Application of a validated algorithm to estimate the effectiveness and cost of biologics for rheumatoid arthritis in the US pharmacy benefit manager context

Figures & data

Table 1 Components of the effectiveness algorithm, assessed between the index date and the outcome visit date approximately 1 year later

Criterionb	Description and implementation
High adherence to index drug (required)	For etanercept, adalimumab, and oral medications, must be ≥80% adherent to therapy, calculated as a medication possession ratio^Citation19 For infliximab, must have received at least the number of infusions expected between the index and outcome visit dates to conform to a schedule of 0, 2, 6, and 14 weeks, and every 8 weeks thereafter For abatacept, must have received the number of infusions expected between the index and outcome visit dates to conform to a schedule of once-monthly dosing; missing one infusion is permissible For rituximab, criterion is not applicable
Biologic switch or add (prohibited)	Between the index and outcome visit dates, patient cannot initiate therapy with a new biologic agent
Addition of a new nonbiologic DMARD (prohibited)	Between the index and outcome visit dates, patient cannot initiate therapy with a new nonbiologic DMARD (methotrexate, sulfasalazine, leflunomide, or hydroxychloroquine) that they were not already taking during the 6 months prior to the index date
Increase in biologic dose or frequency (prohibited)	For etanercept and adalimumab, dose escalation of etanercept to 50 mg twice weekly or adalimumab 40 mg once weekly is prohibited For infliximab, difference between ending and starting dose, with each dose rounded up to the nearest 100 mg, cannot be ≥100 mg. The number of infusions must be within 120% of the number expected, assuming a 0-, 2-, or 6-week load and an 8-week infusion schedule For abatacept, difference between ending and starting dose cannot be ≥100 mg For rituximab, criterion is not applicable
More than one glucocorticoid joint injection (prohibited)	Cannot receive glucocorticoid injectionsc on more than one unique calendar day between the index date +90 days and the outcome visit date, inclusive
Increase in dose of oral glucocorticoid (prohibited)	For patients who received no prescriptions for oral glucocorticoids during the 6 months prior to the index date, cannot have received more than 30 days of oral glucocorticoids between the index date +90 days and the outcome visit date, inclusive For patients who received prescriptions for oral glucocorticoids in the 6 months prior to the index date, the cumulative glucocorticoid dose in the 6 months prior to the outcome visit date must be similar (ie, within 120%) to the cumulative dose in the 6 months prior to the index visit date

Notes: Reproduced from Curtis JR, Baddley JW, Yang S, et al. Derivation and preliminary validation of an administrative claims-based algorithm for the effectiveness of medications for rheumatoid arthritis. Arthritis Res Ther. 2011;13:R155 (BioMed Central);¹⁴

b all criteria must be satisfied to have met the effectiveness algorithm;

c glucocorticoid injection Current Procedural Terminology codes: 20600, 20605, 20610.

Abbreviation: DMARD, disease-modifying antirheumatic drug.

Table 2 Population attrition by application of inclusion and exclusion criteria

Reason for exclusion	Patients excluded		Patients remaining
	n	%	n	%
Patients with at least one RA diagnosis since January 1, 2007			97,816
No RA-related biologic claim throughout study period	86,123	88.05	11,693	11.95
Age <18 or >63 years on index	2,418	20.68	9,275	79.32
Continuously enrolled <180 days pre-index	6,189	66.73	3,086	33.27
Continuously enrolled <365 days post-index	1,245	40.34	1,841	59.66
No diagnosis of RA pre-index	451	24.50	1,390	75.50
Two or more RA biologics on the index date	0	0.00	1,390	100.00
RA-related biologic exposure pre-index	0	0.00	1,390	100.00
Index claim for RA-related biologics before US FDA approval	0	0.00	1,390	100.00
Had diagnosis for another disease indicationa pre-index	154	11.08	1,236	88.92
Had index biologic with sample size <100b	146	11.81	1,090	88.19

Notes:

a Non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, ulcerative colitis, Crohn’s disease, ankylosing spondylitis;

b anakinra, n=2; certolizumab, n=17; golimumab, n=33; rituximab, n=78; tocilizumab, n=16.

Abbreviations: RA, rheumatoid arthritis; US FDA, United States Food and Drug Administration.

