Corticosteroid-naive Patients Research Articles

Correlation analysis of T2-weighted images and Medical Research Council scale in corticosteroid-naive patients with Duchenne muscular dystrophy

Because of the necessity of objective instrumental methods for assessing the state of skeletal musculature in patients with Duchenne muscular dystrophy, the aim of our work was to evaluate the correlation between manual methods of assessment of the muscle strength and the results of magnetic resonance imaging (MRI) of the skeletal muscles of lower limbs. We have examined 15 corticosteroid-naive patients with Duchenne muscular dystrophy. Patients were divided into 2 groups: ambulant patients (average age 8.1 years) and non-ambulant patients (mean age 12.7 years). Muscle strength of lower extremities of all patients has been evaluated by Medical Research Council scale and MRI of skeletal muscles of the pelvic girdle, thighs and lower legs has been performed. The following results have been obtained: ambulant patients have been characterized by a high correlation of MRC scale and MRI of the lower extremities in the evaluation of the pelvic girdle and thighs muscles and the total score (pelvic girdle, thighs and lower legs) and salient correlation in the evaluation of the lower legs muscles. Non-ambulant patients have been characterized by moderate correlation in the evaluation of pelvic girdle and thighs muscles, as well as the total score of lower limbs. There was no correlation between MRC and MRI results in the muscles of the lower legs. Magnetic resonance tomography is able to reliably estimate the degree of fatty infiltration in Duchenne muscular dystrophy and is the method of choice in the diagnosis and evaluation of the severity of this disease.

P565 Assessments of clinical efficacy and mucosal healing in ulcerative colitis patients undergoing granulomonocytapheresis at different treatment frequencies

Background: Patients with active ulcerative colitis (UC) are known to have elevated myeloid lineage leucocytes including the CD14+CD16+ monocyte phenotype known to release tumour necrosis factor-α. Accordingly granulomonocytapheresis (GMA) with an Adacolumn has been applied to deplete inflammatory cytokine releasing leucocytes as a remission induction therapy. In general, patients who respond well continue responding and favour GMA over pharmacologics. However, published data indicate that patients with extensive deep ulcers and loss of the mucosal tissue at the affected sites may not respond well to GMA, while steroid naïve patients respond well. We have focused on GMA frequency and long term efficacy as supported by endoscopic findings. Methods: In a retrospective setting, and with interest on long term mucosal healing, we assessed the efficacy of the Adacolumn GMA in patients with active UC treated at different GMA frequencies in the past 10 years. In our data base, we found 99 corticosteroid naive patients who had received GMA at one session per week (n=18, group 1), at 2 to 4 sessions per week (n=31, group 2) or daily (intensive) GMA (n=50, group 3). Each patient could have received up to 11 GMA sessions. Initial efficacy evaluations were undertaken within 10 days following the last GMA session. Clinical activity index (CAI) ≤4 meant remission, while Mayo 0 or 1 meant mucosal healing. The included patients had been followed for ≥12 months on maintenance mesalamine. Results: The average baseline CAI in groups 1 to 3 were 7.9, 7.8, and 8.4, respectively; the number of GMA sessions were 9.1, 9.7 and 10.1 sessions, respectively; the GMA treatment periods were 55.1, 26.5 and 15.5 days, respectively. The mean CAI after the conclusion of GMA treatment courses were 2.5±2.7, 3.4±3.1 and 3.5±2.7, respectively. The rates of mucosal healing were 76.9%, 60.% and 61.8%, respectively. At 12 months, 40.0% in group 1, 57.1% in group 2 and 61.9% in group 3 had maintained mucosal healing. No GMA related serious adverse event was observed. Conclusions: This efficacy evaluation undertaking in steroid naïve patients with active UC showed that for an equal number of GMA sessions, the clinical efficacy was not significantly affected by the frequency of GMA sessions, but the time to remission and the rate of mucosal healing at 12 months were significantly better for intensive GMA. However, the efficacy outcomes in our 99 patients are higher than reported for GMA in patients with severe UC refractory to the current pharmacologicals, reflecting the fact that GMA is more effective in steroid naïve patients who have mild or moderately active UC, but not so effective in patients with severe UC in whom drug therapy has failed.

