Calcipotriol plus betamethasone dipropionate aerosol foam provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomized, controlled PSO-ABLE study.

BACKGROUND: Fixed combination calcipotriol 50 µg/g (Cal) plus betamethasone 0.5 mg/g (BD) foam has been developed as a new treatment option for patients with psoriasis. METHODS: The randomized, parallel-group, investigator-blinded Phase III, 12-week PSO-ABLE study compared the efficacy and safety of Cal/BD foam with Cal/BD gel. Patients aged ≥18 years with mild-to-severe psoriasis were randomized 4:4:1:1 to once-daily Cal/BD foam, Cal/BD gel, foam vehicle or gel vehicle (NCT02132936). The primary efficacy endpoint was the proportion of patients who were clear/almost clear with a ≥ 2 grade improvement according to the physician's global assessment of disease severity (i.e. treatment success) at week 4 for Cal/BD foam vs. week 8 for Cal/BD gel. Secondary efficacy endpoints included: proportion of patients achieving at least a 75% reduction in modified psoriasis area and severity index (mPASI75), and time to treatment success (TTTS). Safety was monitored throughout. RESULTS: A total of 463 patients were randomized: Cal/BD foam (n = 185), Cal/BD gel (n = 188), foam vehicle (n = 47), gel vehicle (n = 43); overall completion rate was 90%. Cal/BD foam achieved higher treatment success rates (38% vs. 22%; P < 0.001) and mPASI75 (52% vs. 35%; P < 0.001) by week 4 than Cal/BD gel by week 8. Median TTTS with Cal/BD foam was 6 weeks; this could not be determined for Cal/BD gel as 50% treatment success was not achieved (P < 0.001). Adverse drug reactions were reported in 14 (7.6%) Cal/BD aerosol foam patients and 7 (3.7%) Cal/BD gel patients; all were single events except for itch with Cal/BD aerosol foam (n = 5; 2.7%) and worsening psoriasis with Cal/BD gel (n = 3; 1.6%). CONCLUSION: Cal/BD aerosol foam showed significantly greater efficacy after 4 weeks, than 8 weeks of treatment with Cal/BD gel, with similar tolerability.

Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis.

BACKGROUND: Heparin has anti-inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis. AIM: To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis. STUDY DESIGN: A prospective, double-blind, randomized, placebo-controlled, multi-centre trial comparing tinzaparin 175 anti-Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti-Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment. RESULTS: One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty-eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin-placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo. CONCLUSION: This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.

A new calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris.

BACKGROUND: Topical corticosteroids and calcipotriol have been used separately for many years to treat psoriasis. A new combination ointment has been formulated, which contains both calcipotriol and the corticosteroid betamethasone dipropionate. OBJECTIVE: To compare the combination ointment with betamethasone dipropionate ointment, calcipotriol ointment and ointment vehicle in patients with psoriasis vulgaris. METHODS: 1,603 patients were randomised to one of the 4 double-blind treatments used once daily for 4 weeks. RESULTS: The mean percentage change in the PASI at the end of treatment was -71.3 (combination), -57.2 (betamethasone), -46.1 (calcipotriol) and -22.7 (vehicle). The mean difference of combination minus betamethasone was -14.2 (95% CI: -17.6 to -10.8, p < 0.001), of combination minus calcipotriol -25.3 (95% CI: -28.7 to -21.9, p < 0.001) and of combination minus vehicle -48.3 (95% CI: -53.2 to -43.4, p < 0.001). 6.0% of patients (combination) reported local adverse reactions compared to 4.9% (betamethasone), 11.4% (calcipotriol) and 13.6% (vehicle). CONCLUSION: Calcipotriol/betamethasone dipropionate combination ointment used once daily is well tolerated and more effective than either active constituent used alone.

Calcipotriol cream combined with twice weekly broad-band UVB phototherapy: a safe, effective and UVB-sparing antipsoriatric combination treatment. The Canadian Calcipotriol and UVB Study Group.

BACKGROUND: Calcipotriol has been combined with a number of systemic antipsoriatric treatments, improving efficacy or reducing the systemic treatment required. Although studies on calcipotriol and UVB have also been performed, there are no data on the UVB-saving effect of calcipotriol combined with broad-band UVB to reduce overall UVB exposure, while maintaining efficacy. OBJECTIVES: To assess the efficacy and safety of calcipotriol cream (50 microg/g) combined with twice weekly broad-band UVB and to determine if this treatment would require fewer UVB treatments and lower cumulative UVB irradiance when compared to a standard 3 times weekly broad-band UVB regime in patients with extensive psoriasis. METHODS: This multicentre, prospective, randomised, parallel-group, vehicle-controlled, single-blind (investigator) study consisted of a 1-week wash-out phase, 12-week treatment phase and 12-week follow-up phase. Broad-band UVB equipment was standardised and calibrated prior to the study. The UVB starting dose was based on the patient's minimal erythema dose. Assessments included PASI, extent, severity and investigator and patient's overall assessments of the psoriasis. RESULTS: Fewer exposures (12 vs. 19) and less cumulative UVB irradiance (1,570 vs. 5,430 mJ/cm(2)) were required by the calcipotriol + twice weekly UVB group to achieve 80% reduction in PASI (p < 0.001). Similarly, fewer exposures (22 vs. 25) and less cumulative UVB irradiance (4,147 vs. 9,670 mJ/cm(2)) were required by this group to achieve total clearance (p < 0.001). There was no difference in the PASI, patient's and investigator's overall assessments and number of adverse events recorded by either group for both the treatment and follow-up phases. CONCLUSION: Calcipotriol cream + twice weekly broad-band UVB phototherapy is an effective and safe antipsoriatric treatment, resulting in fewer UVB exposures, lower cumulative irradiance and a saving of time.