Table 3 Baseline characteristics

	All (n=1,090)	SC (n=785)	IV (n=305)	ETN (n=440)	ADA (n=345)	IFX (n=201)	ABA (n=104)
Agea,b	49.66±9.44	49.25±9.43	50.72±9.4	48.99±9.82	49.58±8.9	49.77±9.52	52.57±8.93
Age categoryb
18–34	8.26	8.79	6.89	10.45	6.67	7.46	5.77
35–44	17.8	18.73	15.41	18.64	18.84	17.41	11.54
45–54	38.53	39.11	37.05	37.95	40.58	40.3	30.77
55–63	35.41	33.38	40.66	32.95	33.91	34.83	51.92
Female	77.52	76.43	80.33	77.73	74.78	78.61	83.65
Male	22.48	23.57	19.67	22.27	25.22	21.39	16.35
Regiona–c
Northeast	28.17	26.24	33.11	23.64	29.57	33.33	32.69
South	20.46	21.78	17.05	20.45	23.48	15.42	20.19
Midwest	34.86	36.56	30.49	37.73	35.07	34.33	23.08
West	14.4	13.12	17.7	15.91	9.57	14.93	23.08
Other	2.11	2.29	1.64	2.27	2.32	1.99	0.96
Charlson Comorbidity Index	0.8±1.2	0.8±1.2	0.9±1.3	0.8±1.2	0.8±1.2	0.9±1.3	1.1±1.3

Notes: Values are presented as percent of patients except for age, which is the mean ± standard deviation years, and Charlson Comorbidity Index, which is the mean ± standard deviation units;

a P<0.05 SC versus IV;

b P<0.05 ETN versus ABA;

c P<0.05 ETN versus ADA.

Abbreviations: ABA, abatacept; ADA, adalimumab; ETN, etanercept; IFX, infliximab; IV, intravenous; SC, subcutaneous.

Table 4 DMARD use during the pre-index period (180 days)

	All (n=1,090)	SC (n=785)	IV (n=305)	P-value IV versus SC	ETN (n=440)	ADA (n=345)	P-value ETN versus ADA	IFX (n=201)	P-value ETN versus IFX	ABA (n=104)	P-value ETN versus ABA
Any DMARD	72.29	81.91	47.54	<0.001	80.68	83.48	0.31	52.24	<0.001	38.46	<0.001
Methotrexate	58.26	66.62	36.72	<0.001	65.45	68.12	0.43	44.28	<0.001	66.62	<0.001
Hydroxychloroquine	25.96	30.57	14.1	<0.001	33.18	27.25	0.07	14.43	<0.001	30.57	<0.001
Leflunomide	10.83	12.61	6.23	0.002	10.91	14.78	0.10	4.98	0.02	12.61	0.50
Sulfasalazine	10.00	11.34	6.56	0.02	11.82	10.72	0.63	6.97	0.06	11.34	0.07

Note: Values are presented as percent of patients or P-value.

Abbreviations: ABA, abatacept; ADA, adalimumab; DMARD, disease-modifying antirheumatic drug; ETN, etanercept; IFX, infliximab; IV, intravenous; SC, subcutaneous.

Figure 1 Effectiveness according to the algorithm in percentage of patients.

Abbreviation: IV, intravenous.

Table 5 Effectiveness according to the validated algorithm

	All (n=1,090)	SC (n=785)	IV (n=305)	P-value IV versus SC	ETN (n=440)	ADA (n=345)	P-value ETN versus ADA	IFX (n=201)	P-value ETN versus IFX	ABA (n=104)	P-value ETN versus ABA
Effectiveness, % patients	32.2	35.9	22.6	<0.001	36.4	35.4	0.77	21.9	<0.001	24.0	0.02
Reasons for deeming therapy not effective, % patients
Low adherence	51.4	50.2	54.4	0.21	50.5	49.9	0.87	49.8	0.87	63.5	0.02
Increased biologic dose	10.1	3.2	27.9	<0.001	0.5	6.7	<0.001	38.8	<0.001	6.7	<0.001
Biologic switch	18.4	18.7	17.7	0.70	19.1	18.3	0.77	18.9	0.96	15.4	0.38
New DMARD	15.4	16.4	12.8	0.13	15.2	18.0	0.30	12.4	0.35	13.5	0.65
Increase in glucocorticoid dose	11.7	12.1	10.5	0.46	13.0	11.0	0.41	10.0	0.28	11.5	0.70
Multiple joint injections	7.8	6.2	11.8	0.002	6.4	6.1	0.87	9.5	0.16	16.4	<0.001

Note: Values are presented as percent of patients or P-value.

Abbreviations: ABA, abatacept; ADA, adalimumab; DMARD, disease-modifying antirheumatic drug; ETN, etanercept; IFX, infliximab; IV, intravenous; SC, subcutaneous.

Figure 2 Cost per effectively treated patient according to the algorithm in US dollars for all patients, by method of administration and by biologic.

Abbreviation: IV, intravenous.

Figure 3 Cost per effectively treated patient according to the algorithm as a percentage in relation to ETN by biologic.

Abbreviation: ETN, etanercept.

SikkaRXiaFAubertREEstimating medication persistency using administrative claims dataAm J Manag Care200511744945716044982

 PubMed Web of Science ®Google Scholar

CurtisJRBaddleyJWYangSDerivation and preliminary validation of an administrative claims-based algorithm for the effectiveness of medications for rheumatoid arthritisArthritis Res Ther2011135R15521933396

 PubMed Web of Science ®Google Scholar