Pharmacokinetic modeling systems for improved therapeutic dosing

A method for treating an immune-mediated inflammatory disease in a subject, the method comprising:

• (a) analyzing one or more biological samples obtained from a subject receiving a biologic drug for treatment of an immune-mediated inflammatory disease, wherein the analyzing comprises:
• (i) obtaining or having obtained the one or more biological samples from the subject prior to a third dose of the biologic drug in an induction phase of the treatment;
• and
• (ii) quantifying or having quantified analytes in the biological sample, wherein the analytes comprise:
• (1) a level of the biologic drug, (2) a level of autoantibodies against the biologic drug, and (3) a level of albumin, wherein the subject has received the treatment for the immune-mediated inflammatory disease that comprises a current dose of the biologic drug administered to or by the subject at a current inter-dose interval;
• (b) determining an estimated dose and an estimated inter-dose interval of the biologic drug for the subject based, at least in part on, (1) the level of the biologic drug, the level of the autoantibodies, and the level of albumin quantified in (a)(ii), and (2) the current dose of the biologic drug and the current inter-dose interval, wherein the estimated dose at the estimated inter-dose interval is predicted to result in a pre-specified threshold concentration of the biologic drug in the subject at one or more comparing time points;
• and
• (c) administering the biologic drug to the subject at the estimated dose and estimated inter-dose interval.

A method for identifying an optimal dose and inter-dose interval for treating an immune mediated inflammatory disease in a subject, the method comprising:

• (a) analyzing one or more biological samples obtained from a subject receiving a biologic drug for treatment of an immune-mediated inflammatory disease, wherein the analyzing comprises:
• (i) obtaining or having obtained the one or more biological samples from the subject prior to a third dose of the biologic drug in an induction phase of the treatment;
• and
• (ii) quantifying or having quantified analytes in the biological sample, wherein the analytes comprise:
• (1) a level of the biologic drug, (2) a level of autoantibodies against the biologic drug, and (3) a level of albumin, wherein the subject has received the treatment for the immune-mediated inflammatory disease that comprises a current dose of the biologic drug administered to or by the subject at a current inter-dose interval;
• (b) determining an estimated concentration time course curve of the biologic drug in the subject based, at least in part on, (1) the level of the biologic drug, the level of the autoantibodies, and the level of albumin quantified in (a)(ii), and (2) the current weight-based dose of the biologic drug and the current inter-dose interval,
• wherein the optimal dose and inter-dose interval is identified such that the estimated concentration of the biologic drug on the time course curve at one or more comparing time points is above a pre-specified threshold concentration.

A method for identifying an optimal dose and inter-dose interval for treating an immune mediated inflammatory disease in a subject, the method comprising:

• (a) analyzing one or more biological samples obtained from a subject receiving a biologic drug for treatment of an immune-mediated inflammatory disease, wherein the analyzing comprises:
• (i) obtaining or having obtained the one or more biological samples from the subject prior to a third dose of the biologic drug in an induction phase of the treatment;
• and
• (ii) quantifying or having quantified analytes in the biological sample, wherein the analytes comprise:
• (1) a level of a biologic drug, (2) a level of autoantibodies against the biologic drug, and (3) a level of albumin, wherein the subject has received a treatment for the immune-mediated inflammatory disease that comprises a current dose of the biologic drug administered to or by the subject at a current inter-dose interval;
• (b) determining an estimated dose and an estimated inter-dose interval of the biologic drug for the subject based, at least in part on, (1) the level of the biologic drug, the level of the autoantibodies, and the level of albumin quantified in (a)(ii), and (2) the current dose of the biologic drug and the current inter-dose interval, wherein the estimated dose at the estimated inter-dose interval is predicted to result in a pre-specified threshold concentration of the biologic drug in the subject at one or more comparing time points.

A method for identifying a dose and an inter-dose interval for achieving a threshold biologic drug concentration value in a subject, the method comprising:

• (a) initializing a model of a biologic drug concentration profile for a biologic drug, wherein the model comprises data received from a reference population that were or currently are being treated with the biologic drug for treatment of an immune-mediated inflammatory disease;
• (b) generating subject specific parameters relating to pharmacokinetic performance of the biologic drug in the subject, wherein generating the subject specific parameters is performed using one or more biological samples obtained from the subject prior to a third dose of the biologic drug in an induction phase of the treatment of the immune-mediated inflammatory disease;
• (c) simulating the biologic drug concentration profile for the subject based on the subject specific parameters and the data from the reference population;
• and
• (d) estimating a dose of the biologic drug at an inter-dose interval to achieve the threshold biologic drug concentration value in the subject at one or more comparing time points with the model, wherein the threshold biologic drug concentration is sufficient to treat the immune-mediated inflammatory disease in the subject.

