Method and system for use in treating a patient with immunosuppresants using whole blood level criteria to prevent an adverse immune response

• US 5,694,950 A
• Filed: 08/16/1994
• Issued: 12/09/1997
• Est. Priority Date: 08/21/1992
• Status: Expired due to Fees

• Current Assignee: J & W Mcmichael Software Incorporated
• Original Assignee: J & W Mcmichael Software Incorporated
• Inventors: McMichael, John Patrick
• Primary Examiner(s): Lacyk, John P.
• Application Number:
  US08/291,223
• Time in Patent Office: 1,211 Days
• Field of Search: 128/897-8, 364/413.01-413.02, 540/455
• US Class Current: 128/898
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions

Abstract

A method and system for use in treating a patient with an immunosuppressant to prevent an adverse immune response, either a rejection of a transplanted organ or an attack on the patient'"'"'s body by its own immune system caused by an autoimmune disease, without unduly suppressing the ability of the patient'"'"'s immune system to combat infection. The method employs an expert system to provide non-numerical information concerning the course of action to be taken with respect to a patient'"'"'s immunosuppressant treatment, at a given time, including, in particular, an instruction on whether the immunosuppressant dosage being administered to the patient should be changed, and if so how. That instruction is determined by the expert system through analysis of standardized characterizations assigned to standardized patient examination criteria including levels of the immunosuppressant in blood plasma and whole blood. The method also employs a means for determining the actual numerical immunosuppressant dosage the patient should receive at a given time.

Claims

1. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the immune system to combat infection, comprising the step of:

(a) administering an initial dose of an immunosuppressant to the patient;

(b) examining the patient to determine information concerning patient examination criteria, wherein the patient examination criteria comprises toxicity and a blood level of the immunosuppressant;

(c) assigning a characterization to each of the patient examination criteria, each such characterization being selected from a predetermined standardized range of characterizations applicable to each patient examination criterion;

(d) providing the assigned characterizations to a computing device comprising;

a knowledge base comprising rules which include one of a plurality of treatment instructions in response to at least one of various combinations of the characterizations which can be assigned to the patient examination criteria, and

an expert computer program including a first routine for prompting, through an output means, a user to enter, through an input means, the assigned characterizations;

a second routine for selecting a treatment instruction by locating a rule which covers the assigned characterizations, and thereby determines the treatment instruction; and

a third routine for communicating the treatment instruction to the output means;

(e) receiving from the computing device the treatment instruction; and

(f) administering a next dose of the immunosuppressant to the patient in accordance with the treatment instruction.

2. A method according to claim 1, which comprises the method comprising the additional steps, after step (e) and before step (f), of:

(g) providing to the computing device data relating to a next immunosuppressant dosage determination, when the treatment instruction requires that the dosage be changed; and

(h) receiving from the computing device the next immunosuppressant dosage, if one is determined;

wherein the expert computer program comprises a fourth routine for determining a next immunosuppressant dosage to be administered to the patient;

wherein the expert computer program contains at least one additional routine for receiving the data through the input means and communicating the next immunosuppressant dosage to the output means; and

wherein the next immunosuppressant dose administered to the patient is determined in accordance with the treatment instruction, and the next immunosuppressant dosage, if one is determined.

3. A method according to claim 2, wherein the patient is selected from the group consisting of heart and kidney transplant patients and the patient examination criteria further comprises a rejection criterion.

4. A method according to claim 2, wherein the patient is a liver transplant patient and the patient examination criteria further comprise a rejection criterion, a creatinine level criterion, a bilirubin level criterion, and a SGOT and SGPT levels criterion.

5. A method according to claim 2, wherein the patient is afflicted with an autoimmune disease and the patient examination criteria further comprises a desired effect criterion.

6. A method according to claim 2, wherein the blood level is the blood plasma level of the immunosuppressant in the blood of the patient.

7. A method according to claim 2, wherein the blood level is the whole blood level of the immunosuppressant in the blood of the patient.

8. A method according to claim 2, wherein steps (b) through (h) are systematically repeated throughout the remainder of the patient'"'"'s life.

9. A method according to claim 1, wherein the patient is an organ transplant recipient and steps (b) through (f) are repeated every day for the first two weeks after the patient has been administered the initial dose of the immunosuppressant, then twice a week for the next two weeks, then weekly for the next two months, and then monthly for the rest of the patient'"'"'s life.

10. A method according to claim 2, wherein the patient is an organ transplant recipient and steps (b) through (h) are repeated every day for the first two weeks after the patient has been administered the initial dose of the immunosuppressant, then twice a week for the next two weeks, then weekly for the next two months, and then monthly for the rest of the patient'"'"'s life.

11. A method according to claim 1, wherein the patient is afflicted with an autoimmune disease and steps (b) through (f) are repeated twice a week for the first two weeks after the patient has been administered the initial dose of the immunosuppressant, then weekly for the next month, and then monthly for the rest of the patient'"'"'s life.

12. A method according to claim 2, wherein the patient is afflicted with an autoimmune disease and steps (b) through (h) are repeated twice a week for the first two weeks after the patient has been administered the initial dose of the immunosuppressant, then weekly for the next month, and then monthly for the rest of the patient'"'"'s life.

