Table. Summary of studies on SCS-induced morbidity in asthmatic populations.
| Study | Database, region | Population and definition | Comparison by SCS exposure | Observation duration | Positive findings* |
|---|---|---|---|---|---|
| Lefebvre et al. (2015)55 | Health insurance claims database (1997–2013: Medicaid), US | • Severe asthma (≥ 12 years old): ≥ 2 administrative charges associated with a diagnosis of asthma and had > 6 months of continuous chronic SCS use (with daily doses of > 5 mg of prednisone equivalent with no gap of 14 days or more between 2 SCS claims) | • Chronic low dose exposure: < 6 mg/day | • 3.8 ± 3.4 years (up to 16 years) | • Infection |
| • Non-matched | • Chronic medium dose exposure: 6–12 mg/day | • Gastrointestinal | |||
| • Mean age at index date: 57.6 ± 16.3 years | • Chronic high dose exposure: > 12 mg/day of prednisolone equivalent | • Bone/muscle | |||
| • Cardiovascular | |||||
| • Metabolic | |||||
| • Psychiatric | |||||
| • Ocular | |||||
| Zazzali et al. (2015)77 | Health insurance claims database (2008–2009), US | • Asthma (≥ 18 years old): ≥ 2 medical claims with asthma and ≥ 2 asthma medication fillings | • No exposure: no OCS supply during the year | • 2 years | • Osteoporosis |
| • Matched by age, sex and geographic region | • High dose exposure: ≥ 30 days of OCS supply in a year, regardless of cumulative dose | • Fracture | |||
| • Mean age at index date: 54.4 ± 12.7 years | • Pneumonia | ||||
| • Opportunistic infection | |||||
| • Hypertension | |||||
| • DM | |||||
| • Cataract | |||||
| • Obesity | |||||
| Dalal et al. (2016)56 | Large administrative claims databases (2003–2014 and 2006–2013; Truven Health MarketScan Research), US | • Asthma (≥ 12 years old): ≥ 2 administrative claims associated with an asthma diagnosis | • No exposure | • No exposure group: 1.1 ± 0.9 years | • Infection |
| • Propensity score matched (based on demographic and clinical co-variates) | • Chronic low dose exposure: < 5 mg/day | • Chronic SCS user group: 2.0 ± 1.9 years | • Bone/muscle | ||
| • Mean age at index date: 62.4 ± 15.2 years | • Chronic medium dose exposure: ≥ 5–10 mg/day | • Skin disease | |||
| • Chronic high dose exposure: > 10 mg/day (of prednisolone equivalent of ≥ 6 months' duration) | • Gastrointestinal (not in low dose group) | ||||
| • Cardiovascular (not in low dose group) | |||||
| • Metabolic (not in low dose group) | |||||
| • Psychiatric (not in low dose group) | |||||
| • Ocular (not in low dose group) | |||||
| Sweeney et al. (2016)58 | Primary care database (OPCRD), UK | • Asthma (≥ 12 years old): ≥ 2 years of continuous medical records of asthma | • No exposure (non-asthmatic control) | • Cross-sectional analysis of database information over 2 years | • Type 2 DM |
| • Severe asthma: step 5 GINA asthma treatment and ≥ 4 OCS prescriptions in each of two consecutive study years | • Mild/moderate asthma: a cumulative OCS dose over the 2 years: median 250 mg (IQR, 150–420 mg) | • Obesity | |||
| • Matched by age and sex | • Severe asthma: a cumulative OCS dose: 3,920 mg (2,395–6,500 mg) | • Osteopenia | |||
| • Mean age: 58 ± 17 years | • Osteoporosis | ||||
| • Fracture | |||||
| • Dyspeptic | |||||
| • Cataract | |||||
| • Cardiovascular | |||||
| • Hypertension | |||||
| • Psychiatric | |||||
| • Sleep disorder | |||||
| • Chronic kidney disease | |||||
| BTS Difficult Asthma Registry (2013), UK | • Severe asthma: diagnosed by specialists | • Severe non-OCS-dependent asthma: not requiring maintenance OCS but requirement for frequent OCS rescue | • Cross-sectional | • Type 2 DM | |
| • Mean age: 50 ± 14.5 years (2.1 years older in severe OCS-dependent asthma group) | • Severe OCS-dependent asthma: requiring daily OCS to maintain asthma control | • Hypertension | |||
| • Hypercholesterolemia | |||||
| • Obesity | |||||
| • Obstructive sleep apnoea | |||||
| • Dyspeptic | |||||
| • Psychiatric | |||||
| Lefebvre et al. (2017)78 | Health insurance claims database (1997–2013: Medicaid), US | • Asthma (≥ 12 years old): ≥ 2 administrative claims associated with an asthma diagnosis | • No exposure | • No exposure group: 2.1 ± 1.6 years | • Gastrointestinal |
| • Non-matched | • Chronic low dose exposure: < 6 mg/day | • Chronic SCS exposure group: 3.8 ± 3.4 years (up to 15 years) | • Infection | ||
| • Mean age at index date: 57.6 ± 16.3 years (for chronic SCS user) and 27.4 ± 17.7 years (for non-user) | • Chronic medium dose exposure: ≥ 6–12 mg/day | • Psychiatric | |||
| • Chronic high dose exposure: > 12 mg/day (of prednisolone equivalent of ≥ 6 months' duration) | • Ocular | ||||
| • Haemato/oncologic | |||||
| • Bone/muscle (not in low dose group) | |||||
| • Cardiovascular (not in low dose group) | |||||
| • Metabolic (not in low dose group) | |||||
