Clinical, economic, and societal burden of cystic fibrosis and the impact of the CFTR modulator, lumacaftor/ivacaftor: an assessment using linked registry data in Sweden

Figures & data

Table 1. Demographics and clinical characteristics of people with CF^a in 2019 (n = 743).

Characteristic	People with CF in 2019 n (%)
Sex
Female	346 (47)
Male	397 (53)
	Mean (SD)
Age, years	25·8 (16·1)
ppFEV1^b	80·3 (23·2)
BMI^b	22·8 (3·7)
BMI z-score^b	−0·35 (1·03)
PEx event, No.^c	0·95 (1·64)
Dispensed oral antibiotics, No.	6·3 (6·1)
Supply of oral antibiotics, days	151·5 (178·7)
People with CF and ≥1 CF-related dispensation in 2019 (n%)
Antibiotics (any formulation)	690 (93)
Adrenergic inhalators/bronchodilators	659 (89)
Pancreatic enzymes	602 (81)
Antidiabetics	158 (21)

Abbreviations. BMI, body mass index; CF, cystic fibrosis; PEx, pulmonary exacerbation; ppFEV₁, percent predicted forced expiratory volume per second; SD, standard deviation.

^a The non-CF general population is not included here because most measures were only available for the CF population; because age and sex were matched, those values were the same.

^b Only people with a measurement were included: ppFEV₁: n = 625, BMI: n = 324, BMI z-score: n = 292. BMI was calculated in people aged ≥18 years, and BMI z-score was calculated in children aged <18 years.

^c Based on intravenous antibiotics in Prescription Drug Registry (extemporaneous preparation + specified as intravenous).

Figure 1. Mean HCRU in 2019 for people with CF compared with the general population. (a) Number of outpatient specialist visits. (b) Number of hospitalizations. (c) Number of hospitalization days. (d) Number of CF-related dispensations. (e) Number of days’ work absence. (f) Number of VAB leave days. Values graphed are means. Deltas (Δ) indicate differences in the means, which are followed by the 95% confidence intervals. The number of people with CF included in the analyses were: 743 of any age, 270 children aged <18 years, 473 adults aged ≥18 years, 18 children aged <2 years, 159 children aged 2 to <12 years, and 93 children aged 12 to <18 years. The number of people in the control groups were: 7406 of any age, 2700 children aged <18 years, 4706 adults aged ≥18 years, 180 children aged <2 years, 1590 children aged 2 to <12 years, and 930 children aged 12 to <18 years. CF-related dispensations included adrenergic inhalators/bronchodilators, antibiotics, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antifungals, antihistamines, anti-inflammatory agents, anxiolytics, corticosteroids, expectorant drugs, gastroesophageal reflux disease medications, growth hormones, opioids, osteoporosis drugs, oxygen, pancreatic enzymes, transplant immunosuppressants, and vitamins. CF, cystic fibrosis; HRCU, healthcare resource utilization; VAB, care of sick child (vård av barn).

Table 2. Comparison of total costs (€ 2020) in people with CF and controls in 2019^a.

	People with CF (n = 743)	Controls (n = 7406)	Difference (95% CI)^b
Direct costs € 2020; Mean (SD)
Outpatient specialist visits	4544 (4631)	381 (1023)	4163 (4034, 4291)
aged <18 years	4341 (1959)	328 (915)	4014 (3882, 4146)
aged ≥18 years	4660 (5611)	412 (1079)	4248 (4060, 4435)
Hospitalizations	4157 (14,453)	342 (2226)	3814 (3448, 4180)
aged <18 years	2403 (6371)	171 (1327)	2232 (1945, 2520)
aged ≥18 years	5158 (17,392)	441 (2600)	4717 (4168, 5266)
CF-related dispensations^c	12,524 (16,646)	64 (555)	12,460(12,079, 12,841)
All dispensations^d	14,532 (18,181)	247 (4245)	14,285(13,770, 14,799)
Total direct costs	23,233 (26,690)	970 (5,407)	22,263 (21,540, 22,983)
Indirect costs € 2020; Mean (SD)^e
Work absence	9147 (17,640)	1783 (8361)	7364 (6641, 8087)
aged ≥18 years	14,369 (20,346)	2806 (10,351)	11,563 (10,463, 12,662)
VAB leave	482 (1545)	155 (712)	327 (265, 389)
aged <2 years	3211 (5989)	442 (781)	2768 (1835, 3702)
aged 2 to <12 years	1359 (1812)	573 (1342)	786 (559, 1013)
aged 12 to <18 years	650 (1199)	43 (245)	607 (515, 698)
aged <18 years	1325 (2338)	423 (1128)	902 (742, 1063)
Total indirect costs	9629 (17,456)	1938 (8359)	7691 (6970, 8412)

Abbreviations. CF, cystic fibrosis; CFTRm, CF transmembrane conductance regulator modulator; LUM/IVA, lumacaftor/ivacaftor; SD, standard deviation; VAB, care of sick child (vård av barn).

^a The number of children with CF and in the control group (respectively) included in the analyses were: aged <18 years: 270 and 2700; aged <2 years: 18 and 180; aged 2 to <12 years: 159 and 1590; aged 12 to <18 years: 93 and 930. A total of 473 adults (aged ≥18 years) with CF and 4706 controls were included in the analyses.

^b Expressed as the difference of the means.

^c Included adrenergic inhalators/bronchodilators, antibiotics, anti-coagulants, anticonvulsants, antidepressants, antidiabetics, antifungals, antihistamines, anti-inflammatory agents, anxiolytics, corticosteroids, expectorant drugs, gastroesophageal reflux disease medications, growth hormones, opioids, osteoporosis drugs, oxygen, pancreatic enzymes, transplant immunosuppressants, vitamins.

