Frequently Asked Questions
Yes. Standard dosing considers only the amount of drugadministered to the patientat set times (every 8 weeks). iDose and T3 consider both amount of drug and how long the drug stays in the patient’s body. Different patients clear (eliminate) infliximab (IFX) at significantly different rates. The differencesbetween patients is what drives iDose and T3 dose recommendations. For patients that clear IFX quickly, there is a very high probability that the treatment will fail which is reflected in the historically high treatment failure rates (20-30% failure in induction and 10-20% per year in maintenance).
No. iDose and T3are not a substitutes for clinical reasoning. They are medical decision supporttools for trained clinicians. Final drug doses and/or dosing intervals for a patient must be made only after careful consideration of the full clinical status of the patient. No medical decision should be based solely upon the results provided by these software programs.
Statistically significant and clinically meaningful*reductions in both primary non-response (treatment failure during first three doses) and secondary non-response (failure after the fourth dose) are achieved when the software aids medical decision making. In addition, insurance companies have granted prior approval of dose adjustments based on iDose documented analysis.
*Strik AS, Löwenberg M, Mould DR, Berends SE, et al. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial.Scand J Gastroenterol. 2021 Feb;56(2):145-154
No. Typically, iDose and T3 subscriptions are paid by a medical practice. The software supports complex medical decision making.Each time the software is used to “analyze” laboratory results the time spent making the decision may be reimbursed by applicable insurance. (CPT Code) Alternatively, the medical decision may be reimbursed based upon the complexity of the decision, relative to other factors. (CPT Code). Compliance with the payor’s requirements should be assured prior to submitting any claim.
iDose may be used for both IFX induction (first three doses) and maintenance (all doses after the third dose). Blood samples for IFX can be drawn at any time after the previous dose. iDose is best for early treatment because patients are changing very quickly during induction. The flexibility of iDose provides timely information that is necessary during induction.
T3 is for maintenance only (all doses after the third dose) with patients having dosing intervals ofat least four (4) weeks. Blood samples for IFX must be taken just prior to the next dose. Patients who are stable don’t require as much monitoring but 10-20% of patients still fail treatment without monitoring.
Yes: When transitioning from IFX to another therapeutic, input a very low non-zero target concentration. The resulting dosing interval is the washout period, i.e., the time from the last infusion to having little or no IFX in circulation. For most patients, the standard wash-out period is at least 8 weeks, which can result in disease progression. iDose and T3 can substantially shorten this period, allowing the patient to start a new therapy more quickly.
Yes: Both iDose and T3 are regulated by the FDA under section 520(o) of Federal Food, Drug, and Cosmetic Act, Regulation of Medical and Certain Decision Support Software.
The intended use of both iDose and T3 isincluded in their definition by the Global Medical Device Nomenclature Agency.
Pharmaceutical Management Support Software, Professional Use:
A software package intended to be used exclusively by healthcare professionals in a clinical setting to facilitate pharmaceutical management decisions (e.g. dosage) by providing suggested regimes for individual patients based on their physical and laboratory data…. It is not intended to support anesthesia administration.
(Question consistently asked by iDose and T3 users)
Many medical schools focus upon the vast majority of rapidly cleared drugs where variation in drug clearance is not a significant factor within the respective patient population. However several medical schools and health systems are beginning to recognize the importance of dose intervals which was highlighted in some of the clinical trials using iDose ((link clintrials.gov numbers)).
Most drugs have relatively short dosing intervals (hours) because they clear the body rapidly (half-lives in hours). For these drugs individual patient adjustments for interpatient variability of clearance can be addressed by altering the dose amount without consideration of the dosing interval. However, most biologic drugs have relatively slow clearance (half-lives in days) and much longer dosing intervals (e.g.,eight weeks for IFX). In order to be effective, IFX must stay at or above certain levels between doses. For patients with short half-lives, simply increasing the dose does not correct for very low drug concentration at the end of the dose interval. For these biologics,individual patient dose adjustment often requires consideration of both the dose amount and the dosing interval.
The number of half-lives varies from patient to patient. Generally, the span of 4 to 5 half-lives is sufficient to clear most drugs. However, IFX clearance is more complex than most drugs. IFX actually has two half-lives, one is fast and the other is slower. The “effective” half-life is a weighted average of the two half-lives. Doubling the IFX dose amount provides less than one additional effective half-life of coverage. The real-world range of effective half-lives for patients treated with IFX is from 1.8 in patients with acute severe disease to 15.5 days in patients who are stable with good quality remission. For some of these patients increasing the dose amount is insufficient to maintain therapeutic coverage within the eight week dosing interval and consideration of modifying the interval is important to getting a good clinical outcome.
These tools inform the decision making process, allowing health care providers to consider both drug amount and dosing interval for individual patients without having to manually calculate the individual patient’s effective half-life.
Both applications help the physician analyze the data, and output a variety of dosing regimens (i.e., different combinations of dose amount and interval) that will achieve the physician-selected trough concentration. The results from iDose and T3 can be easily documented for medical reimbursement.
Yes: Effective half-life valuesused to inform the approved IFX label, range from 7.7 to 9.5 days (IFX package insert). Recall that the drug is cleared in 4-5 half-lives and even with a half-life of 9.5 days, the drug will be gone before the label 8 week dose interval. In clinical trials of iDose, approximately 90% of patients were dosed using off-label dosing. Patients treated using iDose had higher remission rate, less anti-drug antibodies and stayed on IFX longer than historical data using the labeled dose.
Real-world data used to qualifythe iDose and T3 algorithmscontaineffective half-life values ranging from 1.8 to 15.5 days.
No: Trough concentrations (a.k.a. minimum therapeutic concentrations, desired target concentrations, desired levels) are determined by the physician. Target concentration values are input only.
For iDose: A IFX concentration is a preferred input. iDose inputs include a variety of other IFX clearance covariates such as patient weight and albumin. Inputs default to nominal values for missing data. iDose performance is enhanced when individual patient concentration data are provided. However, in the treatment of acute severe ulcerative colitis patients, after entry of all available data, iDose has been used successfully prior to the first IFX dose to determine effective treatment plans.
For T3: An IFX concentration is a necessary T3 input. T3 inputs include only one other IFX covariate: weight. Missing data do not default to nominal values.
Both iDose and T3 will be rolling out adalimumab shortly, and have other commonly used biologics in the pipeline including vedolizumab. Stay tuned!