CLINICAL AND IMMUNOLOGICAL EFFECTS OF CARBOCYSTEINE IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Background: Chronic obstructive pulmonary disease (COPD) is one of the commonest diseases characterized by persistent distal airways inflammation. Thus, anti-inflammatory therapy should be the basis of COPD treatment. There is only limited evidence supporting the efficacy of mucolytics like carbocysteine in the preventing COPD exacerbations in inhaled corticosteroid-naive patients. Aim: To study clinical and immunological effects of carbocysteine in COPD. Materials and methods: During first 2 months, 30 patients with stage II COPD (mean age 55.9±1.2 years old) were treated with inhaled glucocorticosteroids and beta2-adrenoceptor agonists ‘as required’. Thereafter, the standard therapy was continued in 15 patients; in other 15 patients carbocysteine 1500 mg/day was added. Immune status was studied bi-monthly in all patients: to detect lymphocytes with expression of CD3, CD4, CD8, CD72-antigens and CD23, CD71, CD95 and HLA-DR activation markers, monoclonal antibodies were used. Quality of life was assessed using adapted Russian version of St. George’s Respiratory Questionnaire (SGRQ). Results: Compared with the anti-inflammatory therapy, adding carbocysteine to standard therapy of COPD was associated with significantly better quality of life after 4 months of therapy (less negative changes of symptoms and activity scores and improvement of psycho-social function: changes of relevant SGRQ scores were -3.4 and -8.0; -1.9 and -3.8; 0.4 and -0.76, respectively). After 4 months, carbocysteine-treated patients demonstrated better improvements in shortness of breath, cough and sputum scores compared with the control group (2 and 2.2; 1.5 and 1.9; 0.8 and 1.2, respectively). In carbocysteine group, clinical symptoms improvement correlated with positive changes of immunological status. The patients demonstrated greater significant elevation of total T-lymphocytes (especially CD8+-cells), decreased B-cells and increased expression of CD95-antigen compared with the standard therapy group. Conclusion: Carbocysteine may be recommended as an obligate part of therapy in COPD patients.

Altered therapeutic response towards inhaled corticosteroids in asthmatics –smokers with mild asthma

The exposure to tobacco smoke could cause bronchoconstriction and acute asthma attack. Smoking asthmatics have an insufficient therapeutic response to the standard therapy and unsatisfactory improvement of the respiratory function. In a randomized parallel study, a therapeutic response to inhaled fluticasone propionate in a dose of 250 µg twice per day was determined in 38 asthmatics with mild asthma, smokers and nonsmokers. Short-acting ß2 agonist (salbutamol) in a dosage of 0.1 mg/per inhaled dose was used as a rescue medication when needed. In patients, asthma was detected with a positive metacholine test and/or positive bronchodilatator response of > 12% with ≥ 200 ml increase of FEV1. They were randomized in two groups according to sex, age and starting values of FEV1. Before and after 6 weeks of treatment with fluticasone propionate of the previously corticosteroid-naive patients, lung function test (spirometry) was performed. A statistically significant effect (p<0.05) was achieved during the fluticasone propionate therapy in a group of non-smoking asthmatic patients. The same effect was not seen in the group of smoking asthmatics. Although the percentage of elevated FEV1 values was small, it was satisfactory because of the starting FEV1 values in patients with mild asthma. More studies are needed in asthmatics determining the asthma symptom score, the number of night awakenings due to asthma, the asthma exacerbations and the frequency of rescue therapy usage which will define the altered therapeutic response to inhaled corticosteroids in smoking asthmatics.