Flour dust exposure variability in flour mills and bakeries.

As part of a longitudinal study to explore the exposure-response relationship between flour dust exposure and work-related symptoms and skin sensitivity the authors formed exposure groups and estimated various components of variability. This paper describes the between-exposure group, the between-worker and the within-worker variation of personal flour dust exposure in bakeries, flour mills and packing stations. In total 346 samples were collected in 13 exposure groups. The geometric means of the exposure groups ranged from 0.3 up to 9.0 mg m-3. Between-worker variances within exposure groupings were less than the overall between-worker component although substantial differences in exposure between workers remained in some exposure groups. Overall the largest variance component was the between-exposure group component followed by the considerably smaller between-worker and within-worker components.

Correlation between different measures of exposure in a cohort of bakery workers and flour millers.

This paper describes the relationship between continuous and 'grouped' variables for several measures of exposure in a longitudinal study of bakery workers and flour millers. Average shift and peak levels, both for dust and for flour aeroallergen were measured, duration of exposure obtained from questionnaire and cumulative exposure both for dust and for flour aeroallergen calculated. Neither for dust nor for flour aeroallergen was there a correlation between duration of exposure and intensity measures of exposure (peak and average). Moderate to good correlation existed between the various intensity measures of exposures both for dust and for flour aeroallergen. Good correlations existed between measures of exposure of dust and measures of exposure for flour aeroallergen. The degree of correlation was reflected by the fact that the number of workers changing categories depended on which measure of exposure was considered. The higher the correlation coefficient between various measures of exposure the fewer workers changed category. This information provides important information for a better understanding of the exposure-response relationship amongst bakery workers and flour millers.

Peak exposure concentrations of dust and flour aeroallergen in flour mills and bakeries.

As part of an epidemiological study amongst workers exposed to flour we measured peak exposure levels to total dust and flour aeroallergen with personal samplers in bakeries, flour mills and packing stations. Short-term tasks which were expected to give rise to high concentrations of exposure (peaks) were identified. The frequency and duration of these tasks were estimated and their levels of exposure to dust and flour aeroallergen measured. In total 209 samples were taken. The highest exposure concentrations both for dust (geometric mean > 30 mg m-3) and for flour aeroallergen (geometric mean > 500 micrograms m-3) were measured during certain operations. Exposure concentrations for the tasks were often much higher than the levels we had measured over a shift in a previous study. This might be important for sensitization and for the development of asthma. Peak exposure concentrations could be used to explore the exposure-response relationship more comprehensively. In general average flour aeroallergen concentrations increased linearly with average dust concentrations, although there were some exceptions.

Acute infective exacerbations of chronic bronchitis.

Patients with an acute infective exacerbation of chronic bronchitis (AECB) (n = 471) were enrolled into a computer-based general-practice study to determine whether features of past history, presenting symptoms, or findings on examination were predictive of failure to recover. The median age was 68, 56.3% were male, and 82% were current or ex-smokers. All had daily sputum production and 57.5% had moderate or severe airflow obstruction. During the AECB 11.5% were pyrexial, and 80.7% had abnormal auscultatory findings; about half had moderate to severe increases in dyspnoea and airflow obstruction, and the majority had increases in sputum volume and/or purulence. The median number of AECBs in the previous year was three, and one-third of patients had cardiopulmonary disease. The only factors significantly (p < 0.05) predicting failure to recover from an AECB were historical. Neither clinical features at presentation nor antibiotic treatment affected recovery. Coexistent cardiopulmonary disease was a risk factor for returning with a chest problem and for being referred to hospital. The number of chest infections in the previous 12 months was a risk factor for returning with a chest problem. The higher the number of chest infections, the higher the odds of returning with a chest problem. The best combination predicting return with a chest problem was history of cardiopulmonary disease and more than four previous AECBs in the last 12 months. The sensitivity was 75% and specificity 47%.

Measurement of airborne rat urinary allergen in an epidemiological study.

