Table 2.
Frequency of Long-Term Use of OCS and SCS for Patients with Asthma, Categorized by Disease Severity
| Source | N | Long-Term OCS/SCS Definition | OCS/SCS Use at Follow-Up/Postindex, % (n/N) | OCS/SCS Use at Baseline/Preindex, % (n/N) |
|---|---|---|---|---|
| Any degree of asthma severity | ||||
| Allen-Ramey et al., 2013 (30) (U.S.) | 21,199 | An order quantity ≥30 with one or more refills | OCS | — |
| 8.9 (1,883/21,199) | ||||
| Arellano et al., 2011 (79) (U.S.) | 6–18 yr: 659,169 | Continuous OCS use >15 d | Addition of long-term OCS in first year in Tx-naive pts initiating Tx with: | — |
| 6–11 yr: 348,991 | SABA (n = 309,947): 22.8% | |||
| Tx-naive (6–18 yr): 595,619 | ICS (n = 16,783): 18.5% | |||
| ICS/LABA (n = 13,980): 15.1% | ||||
| Bottero et al., 2014 (125) (Italy) | 159 | Continuous or near continuous (≥50% of yr) oral prednisone use | OCS | — |
| 9.4 (15/159) | ||||
|
HLA-DRB4 positive: 16.7 (10/60) | ||||
|
HLA-DRB4 negative: 5.1 (5/99) | ||||
| Broder et al., 2010 (56) (U.S.) | 18,343 (uncontrolled asthma) | Total supply of ≥60 d in a 6-mo period |
— | OCS Preindex (EPR3 step 6): 0.6 (105/18,343) |
| Covvey et al., 2013 (47) (UK) | 12,319 | >14-d supply with no titration schedule (BTS/SIGN step 5) | 1.2 (149/12,319) | — |
| Dalal et al., 2016 (103) (U.S.) | 603,147; SCS users: 12,697 Nonusers: 590,450 |
SCS user: ≥6 mo of continuous long-term SCS use Nonuser: never exposed to SCS |
— | Long-term SCS use (overall pop): 2.1 (12,697/603,147) |
| Dodd and Mazurek, 2018* (59) (U.S.) | 14,915 | Controller therapy | OCS | — |
| % (95% CI) | ||||
| WRA: 5.5 (3.8–7.3) | ||||
| Possible WRA: 3.0 (1.8–4.2) | ||||
| Non-WRA: 2.5 (1.7–3.4) | ||||
| Fardet 2011 (57) (UK) | 4,518,753 (total) 167,886 (long-term OCS) |
Tx lasting ≥3 mo | OCS | — |
| Prevalence, % (95% CI): 1.3 (1.1–1.4)† | ||||
| Ferguson et al., 2014‡ (60) (U.S.) | 812 | Long-term OCS | OCS | — |
| 9 (70/812) | ||||
| Hasegawa et al., 2012‡§ (61) (Japan) | 1998: 3,347 | Controller medication | OCS | — |
| 1998: 18.8 | ||||
| 2000: 3,069 | 2000: 12.3 | |||
| 2002: 2,593 | 2002: 10.4 | |||
| 2004: 2,865 | 2004: 7.4 | |||
| 2006: 3,066 | 2006: 7.8 | |||
| 2008: 3,146 | 2008: 5.2 | |||
| P < 0.001 over study | ||||
| Korn 2013§|| (55) (Germany) | 280 | Daily OCS maintenance | OCS | — |
| 26.8 (75/280) | ||||
| Vitamin D concentrations | ||||
| 25(OH)D <30 ng/ml (insufficiency): | ||||
| 30.9 (58/188) | ||||
| 25(OH)D ≥30 ng/ml: | ||||
| 18.5 (17/92) | ||||
| P = 0.031 | ||||
| Lee et al., 2013 (98) (South Korea) | TB cases: 4,136 Matched control subjects: 20,538¶ | OCS user: cumulative dosage ≥1,680 mg of hydrocortisone equivalents during 1 yr before index date | — | OCS |
| Asthma pts | ||||
| TB cases: 11.2 (54/484) | ||||
| Control subjects: 4.8 (117/2,420) | ||||
| Lefebvre et al., 2017** (106) (U.S.) | SCS users: 3,628 Nonusers: 26,987 |
Daily doses ≥5 mg of prednisone equivalent with no gap of ≥14 d between 2 SCS claims | — | Overall population: 11.9 (3,628/30,615) |
| Luskin et al., 2016†† (49) (U.S.) | 3,604 (high OCS use) | High OCS use: pts who had a ≥30-d supply of OCS in each study year | OCS | — |
| 5.3 (3,604/67,860) | ||||
| Papaioannou et al., 2016 (62) (Greece) | 171 | Regular/continuous SCS | OCS | — |
| 20.5 (35/171) | ||||
| Price et al., 2015 (35) (UK) | 2,042‡‡ | BTS step 5 | — | OCS |
| 0.5 (10/2,042) | ||||
| Price et al., 2016 (58) (UK) | 130,547 | BTS step 5 | — | OCS |
| 0.8 (1,080/130,547) | ||||
| Reddy et al., 2011§§ (63) (U.S.) | (257‖‖) | Regular OCS | OCS | OCS |
| 5.8 (15/257) | 10.9 (28/257) | |||
| P = 0.055 vs. baseline | — | |||