The influence of inhaled corticosteroids on asthma control test in smokers and non-smokers with asthma

Smoking in asthmatics is responsible for the worsening of asthma symptoms, more frequent asthma exacerbations and hospitalizations and lowered quality of life. In smoking asthmatics the designated doses of the inhaled corticosteroid treatment are usually insufficient to accomplish total asthma control. Out of 54 screened adult patients up to 50 years old with mild asthma, 38 were involved in the study. They were divided in two groups: smokers and non-smokers. They received a total daily dosage of 500 µg of inhaled fluticasone propionate. A rescue medication, a short-acting ß2 agonist (salbutamol) in a dosage of 0.1 mg/per inhaled dose, was used when needed. Asthma was diagnosed by a positive metacholine provocation test and/or a positive bronchodilatator response. An asthma control test i.e. the ACT-TM questionnaire was performed before the beginning of the study and 6 weeks after the treatment with fluticasone propionate of the previous corticosteroid-naive patients. A statistically positive response (p<0.05) was reached in favor of non-smoking asthmatics. It can be concluded that ACT is a reliable tool to assess the effect of the topical corticosteroid treatment in non-smoking and smoking asthmatics. An achievement of better asthma control could be expected among both of the examined groups, but the effect of the intervention in the therapy is estimated to be more expressed within the group of asthmatic non-smokers. In smoking asthmatics there is a need for other therapeutic modalities such as increasing the dosage of inhaled corticosteroids, usage of combination therapy and/or adding low doses of aminophylline.

Fatigue in Patients with Early-Stage Systemic Lupus Erythematosus Before Receiving Corticosteroid Therapy: A Prospective Cross-Sectional Study

Fatigue has been intensively studied in patients with systemic lupus erythematosus (SLE). However, previous studies have mostly included patients with long-term disease who have been treated with corticosteroids. We investigated fatigue in corticosteroid-naive patients with early-stage SLE.

Psychological distress in corticosteroid-naive patients with systemic lupus erythematosus: A prospective cross-sectional study

Psychological distress, such as depression and anxiety, has been intensively studied in patients with systemic lupus erythematosus (SLE). However, those studies have mostly included patients who were treated with corticosteroids, which might themselves induce mood disturbances. We investigated psychological distress in corticosteroid-naive patients with SLE who did not exhibit any overt neuropsychiatric manifestations. Forty-three SLE in-patients with no current or past abnormal neuropsychiatric history participated in the study. Patients and 30 healthy control subjects with similar demographic and personality characteristics were administered a comprehensive battery of psychological/neuropsychological tests. The Profile of Mood States (POMS) was used to assess depression and anxiety. Results of clinical, laboratory, and neurological tests were compared with regard to their presence. Prevalence of depression was higher in patients (n = 11, 25.6%) than in controls (n = 2, 6.7%; p = 0.035), although prevalence of anxiety did not differ across groups (patients: 34.9%, n = 15; controls: 16.7%, n = 5; p = 0.147). Using multiple logistic regression analysis, we identified avoidance coping methods (OR, 1.3; 95% CI 1.030-1.644; p = 0.027) as an independent risk factor for depression. Our results indicate that depression presents more frequently in corticosteroid-naive patients with early-stage, active SLE than in the normal population, but anxiety does not. Depression may be related to psychological reactions to suffering from the disease.

Neurocognitive impairment in corticosteroid-naive patients with active systemic lupus erythematosus: a prospective study.

Neurocognitive impairment (NCI) has been intensively studied in patients with systemic lupus erythematosus (SLE). However, those studies have mostly included patients who were treated with corticosteroids, which may itself induce NCI. We investigated NCI in corticosteroid-naive people with SLE who did not exhibit any overt neuropsychiatric manifestations. Forty-three inpatients with SLE who had no current or past neuropsychiatric history participated in the study. Patients and 30 healthy control subjects with similar demographic characteristics were given a 1-h battery of neuropsychological tests. NCI was defined as scores at least 2 SD below the mean of the healthy control group on at least 2 of the 7 neurocognitive domains. Results of clinical, laboratory, and neurologic tests were compared regarding the presence of NCI. NCI was identified in 12 patients (27.9%) with SLE and in 2 control subjects (6.7%). Patients with SLE showed a significant impairment compared with controls on tasks assessing immediate recall, complex attention/executive function, and psychomotor speed. We identified psychomotor speed (Digit Symbol Substitution Test) as the factor that best differentiated the 2 groups. Further, we identified the score of the SLE Disease Activity Index 2000 as an independent risk factor for NCI in patients with SLE. We conclude that reduced psychomotor speed is an SLE-specific pattern of NCI. Verbal-memory deficits that have been reported in patients with SLE were not evident among patients who were corticosteroid-naive. Our results indicate that impaired psychomotor speed may be added to the symptoms of early SLE.

Infliximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn' Disease

Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-α has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX. Twenty-two patients with a CD activity index (CDAI) of 194.2±92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their first IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. CDAI significantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-β1 (p<0.01), and 'regulated on activation, normal T cell expressed and secreted' (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-α (p<0.04), IL-6 (p<0.03), interferon (IFN)-γ (p<0.04), IFN-γ-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage inflammatory protein-1β (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-γ)/Th2 (IL-4) ratio (p<0.03). IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naïve Th0 lymphocytes to Treg. This knowledge should have clinical relevance.

W1487: Corticosteroid Naive Patients and Patients With the First Ulcerative Colitis Episode and Short Duration of Disease Are Most Likely to Respond Well to Therapeutic Leucocytapheresis With the Adacolumn

The efficacy of infliximab has validated the notion that inflammatory bowel disease (IBD) like ulcerative colitis (UC) is exacerbated and perpetuated by specific cytokines, notably tumour necrosis factor (TNF)-α. Further, patients with active UC often harbour elevated and activated granulocytes/monocytes (GM), which are known to release TNF and other cytokines. Accordingly, several groups have investigated the efficacy of extracorporeal GM adsorption (GMA) in patients with IBD, but have reported unmatched efficacy outcomes, ranging from an impressive 85% (Cohen RD. Gastroenterology 2005;128:235-6) to an insignificant level (Sands BE, et al. Gastroenterology 2008;135:400-9). However, most hitherto studies recruited sub-groups of patients who had failed to respond to conventional medications and made no attempts to identify responders based on patients' baseline characteristics.

W1123 Adsorptive Depletion of Circulating α4 Integrin Hi and Cx 3Crl Hi Expressing Proinflammatory Monocytes in Patients with Active Ulcerative Colitis

BACKGROUND AND AIM: Circulating monocytes exist as two main functionally distinct phenotypes, the CD14hiCD16“classical” phenotype and the CD14+CD16+ “proinflammatory” phenotype for releasing large amounts of tumour necrosis factor (TNF)-α. Further, the CD14+CD16+ phenotype is elevated by up to 2 fold (or more) in patients with inflammatory bowel disease (IBD) and is suspected to have a major role in the immunopathogenesis of IBD as this phenotype is readily recruited to inflammatory as well as to non-inflammatory mucosal tissues where they differentiate into cytokine producing resident macrophages or dendritic cells. Accordingly, selectively depletion of CD14+CD16+ monocytes should be a major research objective.METHODS: Seven corticosteroid naive patients with active ulcerative colitis (UC), Lichtiger's clinical activity index (CAI) = 8.7±1.3, and 7 healthy subjects as controls were included. In patients with UC, granulocyte/monocyte adsorption (GMA) was done with an Adacolumn that selectively adsorbs leucocytes of the myeloid lineage. Peripheral blood from all subjects at baseline and from patients immediately after the first GMA session was processed. Isolated monocytes were subjected to extensive fluorescenceactivated cell sorter (FACS) analyses. RESULTS: The 7 patients with UC achieved clinical remission (CAI≤4) after 5-10 GMA sessions. GMA was associated with a striking fall in the ratio (%) of CD14+CD16+/CD14hiCD16monocytes, from 10.0±1.4 to 3.0±0.9 (P<0.05), indicating selective depletion of CD14+CD16+ monocytes. Further, FACS analyses revealed that the expressions of the adhesion molecules α4 integrin, 374.8±26.1 mean fluorescence intensity (MFI) and CX3CR1, 49.5±4.6MFI were significantly (P<0.05) high on CD14+CD16+ monocytes as compared to CD14hiCD16monocytes, 169.2±17.2 MFI and 33.2±3.6 MFI, respectively. Additionally, GMA increased the ratio of the “immature” CD14hiCD16-CCR2low monocytes from 3.74±0.62 MFI to 8.11±0.56 MFI (P<0.05), indicating that GMA was followed by an influx of immature monocytes from the bone marrow into the circulation. CONCLUSIONS: To our knowledge, this is the first report of detecting elevated levels of α4 integrin on the proinflammatory CD14+CD16+ monocytes as compared to the classical CD14hiCD16monocytes. A high level of α4 integrin on the CD14+CD16+ monocytes might promote extravasation of these myeloid cells to the mucosa as significant sources of TNFα. GMA was very effective in depleting the CD14+CD16+ monocytes and at the same time, it was associated with an increase in CD14hiCD16-CCR2low monocytes. These data should contribute to a better understanding of immune pathology in patients with IBD.

