Table 1.

Indicators of suboptimal biological or conventional treatment among patients with CD during the landmark year (12 months following initiation of index agent).

Biologic and conventional cohorts
Nonadherence	Among patients with at least 2 claims for the index agent, medication possession ratio (MPR) <80% (MPR: sum of index agent days of supply divided by the number of days between the first and last day of supply of the index agent within the landmark period)
Dose escalationa	Biologic: A reference daily exposure,b,c to the index agent was calculated during the 90 days after the index date. Dose escalation occurred when the daily exposure after the 90-day period was 50% above the reference daily exposure for a fill date
	Conventional: A reference daily exposureb to the index agent was calculated during the 90 days (immunomodulators) or 45 days (5-ASA) after the index date. Dose escalation occurred when the daily exposure was 10% (immunomodulators) or 50% (5-ASA) above the reference daily exposure for a fill date; for mesalamine dose escalation also occurred with combination therapy oral + rectal independently from the dose
Restart	Among patients with discontinuation of the index agent (ie, 90 days gap in the day of supply), ≥1 fill for the index medication between the discontinuation date and the end of the landmark year
Chronic corticosteroid use	≥90 days of nonoverlapping days of supply of corticosteroids cumulated over the landmark year
Augmentationa	Biologic: To exclude combination therapies, in the 30 days following the index date (buffer period), immunomodulators use was recorded and these agents could not be candidate for augmentation. Following the buffer period, augmentation was defined as ≥60 days concomitant use of an immunomodulator candidate for augmentation
	Conventional: ≥60 days of concomitant use of a biologic candidate for augmentation following a buffer period of 30 days after the index date
≥1 surgery for CD, ≥2 ED visits for CD, ≥1 IP for CD	Defined based on medical claims with an ICD-9 diagnosis of 555.x or an ICD-10 diagnosis of K50.x during the landmark year
Biologic cohort
Switch to conventional	Among patients with discontinuation of the index biologic (ie, 90 days gap in the day of supply), ≥1 fill for a conventional agent (ie, 5-ASA or immunomodulator) between the discontinuation date and the end of the landmark year
Switch to a different biologic	Among patients with discontinuation of the index biologic (ie, 90 days gap in the day of supply), ≥1 fill for a biologic agent other than the index biologic between the discontinuation date and the end of the landmark year
Inadequate induction	Depending on the index agent, either the number of fills (infliximab, vedolizumab) or the total dose (adalimumab, certolizumab) in the induction period per label with 25% grace period (eg, 6 weeks + 1.5 week buffer for infliximab) was counted. Inadequate induction dose occurred when the number of fills was fewer than expected per label (eg, <3 fills for infliximab or <240 mg for adalimumab) during that period. For ustekinumab, inadequate induction occurred if the record of use on the index date was not for an intravenous administration. For natalizumab, the indicator could not be estimated as induction is not indicated
Conventional cohort
Switch from index treatment	Among patients with discontinuation of the index conventional (ie, 90 days gap in the day of supply), ≥1 fill for an agent different than the index agent mechanism of action (including both conventional and biologic agents) between the discontinuation date and the end of the landmark year
Cycling on index treatment mechanism of action	Among patients with discontinuation of the index conventional (ie, 90 days gap in the day of supply), ≥1 fill for an agent in the index treatment mechanism of action (ie, 5-ASA or immunomodulators, excluding the index agent) between the discontinuation date and the end of the landmark year

Abbreviations: 5-ASA, 5-aminosalicylic acid; CD, Crohn’s disease; ED, emergency department; ICD-9, International Classification of Diseases, version 9; ICD-10, International Classification of Diseases, version 10; IP, inpatient.

Evaluated during the first continuous episode of use of the index therapy (ie, without a gap of ≥90 consecutive days between days of index treatment supply or between the last day of supply and the end of the landmark period). If there was no discontinuation, the first continuous episode of use of the index therapy was censored at the end of the landmark year.

In the pharmacy claims, the ratio of the total dose and days of supply at a claim was used to estimate the daily exposure, and in the medical claims the ratio of the number of units and time interval between claims was used to estimate the daily exposure. The weight of the patient was assumed to be constant.

For natalizumab, there was no reference daily exposure as induction is not indicated for this drug (ie, the reference daily dose was calculated based on the index date).