Prescribing for patients with COPD Evidence Update Emma Blanden- Pharmacist

Inhaled drug treatment of COPD- outcomes Reduce symptoms Improve quality of life Reduce exacerbations Reduce deterioration in lung function Reduce mortality

Reducing symptoms Most drugs improve symptoms Assess & record response to treatment–MRC score, ability to do activities of daily living, exercise capacity Review diagnosis Inhaler technique Trial of therapy- if it doesn’t work don’t be afraid to stop it

Reducing exacerbations LAMAs & LABAs POET-COPD trial 2011 Tiotropum vs Salmeterol RCT 7376 patients time to first exacerbation greater with tiotropium 187 days vs 145 days patients continued treatment with ICS throughout study (not NICE) no info in patients with mild COPD no info about comparisons with other LABAs Tiotropium may be more effective than salmeterol in terms of exacerbations but the evidence is currently unclear

Reducing exacerbations- ICS

Reducing exacerbations The “frequent exacerbator’’ (more than 2 exacerbations/ year) Best predictor of having another exacerbation is frequency of past exacerbations

Effects on lung function Limited evidence of clinically significant impact for any drug Tiotropium UPLIFT trial- clinically important amount?? Significant person to person variation & no good predictors of who most likely to deteriorate Stopping smoking reduces decline

Reducing mortality SAMAs – increased risk of mortality? SABAs- no increased risk LABAs- no evidence of impact LAMAs- UPLIFT trial showed no impact (but non- significant trends towards reducing mortality) ICS- Cochrane review- no impact

Tiotropium (Spiriva) Respimat-safety significantly increased risk of mortality greatest risk seen in patients with more severe COPD and at a higher daily dose. risk was more evident for cardiovascular death Excess risk not apparent with Handihaler Current MHRA Advice: Use Respimat with caution in patients with known cardiac rhythm disorders. Remind patients on tiotropium not to exceed the recommended doses

Inhaled corticosteroids- risks 1 extra case of pneumonia for every 47 people treated with ICS over 1 year 1 person will develop diabetes for every 21 patients treated with ICS over 5 years 1 extra fracture for every 80 people treated with ICS over 3 years

Drug treatment of COPD-outcomes Reduce symptoms Improve quality of life Good evidence for all inhaled drugs Reduce exacerbationsEvidence for some drugs Reduce deterioration in lung function Limited evidence Reduce mortalityLittle evidence

Inhaled drug treatment – what are we trying to achieve? Improving symptoms Most drugs improve symptoms Inhaler technique Record severity and symptoms & assess response to treatment Trial of inhaler therapy – if it doesn’t work stop it and try another Reducing exacerbations Tiotropium and LABAs reduce exacerbations ICS reduce exacerbations – but side effects Identify “frequent exacerbators’’ – most likely to benefit from treatment Review ICS treatment for patients with mild- moderate disease without exacerbations Before starting ICS consider potential benefits treatment and risks of harm for individual patient

COPD ‘Value’ Pyramid What we know…. Cost/QALY Triple Therapy £35,000- £187,000 LABA £8,000/QALY Tiotropium £7,000/QALY Pulmonary Rehabilitation £2,000-8,000/QALY Stop Smoking Support with pharmacotherapy £2,000/QALY Flu vaccination £?1,000/QALY in “at risk” population

Stage 2: Moderate FEV 1 ≥ 50% Stage 2: Moderate FEV 1 ≥ 50% Formoterol 12 microg twice daily Easyhaler £12 Atimos MDI £18 or Salmeterol 50 microg Accuhaler /MDI twice daily £30 Tiotropium (Spiriva Handihaler®) 18 microg once daily £32 or Glypyrronium (Seebri Breezhaler®) 50 microg once daily £28 or Aclidinium (Eklira Genuair®) 400 microg twice daily £29 discontinue ipratropium LABA LAMA

New LAMAs similar efficacy to tiotropium no robust evidence of any advantage over tiotropium or other long- acting bronchodilators no long term data on effectiveness or safety APC advice: as an option for new patients, do not switch Aclidinium (Eklira Genuair®) twice daily Glypyrronium (Seebri®) once daily

Combined inhalers BDP equivalence (note the dose of long acting bronchodilator (LABA) may vary) BDP equivalence Daily dose Licensed for use in COPD Cost for 30 days Expected no inhalers/ yr Fostair® (BEC + formeterol) 100/6 MDI 2pBD (120dose) mcgno£ Symbicort ® (BUD + formeterol) 400/12 1pBD (60 dose) 800mcgyes£ Symbicort® (BUD + formeterol) 200/6 2pBD (120 dose) 800mcgyes£ Flutiform® ( FLU + formeterol) 250/10 MDI 1pBD (120 dose) 1000mcgno£ Seretide ® 250/50 ACCUHALER 1P BD (60 dose) 1000mgno£ Flutiform® ( FLU + formeterol) 250/10 MDI 2pBD (120 dose) 2000mgno£ Seretide ® 500/50 ACCUHALER 1p BD (60 dose) 2000mgyes£

Mucolytic therapy Consider in people with a chronic productive cough and continue use only if symptoms improve. Mucolytics do not prevent exacerbations. Many patients end up on long-term mucolytics after starting during an acute exacerbation. Stop mucolytics routinely after an exacerbation and reassess before re-starting. Carbocisteine capsules or oral liquid: 750mg three times a day for 4 weeks (capsules 375mg: Liquid 250mg/5mls) If no benefit after 4 weeks- stop treatment. If beneficial continue with 750mg twice a day.

Treatment of COPD exacerbations Increase frequency of bronchodilator use Prednisolone 30mg once daily for 7-14 days Antibiotics 5-7 days: See Worcestershire Guidelines for Primary Care Antimcirobial PrescribingWorcestershire Guidelines for Primary Care Antimcirobial Prescribing 1 st line- amoxicillin 500mg tds or doxycycline 200mg stat then 100mg daily. 2 nd line- clarithromycin 500mg bd 3 rd line - co-amoxiclav 625 mg tds If resistance risk factors (co-morbid disease, severe COPD, frequent exacerbations, antibiotics in last 3 months) Standby home packs