A Clinical Electrophysiological Study of Emotional Lability in Patients With Systemic Lupus Erythematosus

A Clinical Electrophysiological Study of Emotional Lability in Patients With Systemic Lupus Erythematosus

Risedronate for prevention of bone mineral density loss in patients receiving high-dose glucocorticoids: a randomized double-blind placebo-controlled trial

This 6-month randomized double-blind placebo-controlled trial shows that risedronate is well tolerated and effective in improving lumbar spine BMD and reducing loss of BMD at the hips in patients receiving high-dose prednisolone. Bisphosphonates have proven benefits in patients receiving chronic low-dose glucocorticoids. However, whether they are effective in preventing bone mineral density (BMD) loss during periods of high-dose glucocorticoid treatment is unclear. The objective of this paper is to study the efficacy of risedronate in preventing bone mineral density (BMD) loss in users of high-dose glucocorticoids. Adult patients with medical diseases treated with high-dose prednisolone (>0.5 mg/kg/day) were randomized to receive risedronate (5 mg/day) or placebo for 6 months in a double-blind manner, along with elemental calcium (1,000 mg/day). Changes in BMD were studied. One hundred and twenty patients were recruited (82 women, age 42.8 +/- 14.3 years, 63% corticosteroid-naive, 30% women postmenopausal) and 103 completed the study. Baseline clinical characteristics and BMD were similar in the risedronate and placebo groups. At 6 months, a significant gain in spinal BMD was observed in the risedronate group (+0.7 +/- 0.3%; p = 0.03) but a drop was detected in the placebo group (-0.7 +/- 0.4%; p = 0.12). After adjustment for baseline BMD, age, gender, body mass index and cumulative prednisolone dosages, the inter-group difference in spinal BMD remained significant (1.4%; p = 0.006). Both groups had a significant drop in hip BMD, but the magnitude was greater in the placebo arm (-0.8 +/- 0.4% in risedronate versus -1.3 +/- 0.5% the in placebo). No new fractures developed. Subgroup analysis of corticosteroid-naive patients yielded similar results. Upper gastrointestinal adverse events were numerically more frequent in the risedronate group. Risedronate improves spinal BMD in users of high-dose glucocorticoids.

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn’s disease

Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

Leukocyte adsorptive apheresis for the treatment of active ulcerative colitis: A prospective, uncontrolled, pilot study