A computer-implemented method of training an algorithm that determines a biologic drug profile of a biologic drug for a subject having an immune-mediated inflammatory disease, the method comprising:

• (a) receiving data from a database, wherein the data is related to a pharmacokinetic performance of the biologic drug in individuals from a reference population having the immune-mediated inflammatory disease that have been treated with the biologic drug;
• (b) establishing a first set of parameter estimates from the data;
• (c) deriving a second set of parameter estimates for a model based at least in part on the first set of parameter estimates;
• (d) receiving subject specific data related to the pharmacokinetic performance of the biologic drug in the subject, wherein the subject specific data is received by obtaining one or more biological samples from the subject prior to a third dose of the biologic drug in an induction phase of a treatment for the immune-mediated inflammatory bowel disease;
• (e) updating the model based at least in part on the subject specific data received in (d);
• and
• (f) determining a biologic drug profile for the subject with the model, wherein the biologic drug profile comprises a dose of the biologic drug at an inter-dose interval estimated to achieve a threshold biologic drug concentration value in the subject at one or more comparing time points that is sufficient to treat the immune-mediated inflammatory disease in the subject.

A computer-implemented system for determining a biologic drug profile of a biologic drug for a subject having an immune-mediated inflammatory disease, the computer-implemented system comprising:

• a computing device comprising at least one processor;
• an operating system configured to perform executable instructions;
• a memory;
• and
• a computer program including instructions executable by the computing device to create an application comprising:
• a software module configured to initialize a model of a biologic drug concentration profile for a biologic drug, wherein the model comprises data related to a pharmacokinetic performance of the biologic drug in individuals from a reference population having the immune-mediated inflammatory disease that have been treated with the biologic drug;
• a software module configured to establish a first set of parameter estimates from the data;
• a software module configured to derive a second set of parameter estimates for a model based at least in part on the first set of parameter estimates;
• a software module configured to receive subject specific data related to the pharmacokinetic performance of the biologic drug in the subject, wherein the subject specific data is received by obtaining one or more biological samples from the subject prior to a third dose of the biologic drug in an induction phase of a treatment of the immune-mediated inflammatory bowel disease;
• and
• a software module configured to update the model based at least in part on the subject specific data;
• and
• a software module configured to determine a biologic drug profile for the subject, wherein the biologic drug profile comprises a dose of the biologic drug at an inter-dose interval estimated to achieve a threshold biologic drug concentration value in the subject at one or more comparing time points that is sufficient to treat the immune-mediated inflammatory disease in the subject.

Non-transitory computer-readable storage media encoded with a computer program including instructions executable by one or more processors for identifying a dose and an inter-dose interval for achieving a threshold biologic drug concentration value in a subject, wherein the instructions comprise:

• (a) initializing a model of a biologic drug concentration profile for a biologic drug, wherein the model comprises data received from a reference population that were or currently are being treated with the biologic drug for treatment of an immune-mediated inflammatory disease;
• (b) generating subject specific parameters relating to pharmacokinetic performance of the biologic drug in the subject wherein generating the subject specific parameters is performed using one or more biological samples obtained from the subject prior to a third dose of the biologic drug in an induction phase of the treatment of the immune-mediated inflammatory disease;
• (c) simulating the biologic drug concentration profile for the subject based on the subject specific parameters and the data from the reference population;
• and
• (d) estimating a dose of the biologic drug at an inter-dose interval to achieve the threshold biologic drug concentration value in the subject at one or more comparing time points with the model, wherein the threshold biologic drug concentration is sufficient to treat the immune-mediated inflammatory disease in the subject.

A method of treating an immune-mediated inflammatory disease of a subject, the method comprising:

• (a) performing or having performed an immunoassay on one or more biological samples obtained from the subject to determine a level of albumin and a level of a biologic drug that are predictive of clinical remission of the immune-mediated inflammatory disease of the subject, wherein the one or more biological samples is obtained from the subject prior to a third dose of the biologic drug in an induction phase of a treatment for the immune-mediated inflammatory disease, and wherein the subject is currently receiving the biologic drug for the treatment of the immune-mediated inflammatory disease;
• (b) estimating a clearance rate at one or more comparing time points of the biologic drug for the subject based, at least in part, on the level of albumin determined in (a) and a weight of the subject;
• and
• (c) if the level of the biologic drug is above a cutoff level in milligrams/L (mg/L) and the clearance rate at the one or more comparing time points is estimated to be below a threshold level of liters (L)/day, then administering a lower dose of the biologic drug to the subject or discontinuing the treatment of the immune-mediated inflammatory disease with the biologic drug;
• or
• (d) if the level of the biologic drug is below the cutoff level and the clearance rate at the one or more comparing time points is estimated to be above the threshold level, then administering the biologic drug to the subject in the same or higher dose than a dose of the biologic drug the subject is currently receiving, or administering a different drug to the subject, wherein the threshold level and the cutoff level are derived from an optical Youden index.