| Sato et al., 2017 (64) (Japan) | 114 | Regular use of OCS | OCS | — |
| 4 (5/114) | ||||
| Shigemura et al., 2012‡ (65) (Japan) | 126 | Regular OCS | — | OCS |
| Baseline: 15.4 (18/117) | ||||
| Tattersall et al., 2015|| (66) (U.S.) | 667; Intermittent: 511 Persistent: 156 |
Controller medication | — | OCS |
| Overall: 4.8 (32/667) | ||||
| Persistent: 20.5 (32/156) | ||||
| Intermittent: NA | ||||
| Zeiger et al., 2017 (94) (U.S.) | 9,546 | Long-term OCS: Average daily dosage ≥2.5 mg in 2010 Short-term OCS: average daily dosage <2.5 mg or no OCS in 2010 |
Long-term OCS: 8.2 (782/9,546) | — |
| Long-term OCS: 782 Short-term OCS: 8,764 | ||||
| GINA step 2 or greater treatment | ||||
| Bengtson et al., 2017 (4) (U.S.) | Escalation: 5,044 Unchanged: 21,967 |
≥90 consecutive days of OCS coverage | Unchanged: 0.2 (52/21,967) Escalation: |
— |
| Before: 0.1 (6/5,044) After: 0.1 (7/5,044) | ||||
| Hawcutt et al., 2015¶¶ (126) (UK) | 525 | Regular maintenance | 10.8 (47/435) | — |
| Barry 2017†† (96) (UK) | 7,195; Severe: 808 Mild/moderate: 3,975 Nonasthma: 2,412 |
Severe asthma: regular OCS use*** | Severe: 100 (808/808) Mild/moderate: 25 (995/3,975) Nonasthma: 0 (0/2,412) |
— |
| Broder 2017 (92) (U.S.) | 3,355 | High OCS users: ≥1 OCS fill with ≥30 d of supply or ≥6 bursts of OCS | High OCS use: 15.4 (517/3,355) |
— |
| Chipps et al., 2017‡ (33) (U.S.) | 341††† | Long-term SCS | 11.2 (37/331) | — |
| Daugherty et al., 2017 (104) (UK) | 60,418; SCS nonuser: 24,994 SCS user: 35,444 |
SCS user: SCS use at baseline and observation periods‡‡‡ |
58.6 (35,444/60,418) | 25.6 (15,490/60,418) |
| SCS nonuser: no SCS use at baseline or observation periods‡‡‡ | (SCS use during baseline and observation periods) | — | ||
| Denlinger et al., 2017‡ (42) (U.S.) | 709 | Daily OCS | 11.0 (78/709) | — |
| Gibeon et al., 2015|| (43) (UK) | 346 | Maintenance OCS | 42.6 (123/289) | 41.2 (119/289) |
| Lefebvre et al., 2015** (105) (U.S.) | 3,628; SCS exposure (mg/d): Low (≤6): 368 Medium (>6–12): 1,630 High (>12): 1,630 |
Daily SCS dosage ≥5 mg of prednisone equivalent with no gap of ≥14 d between two SCS claims | At index date§§§ | — |
| Low SCS: 10 (368/3,628) Medium SCS: 45 (1,630/3,628) High SCS: 45 (1,630/3,628) | ||||
| Maio et al., 2017|| (46) (Italy) | 493 | Long-term OCS use | 16.0 (78/488) | — |
| Moore 2011|| (119) (U.S.) | 339; Nonsevere: 196 Severe: 102 Very severe: 41 |
OCS ≥20 mg/d for ≥50% of year | — | Baseline: % |
| Nonsevere: 1 (2/196) | ||||
| Severe: 21 (21/102) | ||||
| Very severe: 80 (33/41) | ||||
| P < 0.0001 | ||||
| O’Neill et al., 2015 (34) (UK) | 596; Severe: 516 Nonsevere: 80 |
Maintenance OCS | — | Overall: 34 (201/596) |
| Severe: 38 (196/516) | ||||
| Nonsevere: 5 (6/80) | ||||
| Phipatanakul et al., 2017|| (25) (U.S.) | 6–17 yr: 188; Nonsevere: 77 Severe: 111 |
≥3 mo with OCS use in past year | — | 6–17 yr |
| Nonsevere: 1.3 (1/77) | ||||
| Severe: 9.9 (11/111) P < 0.05 | ||||
| Adult (≥18 yr): 526; Nonsevere: 213 Severe: 313 |
Adult | |||
| Nonsevere: 0 (0/213) | ||||
| Severe: 22.4 (70/313) P < 0.01 | ||||
| Reddy et al., 2014§§ (67) (U.S.) | 228; Current (2003–2007): 65 Historic (1993–1997): 163 |
Daily OCS use | Current: 28 (11/41) Historic: 51 (28/55) P = 0.002 |
— |
| Rijssenbeek-Nouwens et al., 2012|| (127) (the Netherlands) | 137‖‖‖ | Daily OCS maintenance | Overall: 29.9 (41/137) | Overall: 51.1 (70/137) |
| HDM: 68 | HDM: 22 (15/68); P < 0.001 vs. baseline | HDM: 43 (29/68) | ||
| Non-HDM: 69 | Non-HDM: 38 (26/69); P < 0.001 vs. baseline | Non-HDM: 59 (41/69) | ||
