Cost-effectiveness of using an extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG in managing IgE-mediated cow’s milk protein allergy in the UK

Figures & data

Figure 1. Diagrammatic representation of the Markov model.

Figure 2. Time-series forecasting of the clinical outcomes from the RCT¹². (a) Manifestation of urticaria; (b) manifestation of eczema; (c) manifestation of asthma; (d) manifestation of rhinoconjunctivitis; (e) manifestation of symptomatic patients; (f) acquisition of tolerance to cow’s milk.

Table 1. Annual transition probabilities in the Markov model.

Time (years)	Formula	Probability of moving into each state at the end of a 12 month period
		CMPA/urticaria	Eczema	Asthma	Rhinoconjunctivitis	Symptom free
0	eHCF plus LGG	1.00	0.00	0.00	0.00	0.00
1	eHCF plus LGG	0.04	0.14	0.06	0.05	0.71
2	eHCF plus LGG	0.02	0.00	0.02	0.02	0.94
3	eHCF plus LGG	0.02	0.01	0.01	0.01	0.95
4	eHCF plus LGG	0.01	0.02	0.00	0.00	0.97
5	eHCF plus LGG	0.00	0.03	0.00	0.00	0.97
0	eHCF alone	1.00	0.00	0.00	0.00	0.00
1	eHCF alone	0.19	0.18	0.02	0.05	0.56
2	eHCF alone	0.00	0.03	0.08	0.03	0.86
3	eHCF alone	0.02	0.06	0.08	0.06	0.77
4	eHCF alone	0.00	0.07	0.09	0.07	0.77
5	eHCF alone	0.00	0.08	0.09	0.07	0.76

Table 2. Estimates of resource use incorporated into the model.

	Mean amount of resource use per patient in
	Year 1	Year 2	Year 3	Year 4	Year 5
Management of CMPA/urticaria
GP visits (mean per patient)	8.00	3.00	2.00	2.00	2.00
General paediatrician visits (mean per patient)	1.00	1.00	1.00	0.50	0.50
Paediatric allergist visits (mean per patient)	0.84	0.84	0.84	0.42	0.42
Dietitian visits (mean per patient)	2.80	1.64	1.64	1.64	1.64
Accident & emergency attendances (mean per patient)	0.30	0.30	0.00	0.00	0.00
Hospital admissions (mean per patient)	0.08	0.05	0.03	0.02	0.02
Percentage referred to a general paediatrician	50	0	0	0	0
Percentage referred to a paediatric allergist	40	0	0	0	0
Percentage referred to a dietitian	90	0	0	0	0
Percentage prescribed H2 antagonists or proton pump inhibitors	28	0	0	0	0
Percentage prescribed emollients	85	0	0	0	0
Percentage prescribed systemic corticosteroids	3	3	3	3	3
Percentage prescribed topical corticosteroids	50	50	50	50	50
Percentage prescribed antihistamines	60	60	60	60	60
Management of eczema
GP visits (mean per patient)	4.00	3.00	3.00	3.00	3.00
General paediatrician visits (mean per patient)	0.90	0.90	0.90	0.45	0.45
Paediatric dermatologist visits (mean per patient)	0.03	0.06	0.06	0.03	0.03
Accident & emergency attendances (mean per patient)	0.13	0.13	0.13	0.13	0.13
Hospital admissions (mean per patient)	0.03	0.03	0.03	0.03	0.03
Percentage referred to a general paediatrician	45	0	0	0	0
Percentage referred to a dermatologist	3	0	0	0	0
Percentage prescribed emollients	100	100	100	100	100
Percentage prescribed topical corticosteroids	70	70	70	70	70
Percentage prescribed antihistamines	50	50	50	50	50
Management of asthma
GP visits (mean per patient)	7.00	6.00	5.00	5.00	4.00
General paediatrician visits (mean per patient)	2.00	0.90	0.90	0.90	0.90
Accident & emergency attendances (mean per patient)	0.20	0.20	0.20	0.20	0.20
Hospital admissions (mean per patient)	0.40	0.40	0.40	0.40	0.40
Percentage referred to a general paediatrician	65	0	0	0	0
Percentage prescribed systemic corticosteroids	40	40	40	40	40
Percentage prescribed Ventolin/beta agonists	100	100	100	100	100
Percentage prescribed inhaled corticosteroids	55	55	55	55	55
Management of rhinoconjunctivitis
GP visits (mean per patient)	2.00	2.00	2.00	2.00	2.00
General paediatrician visits (mean per patient)	0.10	0.00	0.00	0.00	0.00
Accident & emergency attendances (mean per patient)	0.03	0.00	0.00	0.00	0.00
Percentage referred to a general paediatrician	5	0	0	0	0
Percentage prescribed antihistamines	80	80	80	80	80

Table 3. Unit resource costs at 2016/17 prices.

