Increasing economic burden of tyrosine kinase inhibitor treatment failure by line of therapy in chronic myeloid leukemia

Figures & data

Figure 1. Treatment episode example. The above is just an example of treatment episode identification at the patient level to illustrate a potential sequence of treatment. 1L = first line; 2L = second line; 3L = third line; CE = continuous health plan enrollment.

Figure 2. Study sample selection flow. 1L = first line; 2L = second line; 3L = third line; CML = chronic myeloid leukemia; TKI = tyrosine kinase inhibitor; LOT = line of therapy.

Table 1. Proportion failing treatment at specific timepoints among treatment episodes of TKI Initiation by LOT.

With continuous enrollment from index at the measured time point	3 months	6 months	1 year	2 years	3 years
	1L Treatment Episodes (N = 1759)
	(N = 1640)	(N = 1533)	(N = 1323)	(N = 733)	(N = 358)
No longer on index TKI	104 (6.3%)	348 (22.7%)	458 (34.6%)	364 (49.7%)	200 (55.9%)
	2L Treatment Episodes (N = 588)
	(N = 540)	(N = 508)	(N = 433)	(N = 198)	(N = 72)
No longer on index TKI	86 (15.9%)	151 (29.7%)	186 (43.0%)	114 (57.6%)	48 (66.7%)
	3L Treatment Episodes (N = 27)
	(N = 25)	(N = 21)	(N = 18)	(N = 6)	(N = 2)
No longer on index TKI	5 (20.0%)	10 (47.6%)	10 (55.6%)	N/A	N/A

Table 2. Baseline characteristics of the final sample with TKI treatment failure by line of therapy.

Characteristic	1L Failures	2L Failures	3L Failures
	(N = 518)	(N = 180)	(N = 8)
Pre-index
CCI score
Mean (SD)	2.6 (1.4)	2.5 (0.9)	2.6 (1.4)
Distribution, %
0–1	5.6	0.6	0
2	58.5	70.0	75.0
3	20.7	18.3	12.5
4+	15.3	11.1	12.5
Comorbidities, %
Anemia	31.1	34.4	87.5
Chronic pulmonary disease	7.9	5.6	12.5
Depression	7.9	9.4	12.5
Diabetes	18.3	11.7	0.0
Fluid electrolyte disorders	8.3	9.4	12.5
Hyperlipidemia	26.3	18.9	0.0
Hypertension	33.4	22.2	25.0
Peripheral vascular disease	4.1	1.7	0.0
Renal failure	7.3	1.7	0.0
Solid tumor	9.1	7.2	25.0
Valvular disease	4.8	6.1	0.0
CML severity, %^a
None or low	11.6	6.1	0.0
Moderate	69.1	85.0	87.5
High	19.3	8.9	12.5
Cancer complexity, %^b
None	51.7	51.7	37.5
Moderate	29.2	28.3	37.5
High	19.1	20.0	25.0
Pre-index total cost*
Mean (SD)	$13,462 (21,899)	$28,537 (24,711)	$80,699 (93,689)
Pre-index total (non-TKI) cost*
Mean (SD)	$13,462 (21,899)	$12,241 (23,165)	$50,733 (80,051)
At index
Age in years, mean (SD)	53.5 (15.0)	53.3 (13.5)	47.9 (17.5)
Gender, % female	51.4	50.6	75.0
Payer type, % commercial	96.3	97.2	87.5
Geographic region, %
Northeast	19.7	22.2	12.5
Midwest	29.0	27.8	12.5
South	41.5	40.6	75.0
West	9.8	9.4	0.0

1L = first line; 2L = second line; 3L = third line; CML = chronic myeloid leukemia; TKI = tyrosine kinase inhibitor; CCI = Charlson Comorbidity Index; SD = standard deviation.

^a‘CML severity’ was defined using the approaches and diagnosis codes as described in Wu et al.21, to measure the active CML and CML-related comorbidities/complications.

^b‘Cancer complexity’ was defined using the approaches and diagnosis codes as described in Darkow et al.22, to measure the difficulty in managing a patient’s tumor.

*Pre-index costs did not include costs incurred on the index date.

Bolded values indicate statistically significant differences between 1L and 2L failures at p < 0.05 level; 3L failures were not included in the statistical comparison due to small sample size.

Table 3. Unadjusted health care resource utilization in the 1 year post-failure..