| SEN: 92 | SEN: 29 (27/92); P < 0.001 vs. baseline | SEN: 49 (45/92) | ||
| Non-SEN: 45 | Non-SEN: 31 (14/45); P < 0.001 vs. baseline | Non-SEN: 56 (25/45) | ||
| Schleich et al., 2014‡ (128) (Belgium) | 350 | Daily maintenance SCS | 24 (84/350) | — |
| Shaw et al., 2015‡|| (75) (Europe) | 209; Severe nonsmoker: 311 Sever current/ex-smoker: 110 Mild/moderate: 88 |
Daily OCS | — | Severe all: 45.5 (181/398) |
| Severe nonsmoker: 45.8 (135/295) | ||||
| Severe ex-smoker: 44.7 (46/103) | ||||
| Mild/moderate: 0 (0/88) | ||||
| Sweeney et al., 2012 (76) (UK) | 349 | Maintenance OCS | 57 (199/349) | 42 (146/349) |
| Sweeney et al., 2016 (102) (UK) | 770¶¶¶ | Daily SCS | 57.1 (442/770) | — |
| Tay et al., 2017‡|| (129) (Singapore) | 423 | Maintenance OCS | — | 1.4 (6/423) |
| Severe: 4.1 (2/49) | ||||
| Nonsevere: 1.1 (4/374) | ||||
| Westerhof et al., 2016‡ (95) (the Netherlands) | 153; Current/ex-smoker: 83 Never-smoker: 70 |
Long-term OCS use >50% past yr | — | Current/ex-smoker: 28 (23/83) |
| Never-smoker: 29 (20/70) |
Definition of abbreviations: 25(OH)D = 25-hydroxyvitamin D; BTS = British Thoracic Society; CI = confidence interval; EPR = expert panel report; GINA = Global Initiative for Asthma; HCP = healthcare professional; HDM = house dust mite; ICS = inhaled corticosteroids; LABA = long-acting β2-agonists; NA = not applicable; OCS = oral corticosteroids; pts = patients; SABA = short-acting β2-agonists; SCS = systemic corticosteroids; SEN = sensitized; SIGN = Scottish Intercollegiate Guidelines Network; TB = tuberculosis; Tx = treatment; WRA = work-related asthma.
Studies used a retrospective cohort study design unless otherwise stated.
Patient survey.
Prevalence was determined by dividing the number of person-years with asthma receiving long-term OCS therapy by the total number of person-years with asthma.
Cross-sectional study.
Patient/HCP survey.
Prospective study.
Cases of TB identified after the treatment initiation date were matched with up to five control individuals without TB for age, sex, diagnosis of asthma or chronic obstructive pulmonary disease, and initiation date.
Longitudinal open cohort.
Retrospective matched cohort.
Patients who received tiotropium add-on therapy postindex (dry powder inhaler or soft mist inhaler).
Retrospective cross-sectional and historic cohort.
Patients with asthma who underwent bariatric surgery, consented to and had reached 1 yr of follow-up (n = 606), and returned for a follow-up survey (n = 257).
Prospective/retrospective cohort.
GINA Step 5 treatment and four or more OCS prescriptions per year for each of the two consecutive study years.
Data from TENOR (The Epidemiology and Natural History of Asthma. Outcomes and Treatment Regimens) II, a 10-year follow-up assessment of patients from TENOR I; age criteria provided for inclusion in TENOR I study.
Baseline period: 6 months before index date (date the patient was identified as having severe asthma [GINA Step 4/5]); observation period: follow-up after index date.
Index date was defined as the first day with a daily dosage of ≥5 mg of prednisone or equivalent after the first 6 months of long-term SCS use (baseline period).
High-altitude therapy for patients with severe asthma and without HDM sensitization (HDM and non-HDM groups) and patients with and without any allergic sensitization (sensitized and nonsensitized groups).
Patients with severe asthma at registry baseline assessment. Patients were divided into two groups: those who required daily SCS therapy to maintain asthma control and those who did not require maintenance SCS but required frequent rescue SCS courses.