Resource	Unit cost
GP clinic visit	£66.90
GP home visit	£80.67
Initial visit general paediatrician	£236.00
Follow-up visit general paediatrician	£189.00
Initial visit paediatric allergist	£244.00
Follow-up visit paediatric allergist	£186.00
Initial visit paediatric dermatologist	£114.00
Follow-up visit paediatric dermatologist	£101.00
Initial visit dietitian	£91.00
Follow-up visit dietitian	£69.00
Accident & emergency attendance	£149.78
Hospital admission	£1434.00
Weekly prescription for proton pump inhibitors	£58.12
Monthly prescription for emollients	£5.01
Weekly prescription for systemic corticosteroids	£18.08
Monthly prescription for topical corticosteroids	£5.96
Monthly prescription for antihistamines	£5.41
Monthly prescription for inhaled corticosteroids	£10.90
Monthly prescription of salbutamol 100 mcg/dose	£1.50
eHCF (per 400 g can)	£11.21
eHCF plus LGG (per 400 g can)	£11.21

Table 4. Expected clinical outcomes at three and five years from the start of treatment.

	eHCF alone	eHCF plus LGG
Probability of not experiencing any allergic symptoms
3 years	0.77	0.95
5 years	0.76	0.97
Probability of acquiring tolerance to cow’s milk
3 years	0.55	0.81
5 years	0.66	0.94

Table 5. Mean amount of resource use per patient over five years from the start of treatment.

	eHCF alone	eHCF plus LGG
GP visits	20.22	16.70
Specialist visits	5.12	3.74
Dietitian visits	5.73	4.40
Hospital admissions	0.26	0.16
Accident & emergency attendances	0.59	0.48
Prescriptions for H2 antagonists/proton pump inhibitors	1.40	1.40
Prescriptions for emollients	21.40	14.90
Prescriptions for systemic corticosteroids	0.42	0.17
Prescriptions for topical corticosteroids	4.75	3.30
Prescriptions for antihistamines	4.29	2.82
Prescriptions for salbutamol 100 mcg/dose	1.68	0.55
Prescriptions for inhaled corticosteroids	1.84	0.61
Clinical nutrition (400 g cans)	182.40	166.96

Table 6. Mean cost (at 2016/17 prices) per patient over five years from the start of treatment (percentage of total cost in parentheses).

	eHCF alone		eHCF plus LGG
GP visits	£1102.73	(21)	£892.08	(21)
Specialist visits	£966.81	(19)	£729.71	(17)
Dietitian visits	£399.53	(8)	£316.10	(7)
Hospital admissions	£355.25	(7)	£223.01	(5)
Accident & emergency attendances	£86.03	(2)	£70.79	(2)
Prescribed drugs	£205.42	(4)	£143.99	(3)
Clinical nutrition	£2020.22	(39)	£1853.19	(44)
Total	£5135.99	(100)	£4228.87	(100)

Table 7. Cost-effectiveness analyses at three and five years from the start of treatment.

	NHS cost per patient	Probability of tolerance to cow’s milk	Probability of being symptom free	Incremental cost for each additional infant who was:
				Tolerant to cow’s milk	Symptom free
At 3 years
eHCF plus LGG	£4091	0.81	0.95
eHCF alone	£4588	0.55	0.77
Difference	−£497	0.26	0.18
Cost-effectiveness				−£1922	−£2754
At 5 years
eHCF plus LGG	£4229	0.94	0.97
eHCF alone	£5136	0.66	0.76
Difference	−£907	0.28	0.21
Cost-effectiveness				−£3240	−£4320

Figure 3. Scatterplot of the incremental cost-effectiveness of eHCF plus LGG compared to eHCF alone (10,000 iterations of the model); (a) Measure of effectiveness is probability of being symptom-free; (b) measure of effectiveness is probability of acquiring tolerance to cow’s milk.

Table 8. Sensitivity analyses.

Scenario	Incremental cost for each additional infant who was:
	Tolerant to cow’s milk	Symptom free
The probability of allergic manifestation and developing tolerance to cow’s milk in years 4 and 5 remained unchanged from those at year 3	−£3417	−£4897
The probability of allergic manifestation in years 4 and 5 remained unchanged from those at year 3 and the probability of developing tolerance to cow’s milk in years 4 and 5 remains as predicted	−£3196	−£4956
Reduce the amount of resource use attributable to managing the allergic manifestations of eczema, rhinoconjunctivitis and asthma by 25%	−£2283	−£3844
Increase the amount of resource use attributable to managing the allergic manifestations of eczema, rhinoconjunctivitis and asthma by 25%	−£3330	−£4440
Decrease the amount of resource use attributable to managing CMPA and the allergic manifestations of eczema, rhinoconjunctivitis and asthma by 25%	−£2313	−£3084
Increase the amount of resource use attributable to managing CMPA and the allergic manifestations of eczema, rhinoconjunctivitis and asthma by 25%	−£3890	−£5200
Decrease the amount of resource use attributable to managing CMPA and the allergic manifestations of eczema, rhinoconjunctivitis and asthma by 25% but assume all patients were symptom free and tolerant to cow’s milk by year 5	−£14,874	−£11,117
Increase the amount of resource use attributable to managing CMPA and the allergic manifestations of eczema, rhinoconjunctivitis and asthma by 25% but assume all patients were symptom free and tolerant to cow’s milk by year 5	−£23,638	−£19,737
Formula is no longer prescribed once an infant reaches 18 months of age	−£2941	−£3922
Change the cost of the comparator eHCF to £9.20 per 400 g can	−£1722	−£2296

Berni Canani R, Di Costanzo M, Bedogni G, et al. Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow’s milk allergy: 3-year randomized controlled trial. J Allergy Clin Immunol. 2017;139:1906–1913.e1904.

 PubMed Web of Science ®Google Scholar