The suitability of radioallergosorbent test (RAST) inhibition to quantify occupational exposure to rat urinary aeroallergen (RUA) has been assessed. When using a constant pool of rat allergic sera, the reproducibility of the assay over 1 year was comparable to that reported for other immunoassays; at 50% RAST inhibition the inter-assay coefficient of variation (CV) was 7.0% and the intra-assay CV was 3.0%. The assay was highly specific for rat urine; mouse urine was 1100-fold less potent at inhibiting the rat urine RAST system. Significant inter-assay variation in the 'high' control was not due to batch variation and was relatively small when compared with the variation in RUA concentrations in the occupational environment. Measurement of workplace RUA exposure demonstrated that those directly involved in the care of rats experienced the highest RUA exposure of the nine occupational groups studied (animal technicians GM = 23.10 micrograms/m3), dead animals (e.g. post mortem GM = 1.60 micrograms/m3, scientists GM = 0.67 microgram/m3) and rat tissue (e.g. slide production GM = 0.04 microgram/m3). In view of the complexity of rat allergens, RAST inhibition is an appropriate method for the quantification of occupational exposure to rats.

Work related symptoms, sensitisation, and estimated exposure in workers not previously exposed to flour.

Findings are presented from the initial cross sectional phase of a cohort study of employees exposed to flour in bakeries or mills. Of 401 eligible workers in seven sites 344 (86%) were surveyed; symptoms assessed by self completed questionnaire, and sensitisation measured by the response to skin prick tests, were related to intensity of exposure both to total dust and to flour aeroallergen. Among 264 subjects without previous occupational exposure to flour, work related symptoms which started after first employment at the site were related to exposure intensity, especially when exposure was expressed in terms of flour aeroallergen. The relations with eye/nose and skin symptoms were independent of atopic status and cigarette smoking. Positive skin test responses to mixed flour and to alpha amylase were also more frequent with increasing exposure intensity, although this was confounded by atopic status. There was only a weak association between symptoms and specific sensitisation.

Dust and flour aeroallergen exposure in flour mills and bakeries.

As part of an epidemiological study among workers exposed to flour total dust and flour aeroallergen concentrations were measured with personal samplers over a workshift in three large bakeries and four flour mills and packing stations. In the bakeries geometric means for total dust concentrations ranged from 0.4 mg/m3 in the bread wrapping area up to 6.4 mg/m3 at the dough brake. The flour aeroallergen concentrations ranged from 45.5 micrograms/m3 in the bread wrapping area up to 252.0 micrograms/m3 in the confectionary area. In the flour mills and packing stations the concentrations were higher with geometric means for total dust ranging from 0.5 mg/m3 in the office up to 16.9 mg/m3 for hygiene workers in an old mill. The flour aeroallergen concentrations ranged from 101.5 micrograms/m3 for transport workers up to 1728.2 micrograms/m3 for hygiene workers. The relation between total dust and flour aeroallergen concentrations varied for different areas and depended on the use of products other than flour.

Work related symptoms, sensitisation, and estimated exposure in workers not previously exposed to laboratory rats.

Findings are presented from the initial cross sectional phase of a cohort study of employees exposed to laboratory rats. Of 366 eligible workers at four sites 323 (88%) were surveyed; symptoms assessed by self completed questionnaire and sensitisation measured by the response to skin prick tests were related to intensity of exposure both to total dust and to rat urinary aeroallergen. Among 238 workers, without previous occupational exposure to rats, work related symptoms, which started after first employment at the site were related to exposure intensity (expressed either in terms of dust or of aeroallergen) at the time of onset of symptoms. These relations were stronger in atopic subjects but were unrelated to smoking. Positive skin tests to rat urinary extract were also more frequent with increased exposure, a relation found in both atopic subjects and in smokers. There was a strong association between work related symptoms and specific sensitisation.

Reduction of airborne allergenic urinary proteins from laboratory rats.

Allergy and asthma caused by proteins of laboratory animals, particularly rats and mice, are the most important occupational health hazards for the scientists and technicians who work with such animals. The influence of different cage litters, cage design, and stock density on measured rat urinary aeroallergen (RUA) concentrations has been examined in a room housing male rats, to determine practical means to reduce allergen concentration in animal laboratories. Eight hour static air samples were taken at 2 1/min and the RUA concentrations measured by radioallergosorbent test (RAST) inhibition. High RUA concentrations occurred when the animals were housed on wood based, contact litter (geometric mean (GM) sawdust 7.79 micrograms/m3; woodchip 6.16 micrograms/m3). The use of noncontact absorbent pads was associated with a significant decrease in RUA concentrations (GM 2.47 micrograms/m3; p less than 0.0001). Rat urinary aeroallergen concentrations fell more than fourfold when the animals were housed on woodbased, contact litter in filter top cages rather than conventional open top cages (GM filter top 0.33 micrograms/m3; open top 1.43 micrograms/m3; p less than 0.0001). The number of rats (stock density) strongly influenced the RUA concentration and a linear relation was found between the log(e) allergen concentration and stock density under these study conditions. The measurement of airborne particle size on cleaning out days showed that all litter types generated similar sized particles: more than 80% of the RUA was carried on particles larger than 8 microns in diameter for all litter types. The findings suggest that the exposure of animal husbandry personnel to RUA may be substantially reduced by the avoidance of contact litter, the use of filter top cages (where suitable), and by keeping stock density to a minimum.