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62 CPD ACTIVITY Table 3. Clinical trial summary. Trial Patient Intervention Comparison Outcomes SYGMA 1 Age 12 years and older, Mild asthma, 3836 patients Placebo twice daily + terbutaline as needed vs Placebo twice daily + BUD/FOR as needed vs Budesonide twice daily + terbutaline as needed Primary objective – compare BUD/ FOR as needed to terbutaline for asthma symptom control BUD/FOR as needed provides superior asthma symptom control vs terbutaline prn, but inferior to BUD maintenance. Exacerbation rates for BUD and BUD/FOR similar and lower than SABA. BUD/FOR as-needed substantially lowers ICS exposure compared with BUD maintenance. SYGMA 2 Age 12 years and older, Mild asthma at GINA Step 2, 4176 patients Placebo twice daily + BUD/ FOR as needed vs BUD twice daily + terbutaline as needed Primary outcome - annualised rate of SEVERE asthma exacerbations BUD/FOR prn noninferior to BUD for severe exacerbations. Dose of ICS lower with BUD/FOR. Time to 1st exacerbation similar. Change in ACQ-5 score favoured BUD maintenance. Novel START Adults aged 18-75 years with mild asthma using SABA as sole therapy in previous 3 months, 668 patients Salbutamol prn vs BUD twice daily + salbutamol as needed vs BUD/FOR as needed Primary outcome – annualised rate of asthma exacerbations Annualised rate with BUD/FOR lower than SABA as needed, and no difference from BUD maintenance group. Number of severe exacerbations lowest in BUD/FOR group. Mean dose of ICS in BUD/FOR group lower than BUD twice daily. PRACTICAL Age 18-75 years, Asthma using SABA for symptom control relief with or without maintenance ICS in previous 12 weeks, 890 patients BUD/FOR as needed vs BUD twice daily + terbutaline as needed Primary outcome – annualised rate of severe asthma exacerbations Adults with mild to moderate asthma, BUD/FOR as needed more effective at preventing severe exacerbations than BUD maintenance therapy BUD/FOR – budesonide/formoterol; BUD – budesonide; ICS – inhaled corticosteroid; ACQ-5 – Asthma Control questionnaire. FROM PAGE 61 o Reduces the rate of severe flare-ups. o Improves symptom control. o Improves lung function. • As-needed budesonide/formoterol is as good as19,20 or more effective21,22 than regular daily low-dose budesonide in reducing the rate of severe exacerbations. • In the SYGMA trials, regular daily low- dose budesonide was better than as- needed budesonide/formoterol in terms of symptom control, lung function and asthma-related quality of life. However, the differences were not large enough to be considered clinically important.19,20 • As-needed use of budesonide/ formoterol results in substantially lower doses of ICS compared with regular maintenance use of budesonide.19,20, 21,22 Patient discussion The anti-inflammatory reliever approach leverages patients’ inherent relief- seeking behaviour to also deliver inhaled corticosteroids as soon as symptoms appear, and thus reduces the likelihood of the progression of an exacerbation. This approach may address patients’ concerns about the risks of treatment, which causes over-reliance on SABAs and poor adherence to ICS maintenance treatment. The key message for most people with mild asthma is that budesonide/formoterol used as-needed is better than as-needed SABA for asthma symptom control and for reducing the risk of asthma exacerbations, at a substantially low total corticosteroid load and without the need for adherence to 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Relative rate 0.49 (95% CI, 0.33-0.72) p<0.001 Relative rate 1.12 (95% CI, 0.70-1.79) p=0.65 RETAIL PHARMACY • AUG 2020 a twice-daily maintenance schedule. Cost is likely to be a significant barrier to as- needed budesonide/formoterol use. Pharmacists can play a key role in improving asthma control and helping patients understand the risks associated with over-reliance on SABA relievers and poor asthma control. Community pharmacies on average encounter 200 patients with poor asthma control per 0.4 Salbutamol as-needed Budesonide maintenance Budesonide/ formoterol as-needed Figure 3. Annualised exacerbation rate in Novel START trial. Table 4. Asthma Score (Asthma Control Test). 0.175 0.195 1 point 2 points 3 points 4 points 5 points Score In the past four weeks, how much of the time did your asthma keep you from getting as much done at work, school or at home? All of the time Most of the time Some of the time A little of the time None of the time During the past four weeks, how often have you had shortness of breath? More than once a day Once a day three to six times a week Once or twice a week Not at all During the past four weeks, how often did your asthma symptoms (wheezing, coughing, shortness of breath, chest tightness or pain) wake you up at night or earlier than usual in the morning? four or more nights a week two to three nights a week Once a week Less than once a week Not at all During the past four weeks, how often have you used your blue puffer or reliever medication (such as Ventolin, Asmol, Airomir, Apo-Salbutamol or Bricanyl)? three or more times a day one or two times a day two or three times a week Once a week or less Not at all How would you rate your asthma control during the past four weeks? Not controlled at all Poorly controlled Somewhat controlled Well controlled Completely controlled Exacerbation rate per patient per year