^d Except CFTRm.

^e Indirect costs associated with work absence and VAB leave days were calculated by multiplying the number of days on an individual level with an assumed daily value of lost productivity. In accordance with the human capital approach, this value was assumed to be equal to the mean cost of labor (i.e. wages) in Sweden plus payroll taxes (based on census statistics from Statistics Sweden). Wages were sex-adjusted.

Table 3. Impact of treating with LUM/IVA on clinical outcomes^a.

	No. of people	Preindex; Mean (SD)	Postindex; Mean (SD)	Change (95% CI)^b
N treated with LUM/IVA	100
ppFEV1	89	73·7 (23·7)	77·5 (24·3)	3·8 (1·1, 6·6)
BMI^c	51	21·5 (2·2)	22·2 (2·4)	0·7 (0·5, 1·0)
BMI z-score^c	38	−0·4 (0·8)	−0·2 (0·9)	0·3 (0·1, 0·4)
Sweat chloride test, mmol/L	40	104·2 (11·0)	83·3 (13·2)	−20·9 (−25·1, −16·6)
Lung clearance index	28	10·0 (2·4)	9·1 (2·0)	−1·0 (−1·6, −0·3)
CFQ-R14–respiratory score^d	40	69·0 (15·1)	75·7 (16·9)	6·7 (1·1, 12·3)
PEx event, n	100	1·7 (2·1)	1·2 (1·8)	−0·5 (−0·8, −0·2)

Abbreviations. BMI, body mass index; CFQ-R, Cystic Fibrosis Questionnaire Revised; LUM/IVA, lumacaftor/ivacaftor; PEx, pulmonary exacerbations; ppFEV₁, percent predicted forced expiratory volume per second.

^a Values are expressed as means (standard deviation) unless otherwise indicated. Overall, data from 100 people were analyzed; however, only people with ≥1 measurement reported in both pre-index and post-index periods were included. Of the 100 people analyzed, 56% were male and the mean age at index was 24.1 years.

^b Change is expressed as the difference of the means (95% confidence interval).

^c BMI was calculated in people aged ≥18 years; and BMI z-score was calculated in children aged <18 years.

^d This measure includes only people aged ≥14 years.

Table 4. Impact of treatment with LUM/IVA on resource use and costs^a.

	Preindex period	Postindex period	Change (95% CI)^b
Resource use, Mean (SD)
Resource
Outpatient specialist visits	12·13 (6·5)	13·22 (6·5)	1·09 (0·01, 2·17)
Hospitalizations	0·52 (1·1)	0·35 (0·8)	−0·17 (−0·40, 0·06)
Hospital days	2·48 (6·0)	1·61 (5·5)	−0·87 (−2·25, 0·51)
CF-related dispensations^c	37·64 (17·1)	34·41 (19·9)	−3·23 (−5·23, −1·23)
Dispensed antibiotics	14·99 (9·2)	12·11 (9·6)	−2·88 (−4·04, −1·72)
Dispensed oral antibiotics, n	8·04 (5·8)	6·57 (5·2)	−1·47 (−2·27, −0·67)
Supply of oral antibiotics, days	253·48 (253·8)	208·26 (232·0)	−45·22 (−77·17, −13·27)
Work absence days	44·80 (91·5)	50·30 (98·8)	5·50 (−3·64, 14·64)
aged ≥18 years	74·66 (108·6)	83·83 (116·2)	9·17 (−6·17, 24·51)
VAB leave days	3·73 (8·2)	1·57 (4·1)	−2·16 (−3·26, −1·05)
aged <18 years	9·32 (10·8)	3·93 (5·8)	−5·39 (−7·90, −2·89)
Costs € 2020; Mean (SD)
Direct costs
Outpatient specialist visits	4408 (2421)	4867 (2588)	459 (32, 886)
Hospitalizations	2217 (4415)	2868 (13788)	651 (−2049, 3351)
All dispensations^d	21,496 (20,474)	18,055 (16,996)	−3442 (−6425, −459)
Indirect costs^e
Work absence	6681 (13,780)	7488 (14782)	808 (−494, 2109)
aged ≥18 years	11,134 (16,377)	12,480 (17,416)	1346 (−838, 3530)
VAB leave	547 (1210)	232 (606)	−316 (−477, −154)
aged <18 years	1368 (1600)	580 (851)	−789 (−1155, −423)

Abbreviations. CF, cystic fibrosis; CFTRm, CF transmembrane conductance regulator modulator; LUM/IVA, lumacaftor/ivacaftor; SD, standard deviation; VAB, care of sick child (vård av barn).

^a Overall, data from 100 people were analyzed; 60 were aged ≥18 years, and 40 were aged <18 years.

^b Change is expressed as the difference of the means.

^c Included adrenergic inhalators/bronchodilators, antibiotics, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antifungals, antihistamines, anti-inflammatory agents, anxiolytics, corticosteroids, expectorant drugs, gastroesophageal reflux disease medications, growth hormones, opioids, osteoporosis drugs, oxygen, pancreatic enzymes, transplant immunosuppressants, vitamins.

^d Except CFTRm.

^e Indirect costs associated with sick leave/disability pension and VAB leave days were calculated by multiplying the number of net days on an individual level with an assumed value of lost productivity. In accordance with the human capital approach, this value was assumed to be equal to the mean cost of labor (i.e. wages) in Sweden plus payroll taxes (based on census statistics from Statistics Sweden). Wages were sex adjusted.

Data sharing statement

Each registry holder collects and manages its own data and maintains processes for researchers to request data. Restrictions apply to the sharing of these data, which were accessed for the purposes of the study based on an ethics approval and individual agreements with each respective registry holder.