Background & Aims: Active ulcerative colitis (UC) is characterized by infiltration of activated granulocytes and monocytes/macrophages (GM) within the large bowel mucosa. GM are major sources of inflammatory cytokines, and in UC they are elevated with increased survival time. We investigated the possibility that reducing the level of these cells might promote remission of active UC. Methods: Thirty-one patients with active corticosteroid refractory (refractory) UC, mean age of 42 years, duration of UC 6 years, clinical activity index (CAI) of 15, disease activity index (DAI) of 10, and 8 corticosteroid naive patients (naive), mean age of 36 years, duration of UC 2 years, CAI of 11, DAI of 8 were recruited. Each patient was treated with up to 11 cycles of granulocyte and monocyte adsorptive apheresis over 11 weeks by using a 335-mL capacity column filled with cellulose acetate beads that adsorb GM. Results: At week 12, 81% of refractory (CAI, 3; P < 0.001 and DAI, 4; P < 0.001) and 88% of naive (CAI, 1; P = 0.012 and DAI, 3; P = 0.011) patients achieved remission. Early relapse was not a feature, and at 12 months, 26 of 33 patients had maintained their remission. The treatment was well tolerated, and no severe side effects were observed. Conclusions: The outcome of this study suggests that reduction of circulating granulocytes and monocytes results in alleviation of inflammation and promotes clinical remission in patients with severe active UC that has not responded to intensive corticosteroid treatment. These data suggest that formal controlled studies are warranted. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2003;1:28-35

Efficacy of budesonide in inhaled corticosteroid—naive patients and patients with mild persistent asthma

Background: Patients with mild intermittent or mild persistent asthma represent 70% of asthma sufferers. Inhaled corticosteroids (ICSs) are the mainstay of treatment for persistent asthma, although many of the early clinical studies of these drugs included only patients with moderate to severe asthma.Objective: This article reviews the literature on the efficacy of budesonide in the treatment of mild persistent asthma, including newly diagnosed ICS-naive patients.Methods: Published data were identified by a MEDLINE search of the English-language literature from 1992 to 2002 using the terms budesonide plus efficacy or safety, both with and without the terms fluticasone or beclomethasone. An AstraZeneca reference database was also used to identify publications from the same period. Controlled, randomized studies that included patients with mild persistent asthma and early-treatment intervention were selected for inclusion.Results: Inhaled budesonide has been used for almost 20 years in the treatment and control of moderate to severe asthma. Studies involving patients with mild persistent asthma have demonstrated significant improvements in peak expiratory flow (PEF) rates (P < 0.01) and forced expiratory volume in I second (P < 0.016) values for adult, adolescent, and pediatric patients treated with budesonide compared with placebo. Budesonide therapy is effective when given once or twice daily via dry powder inhaler or nebulizer, even at a low starting dose (200 μg/d). No significant adverse events have been reported with budesonide within the dose range used to treat mild persistent asthma (200 to 400 μg/d). Significant improvements in PEF rates (P < 0.01) and significant reductions in the risk of exacerbations and the number of days with poorly controlled asthma have been reported for ICS-naive patients treated with budesonide compared with placebo (both P < 0.001). In the primary care setting, mild persistent asthma may be undertreated. Patients with mild persistent asthma benefit significantly from early treatment with budesonide (P < 0.05).Conclusions: Budesonide is effective and well tolerated in the treatment of mild persistent asthma in adults and children, including many patients whose primary care physicians do not think they require daily ICS treatment.

Cost-Efficacy Analysis of Fluticasone Propionate versus Zafirlukast in Patients with Persistent Asthma

To compare the relative value of an inhaled corticosteroid, fluticasone propionate 88 microg twice daily, versus an oral leukotriene receptor antagonist, zafirlukast 20 mg twice daily, in patients with persistent asthma currently receiving short acting beta2-agonists alone. A cost-efficacy analysis using resource utilisation and clinical data obtained prospectively from a multicentre, randomised, double-blind, double-dummy, placebo-controlled 12-week clinical trial conducted in the US. Third-party payor. A total of 451 corticosteroid-naive patients with persistent asthma were treated with either fluticasone propionate 88 microg twice daily or zafirlukast 20 mg twice daily. All patients were given salbutamol (albuterol) to be used as rescue medication. Data were examined using intent-to-treat analysis. Mean daily per person cost-efficacy ratios using improvement in forced expiratory volume in 1 second (FEV1) [> or = 12% increase from baseline] were $US 3.47 for fluticasone propionate compared with $US 7.81 for zafirlukast (1999 values). The mean daily per person cost-efficacy ratios for symptom-free days obtained were $US 5.51 for fluticasone propionate compared with $US 14.98 for zafirlukast. These cost-efficacy ratios remained in favour of fluticasone propionate after a robust sensitivity analysis. Treatment with fluticasone propionate 88 kg twice daily was the most cost effective treatment compared with zafirlukast 20 mg twice daily in this 12-week clinical trial. This analysis supports the use of fluticasone propionate 88 microg twice daily as first-line treatment in patients with persistent asthma previously treated with short-acting beta2-agonist alone.