| Barry et al. (2018)59 | Primary care database (OPCRD), UK | • Asthma (≥ 12 years old): ≥ 2 years of continuous medical records of asthma | • No exposure (non-asthmatic control) | • Cross-sectional analysis of database information over 2 years | • Overall risk of SCS-related comorbidities was more frequent in younger patients (≤ 45 years old) |
| • Severe asthma: step 5 GINA asthma treatment and ≥ 4 OCS prescriptions in each of two consecutive study years (same population and definitions as the study by Sweeney 201658) | • Mild/moderate asthma with a cumulative OCS dose over 2 years: median 250 mg (IQR, 150–420 mg) | • Risk of fracture was more frequent in older patients (> 70 years old) | |||
| • Matched by age and sex | • Severe asthma with a cumulative OCS dose: 3,920 mg (2,395–6,500 mg) | ||||
| Bloechliger et al. (2018)60 | Primary care database (2000–2015: Clinical Practice Research Datalink), UK | • Asthma (≥ 18 years old): aged 18 years or older with incident or prevalent asthma (defined as requiring at least GINA step 2 treatment) | • Never vs. ever exposure (≥ 1 OCS prescription recorded at any time before the index date) | • Up to 16 years | • Severe infection |
| • Matched by index date, follow-up duration, year of birth, sex, and duration of history in the database | • Timing of exposure (current, recent, or past users, when their last prescription was recorded < 180, 180–365, or > 365 days before the index date) | • Peptic ulcer | |||
| • Cumulative dose (< 500, 500–2,000, and > 2,000 mg) | • Affective disorders | ||||
| • Average daily dose (≤ 1, > 1–5, and > 5 mg) | • Cataract | ||||
| • Frequency of prescriptions (low use: on average 1 prescription/year; medium use: on average 2–3 prescriptions per year; and high use: on average ≥ 4 prescriptions per year) | • Herpes zoster | ||||
| • Cardiovascular events | |||||
| • Type 2 DM | |||||
| • Bone-related conditions | |||||
| Daugherty et al. (2018)61 | Primary care database (2004–2012: Clinical Practice Research Datalink), UK | • Severe asthma (≥ 18 years old): receiving GINA step 4/5 treatment during the pre-index phase | • Average cumulative SCS daily dose: 0, 0–2.5, 2.5–5, 5–7.5, and > 7.5 mg/day | • 3.83 ± 2.4 years (range: 0–8 years) | • Increased risk even at low dose exposure (0–2.5 mg/day vs. no exposure: DM, myocardial infarction and osteoporosis |
| • Mean age: 53.42 ± 18.1 years | |||||
| Price et al. (2018)62 | Primary care databases (1984–2017: OPCRD and Clinical Practice Research Datalink), UK | • Active asthma (≥ 18 years old; with at least two prescriptions for asthma medication in the period) without any record of SCS prescription before index date | • SCS arm (≥ 1 additional prescription for SCS within 18 months after first recorded SCS prescription) vs. non-SCS arm (no recorded parenteral or oral prescription ever) | • SCS arm: median 9.9 years (IQR 4.1–20.0) | • Osteoporosis and osteoporotic fracture |
| • Matched by sex, asthma diagnosis, index date, and the availability of Hospital Episode Statistics linkage | • Non-SCS arm: median 8.7 years (IQR, 3.7–18.2) | • Pneumonia | |||
| • Heart failure | |||||
| • Cardio-/cerebrovascular disease | |||||
| • Cataract | |||||
| • Myocardial infarction | |||||
| • Sleep apnoea | |||||
| • Renal impairment | |||||
| • Depression/anxiety | |||||
| • Cerebrovascular accident | |||||
| • Type 2 DM | |||||
| • Weight gain | |||||
| Sullivan et al. (2018)57 | Health insurance claims database (2000–2014: MarketScan), US | • Asthma (≥ 18 years old): 1) a diagnosis in at least 2 outpatient claims with primary or secondary diagnoses of asthma at least 1 of which must have been during the baseline period; or 2) at least 1 ED or hospitalization claim with a primary diagnosis of asthma during the baseline period | • No OCS exposure | • Range: 2–10 years | • High-level exposure: osteoporosis, hypertension, obesity, type 2 DM, cataract, gastrointestinal ulcers/bleeds, fracture |
| • Propensity score matched (based on age, sex, number of asthma-related ED visits, number of asthma-related inpatient visits, short-acting β agonist use and comorbidity burden) | • Lower level of exposure: 1 to 3 current OCS prescriptions in the current year (or in the past year) | ||||
| • Mean age: 38 years | • Higher level of exposure: 4 or more prescriptions for OCS drugs in the current year (or in the past year) |
SCS, systemic corticosteroid; OCS, oral corticosteroid; DM, diabetes mellitus; OPCRD, Optimum Patient Care Research Database; GINA, Global Initiative for Asthma; IQR, interquartile range; BTS, British Thoracic Society.
*Medical condition for which a significantly increased risk is reported and/or dose response (odds ratio > 1 with statistical significance).