESULTS: Of the patients, 48% were adherent according to our definition. There was no significant difference between MPA-C (42.1%) and MPA-FO (54.1%; p = 0.36; group difference-12.0%, 95% CI-34.3%-11.5%). Generalized-linear-model-analysis of adherence to study treatment with factors emollient use, treatment, time and treatment-time interaction showed a parallel between adherence and amount of emollient use (odds ratio 1.74, p = 0.0038; 95% CI-1.22-2.52). Improvement of hand eczema was seen according to clinical scores without remarkable differences between the groups. CONCLUSIONS: No dependence of adherence on galenics of topical treatment of chronic hand eczema could be proved. Patients who use more emollient tend to be more adherent to the topical treatment.

Sinonasal inhalation of dornase alfa administered by vibrating aerosol to cystic fibrosis patients: a double-blind placebo-controlled cross-over trial.

BACKGROUND: Chronic rhinosinusitis significantly impairs CF patients' quality of life and overall health. The Pari-Sinus™ device delivers vibrating aerosol effectively to paranasal sinuses. After a small pilot study to assess sinonasal inhalation of dornase alfa and placebo (isotonic saline) on potential sinonasal outcome measures, we present the subsequent prospective double-blind placebo-controlled crossover-trial. METHODS: 23 CF patients were randomised to inhale either dornase alfa or isotonic saline for 28 days with the Pari-Sinus™ and after 28 days (wash-out) crossed over to the alternative treatment. The primary outcome parameter was primary nasal symptom score in the disease-specific quality of life Sino-Nasal Outcome-Test-20 (SNOT-20: nasal obstruction/sneezing/runny nose/thick nasal discharge/reduced smelling). RESULTS: Primary nasal symptoms improved significantly with dornase alfa compared with no treatment, while small improvements with isotonic saline did not reach significance. SNOT-20 overall scores improved significantly after dornase alfa compared with isotonic saline (p=0.017). Additionally, sinonasal dornase alfa but not isotonic saline significantly improved pulmonary function (FEF75-25: p=0.021). CONCLUSION: Vibrating sinonasal inhalation of dornase alfa reduces rhinosinusitis symptoms in CF.

Sinonasal inhalation of dornase alfa in CF: A double-blind placebo-controlled cross-over pilot trial.

OBJECTIVE: The paranasal sinuses are almost always involved in cystic fibrosis, and chronic rhinosinusitis and nasal polyps are very frequent in the disease. Hereby, the patients' quality of life and their overall health are relevantly impaired. Although dornase alfa, a mucolytic agent, may also be effective in the upper airways, deposition of inhaled drugs into paranasal sinuses is substantially limited. The novel PARI SINUS™ nebuliser has been shown in deposition studies to deliver aerosol into paranasal sinuses but has not yet been clinically tested. This DBPC pilot-trial applying dornase alfa aims to evaluate outcome parameters and sample sizes for a subsequent efficacy trial. METHODS: Primary outcome parameters assessed were the Sino-Nasal Outcome Test (SNOT-20, a disease-specific quality of life assessment tool) and ventilated volume as measured by magnetic resonance imaging. Five CF patients were randomised to inhale either dornase alfa or 0.9% NaCl for 28 days and, after a wash-out period of 28 days, crossed over to the alternative treatment. RESULTS: Whereas normal saline was not associated with relevant changes in SNOT-20 scores, dornase alfa improved quality of life (p=0.043). MRI results showed no definite trend. CONCLUSION: This first clinical study with the novel device gives promising results for the new therapeutic concept of sinonasal inhalation with vibrating aerosols in regard to further analysis involving larger collectives.