Time to onset of effect of fluticasone propionate in patients with asthma

Background: The effectiveness of inhaled glucocorticoids in the treatment of asthma is well documented; however, times to onset and maximal treatment effects of these agents have been poorly described. Objective: We sought to determine the time to onset of effect and the time to the best observed effect of inhaled fluticasone propionate (FP) in patients with asthma. Methods: Data from 8 randomized, double-blind, placebo-controlled clinical trials of at least 8 weeks’ duration were analyzed. Corticosteroid-naive patients (n = 1461) were treated with either FP (25 μg to 500 μg) or placebo twice daily. Efficacy evaluations included morning peak expiratory flow (PEF), asthma symptom scores, supplemental albuterol use, and FEV 1 . Results: Statistically significant improvements in PEF, asthma symptom scores, and supplemental albuterol use were observed beginning on day 1 of treatment in the FP group versus the placebo group ( P < .001); significant increases in FEV 1 were observed at the first measurement at week 1 ( P < .001). The best observed effect occurred within 3 weeks of the start of FP treatment for PEF (+36 L/min) and FEV 1 (+0.52 L) and within 2 weeks for reduction in supplemental albuterol use and asthma symptom scores. Patients with the most severe airflow obstruction had the greatest change in PEF (+56 L/min) and fastest time to 50% of best observed effect (3 days) compared with patients with mild or moderate airflow obstruction; however, time to best observed effect was similar in the 3 groups (20 to 27 days). Conclusion: In patients with asthma, the onset of significant benefit of FP on PEF, symptoms, and rescue albuterol use occurred within 1 day of the start of therapy. FEV 1 improved within 1 week of the start of therapy (the first measurement after randomization). There was no effect of sex, age, or dose of FP on the time to response. The best observed response in PEF varies with the degree of baseline airflow obstruction; however, the degree of airflow obstruction has no effect on the time to best observed response. (J Allergy Clin Immunol 1999;103:780-8.)

Effect of inhaled corticosteroids on bronchial responsiveness in patients with “corticosteroid naive” mild asthma: a meta-analysis

BACKGROUNDInhaled corticosteroids are the most efficacious anti-inflammatory drugs in asthma. International guidelines also advocate the early introduction of inhaled corticosteroids in corticosteroid naive patients. A study was undertaken to assess...

Cost Effectiveness of Fluticasone and Budesonide in Patients with Moderate Asthma

The objective of this study was to assess the relative cost effectiveness of fluticasone via metered dose inhaler and budesonide via Turbuhaler((R)) in corticosteroid-naive patients with moderate asthma from a third-party payer perspective (German Sickness Funds). A retrospective economic assessment of direct medication costs of treatment was performed on data from a prospective, randomised, parallel group, 6-week clinical trial. 457 corticosteroid-naive patients between the ages of 18 and 70 years with moderate asthma were included in the intention-to-treat analysis. The fluticasone group had a higher proportion of successfully treated patients (those with a peak expiratory flow rate improvement of >/=10%) [47 vs 42%], a higher average proportion of symptom-free days (40 vs 34%) and lower direct healthcare costs [1997 Deutschmarks (DM)] per day (DM4.23 vs DM5.19) than the budesonide group. Therefore, the daily costs per successfully treated patient (DM9.00 vs DM12.36) and the cost per symptom-free day (DM10.58 vs DM15.26) were both lower with fluticasone than with budesonide. Sensitivity analysis demonstrated that these results were relatively robust over a wide range of plausible assumptions. These results showed that from the perspective of a third-party payer, fluticasone was more cost effective than budesonide over the 6-week study period.