Resource Use Measures	1L Failures (N = 518)				2L Failures (N = 180)				p value for %	p value for #
	Patients with resource use		# of times services used among patients with resource use		Patients with resource use		# of times services used among patients with resource use
	N	%	Mean	SD	N	%	Mean	SD
Outpatient prescription fills	518	100.0	37.0	34.2	180	100.0	44.2	36.4	NA	0.016
Hospitalizations	120	23.2	2.0	1.6	56	31.1	1.9	1.5	0.016	0.989
ER visits	180	34.7	1.8	1.4	66	36.7	2.0	1.5	0.643	0.181
Physician office visits	509	98.3	20.0	18.3	177	98.3	24.9	20.7	NA	0.003
Outpatient surgical center visits	307	59.3	2.2	3.7	114	63.3	3.5	8.0	0.337	0.004
Lab tests and other services	512	98.8	107.8	128.6	176	97.8	148.2	173.6	NA	0.001

ER = emergency room; lab tests and other services = use of lab, pathology, radiology, injections, and all other services; NA = not applicable; SD = standard deviation.

Bolded values indicate statistically significant differences between 1L and 2L failures at p < 0.05 level; 3L failures were not included in the statistical comparison due to small sample size.

Table 4. Adjusted health care resource utilization and costs in the 1 year post treatment failure.

Predicted mean resource use per episode	All 1L w/failure (N = 518)	All 2L w/failure (N = 180)	Exponentiated parameter estimate (i.e., relative utilization for 2L:1L) (95% CI)
# of ambulatory visits	21.5	31.1	1.45 (1.26–1.67)
% of episodes with hospitalization*	22.7	32.9	1.75 (1.16–2.64)
% of episodes with ER visit*	34.0	39.0	1.26 (0.86–1.83)
Predicted mean all-cause cost per episode, in 2012 $	All 1L w/failure (N = 518)	All 2L w/failure (N = 180)	Exponentiated parameter estimate (i.e., relative cost for 2L:1L) (95% CI)*
Total health care cost	$76,559	$106,024	1.38 (1.14–1.68)
Medical cost**	$33,445	$57,979	1.73 (1.31–2.29)
Ambulatory cost	$2842	$3938	1.39 (1.15–1.67)
Outpatient pharmacy cost	$43,108	$48,669	1.13 (0.87–1.46)

1L = first line; 2L = second line; CI = confidence interval; ambulatory visits = visits to physician office and/or outpatient surgery center; ER = emergency room.

*Because of low incidence of inpatient and ER services, presence of service use (yes/no) was modeled for hospitalizations and ER visits.

**Inpatient and ER costs were not separately adjusted due to the lack of sufficient sample size (i.e., # of episodes with the event).

Figure 3. Unadjusted mean health care costs in the 1 year post TKI treatment failure by line of therapy. 1L = first line; 2L = second line; 3L = third line; ‘Medical’ = costs for medical (nonpharmacologic) services; ‘Outpatient Pharmacy’ = costs for pharmacy claims.

Table 5. Unadjusted health care costs in the 1 year post TKI treatment failure.

Cost Category	1L Failures		2L Failures		p value	Δ (2L Failures - 1L Failures)
	(N = 518)		(N = 180)
	Mean	SD	Mean	SD
Outpatient pharmacy costs	$43,089	$35,762	$48,546	$34,763	0.076	$5457
TKI	$39,482	$35,607	$44,236	$35,547	0.123	$4754
Non-TKI pharmacy	$3607	$7946	$4311	$7851	0.305	$704
Medical service costs	$35,578	$92,751	$51,078	$118,169	0.073	$15,500
Inpatient	$18,912	$72,925	$29,446	$99,331	0.131	$10,534
ER	$509	$1259	$709	$2683	0.183	$200
Ambulatory visits	$2963	$3560	$3508	$3655	0.079	$545
Physician office visits	$2198	$2578	$2783	$2942	0.012	$585
Outpatient surgeries	$764	$1949	$725	$1483	0.804	−$39
Lab tests and other services	$13,194	$26,074	$17,415	$29,524	0.071	$4221
Total costs (pharmacy + medical services)	$78,667	$98,225	$99,624	$121,183	0.021	$20,957

1L = first line; 2L = second line; TKI = tyrosine kinase inhibitor; ER = emergency room; SD = standard deviation; ambulatory visits = visits to physician office and/or outpatient surgery center; lab tests and other service use = use of lab, pathology, radiology, injections, and all other services.

Bolded values indicate statistically significant differences between 1L and 2L failures at p < 0.05 level; 3L failures were not included in the statistical comparison due to small sample size.

Wu EQ, Johnson S, Beaulieu N, et al. Healthcare resource utilization and costs associated with non-adherence to imatinib treatment in chronic myeloid leukemia patients. Curr Med Res Opin 2010;26:61-9

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