Inhaled Corticosteroids and the Risk of

Pneumonia

Tobias Welte

Department of Respiratory Medicine

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

ICS in COPD – A Risk Factor for CAP?Rate of pneumonia in ICS Studies

Placebo Salmeterol or

Tiotropium

Fluticason Seretide

(SAL/FLU)

TORCH1

3-year Follow-Up

12.3% 13.3% 18.3%* 19.6%*

VIVACE2

44 week Follow-Up

7 (=1.5%) 23 (=5.7%)

INSPIRE3

2-year Follow-Up

24 (=4%) 50 (=8%)§

1Calverley P. NEJM 2007; 356: 775-89; 2Kardos P. AJRCCM 2007; 175: 144-49; 3Wedzicha JA; AJRCCM 2008; 177: 19-26

*p< 0.001 vs. Placebo; § Hazard Ratio for time to reported pneumonia 1.94 (p=0.008)

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

Steroid Use in COPD - A Risk Factor for CAP?

• 175,906 patients with COPD, 23,942 hospitalized for pneumonia (1.9 per 100 per year)

• Matched to 95,768 control subjects.

• The adjusted RR of hospitalization for pneumonia associated with current use of ICS was 1.70 (95% CI), 1.63–1.77) and 1.53 (95% CI, 1.30–1.80) for pneumonia hospitalization followed by death within 30 days. The RR of hospitalization

– greatest with the highest doses of ICS equivalent to fluticasone at 1,000 µg/day or more (RR, 2.25;95% CI, 2.07–2.44).

• All-cause mortality was similar for patients hospitalized for pneumonia, whether or not they had received ICS (7.4 and 8.2%, respectively)

Ernst P. AJRCCM 2007; 176: 162-66

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

• New-user cohort of patients with COPD treated during 1990–2005.

• A nested case–control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use

– adjusted for age, sex, respiratory disease severity and comorbidity.

• 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year)

• Use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69)

• The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months

• The rate of serious pneumonia was higher with fluticasone (RR 2.01), increasing with the daily dose, but was much lower with budesonide (RR 1.17)

Steroid Use in COPD - A Risk Factor for CAP?Suissa S. Thorax 2013; 68: 1029-36

Fluticasone

Budesonid

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

Steroid Use in COPD - A Risk Factor for CAP?Suissa S. Thorax 2013; 68: 1029-36

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

Budesonide and the Risk of Pneumonia in COPD – a Meta-Analysis

D SIn et al., Lancet 374:712-719, 2009

Risk of pneumonia as SAE

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

BMJ 2013;346: f3306

44

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

Cumulative number of pneumonia events and admissions to hospital because of pneumonia per patient over nine

years after index date

Janson C. et al. BMJ 2013;346: f3306

44

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

Pneumonie related Mortality Janson C. et al. BMJ 2013;346: f3306

44

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

• Clinical and 5-year follow-up data were collected on all adults aged ≥65 years with pneumonia over a period of 2 years.

• Nested case-control design matched on age, sex, and COPD

– Cases• patients with recurrent pneumonia ≥30 days

after initial episode – Controls

• free of pneumonia

• 653 recurrent pneumonia cases were matched with 6244 controls

– Mean age was 79 years– 3577 (52%) male– 2652 (38%) had COPD– 2294 (33%) ever used ICS

• 123 of 870 (14%) current ICS users had recurrent pneumonia compared to 395 of 4603 (9%) never-users (adjusted odds ratio, 1.90; P < .001; number need to harm = 20)

• no association between past use of ICS and pneumonia: 9% of past users versus 9% never-users (P = .36).

Steroid Use in COPD - A Risk Factor for CAP?

Eurich DT. CID 2013; 57: 1138-44

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

Eurich DT. CID 2013; 57: 1138-44

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

• Primary care data from The Health Improvement Network in the UK• People with asthma with pneumonia or lower respiratory tract

infection• Age- and sex-matched control subjects. • The highest strength of ICS ( >1,000 µg) had a 2.04 increased risk of

pneumonia or LTRI compared with no prescription for ICS within the previous 90 days

Steroid Use in COPD - A Risk Factor for CAP?

McKeever T. Chest 2013; 144: 1788-94

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

ICS – Risk for Tuberculosis

• Case control study in Korea using the national health care data base

• 853 439 Pts prescribed ICS for the first time (2007 bis 2010)

• Pts with a first diagnosis of TB after starting ICS were included

• Data were adjusted for age, gender, Asthma-/COPD Diagnosis and time since start of ICS

• 4139 TB were diagnosed and compared with 20 583 controls

• ICS increased the likelihood for Tb (adjusted OR 1.20) significantly

• The assoziation was dose dependend (p <0.001)

Chang-Hoon L. et al. Thorax 2013;68:1105–1113.

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

• Case-control study in adults in Denmark with microbiologically confirmed NTM pulmonary disease between 1997 and 2008

• 10 matched population controls per case.• Chronic respiratory disease was associated with a 16.5-fold

increased risk of NTM pulmonary disease• Adjusted OR for NTM disease was 15.7 for COPD, 7.8 for

asthma, 9.8 for pneumoconiosis, 187.5 (95% for bronchiectasis, and 178.3 for tuberculosis history

• ORs were 29.1 for patients with COPD on current ICS therapy and 7.6 for patients with COPD who had never received ICS therapy

• ORs increased according to• ICS dose from 28.1 for low-dose intake to 47.5 for high-dose

intake (more than 800 μg/day)• OR was higher for fluticasone than for budesonide

ICS – Risk for NTM

CAndréjak C. et al. Thorax 2013;68: 256–62.

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

ICS and PneumoniaPleural Effusion

• Single center cohort study in Spain in 3,612 CAP patients • 633 Pts (17%) were treated with ICS before CAP was diagnosed (COPD

54%; Asthma, 13%)• Incidence of a parapneumonic pleural effusion lower in ICS patiens

compared to non ICS patients (5% vs. 12%; P < 0.001). • ICS pretreatment was associated with higher glucose and pH and

lower protein and LDH concentraitions in the pleural effusion

Sellares J. et al. AJRCCM 2013: 1241-48.

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014

Sellares J. et al. AJRCCM 2013: 1241-48.

45

ICS and PneumoniaPleural Effusion

Welte – ICS and pneumonia 11.10.2014Welte – ICS and pneumonia 11.10.2014