13. A method according to claim 7, wherein the immunosuppressant is Cyclosporin and wherein the data comprises a current Cyclosporin dosage for the patient, a current Cyclosporin whole blood level for the patient and a desired Cyclosporin level for the patient;

and

wherein the fourth routine of the expert computer program determines the next Cyclosporin dosage by employing the following relationship;

space="preserve" listing-type="equation">ND=CD-((((CL-DL)/CL)/(2.5+(CD/1500)×

2.5))CD)+((0.2×

CD)×

(((1+d)-(1+e))/abs((1+d))))

wherein,

ND=the patient'"'"'s next Cyclosporin dosage,

CD=the patient'"'"'s current Cyclosporin dosage,

CL=the patient'"'"'s current Cyclosporin whole blood level, and

DL=the desired Cyclosporin level for the patient,

RD=the patient'"'"'s previous Cyclosporin whole blood level

e=CL-RD

d=DL-RD.

14. A method according to claim 7 wherein the immunosuppressant is FK 506 and wherein the data comprise, the current FK 506 dosage for the patient, current FK 506 whole blood level for the patient and a desired FK 506 level for the patient;

and

wherein the fourth routine of the expert computer program determines the next FK 506 dosage by employing the following relationship;

space="preserve" listing-type="equation">ND=CD-((((CL-DL)/CL)/(1+(CD/40)))/CD)+((0.2×

CD)×

(((1+d)-(1+e))/abs((1+d))))

wherein,

ND=the next FK 506 dosage

CD=the patient'"'"'s current FK 506 dosage,

CL=the patient'"'"'s current FK 506 whole blood level,

DL=the desired FK 506 level for the patient,

RD=the patient'"'"'s previous FK 506 whole blood level,

e=CL-RD, and

d=DL-RD.

15. A method according to claim 7 wherein the immunosuppressant is Rapamycin and wherein the data comprise, the current Rapamycin dosage for the patient, current Rapamycin whole blood level for the patient and a desired Rapamycin level for the patient;

and

wherein the fourth routine of the expert computer program determines the next Rapamycin dosage by employing the following relationship;

For RPM;

space="preserve" listing-type="equation">ND=CD-((((CL-DL)/CL)/(1+(CD/30)))/CD)+((0.2×

CD)×

(((1+d)-(1+e))/abs((1+d))))

wherein

ND=the next RPM dosage,

CD=the patient'"'"'s current RPM dosage,

CL=the patient'"'"'s current RPM whole blood level,

DL=the desired RPM whole blood level for the patient,

RD=the patient'"'"'s previous RPM whole blood level,

e=CL-RD, and

d=DL-RD.

16. A method according to claims 1, wherein the patient is also treated with a dosage of at least one additional immunosuppressant.

17. A method according to claim 16, wherein the additional immunosuppressant is prednisone.

18. A method according to claim 17, wherein the computing device provides a prednisone treatment instruction after (i) the patient has received an initial dose of prednisone, (ii) a prednisone dosage criterion is assigned a characterization from a predetermined range of standardized prednisone characterizations, and (iii) the characterization assigned to the prednisone dosage criterion is provided to the computing device in the first routine;

the prednisone treatment instruction being provided through means of a first prednisone treatment instruction routine which searches through a prednisone treatment knowledge base containing prednisone treatment rules until a prednisone treatment rule is found which covers the characterizations assigned to an efficacy criterion and the prednisone dosage criterion, and thereby determines the prednisone treatment instruction; and

a second prednisone treatment routine for communicating the prednisone treatment instruction to the output means;

wherein the prednisone treatment instruction rules include one of a plurality of prednisone treatment instructions in response to at least one of various combinations of characterizations which can be assigned to the efficacy criterion and the prednisone dosage criterion.

19. A method according to claim 18, wherein the patient is the recipient of a transplanted organ and the efficacy criterion is a rejection criterion.

20. A method according to claim 18, wherein the patient is afflicted with an autoimmune disease and the efficacy criterion is a desired effect criterion.

21. A method according to claim 18, wherein the computing device provides a next prednisone dosage, if a decrease in the prednisone dosage is required by the prednisone treatment instruction.

22. A method according to claim 1, wherein the computing device determines at least one characterization to be assigned to a toxicity criterion through means of additional expert computer program routines comprising:

a first routine for receiving characterizations assigned to toxicity determination criteria;

a second routine which searches through a toxicity determination knowledge base containing toxicity determination rules until a toxicity determination rule is found which covers the toxicity determination characterizations assigned to the toxicity determination criteria, and thereby determines at least one characterization to be assigned to the toxicity criterion; and

a third routine for communicating to the output means the characterization to be assigned to the toxicity criterion;

wherein the toxicity determination rules include at least one of the characterizations which can be assigned to the toxicity criterion in response to at least one of various combinations of the characterizations which can be assigned to the toxicity determination criteria.

23. A method according to claim 22, wherein the toxicity determination criteria comprise a tingling/loss of sensation toxicity determination criterion, a tremor toxicity determination criterion, a trouble sleeping toxicity determination criterion, a diabetogenicity toxicity determination criterion, and a change in creatinine level toxicity determination criterion.

24. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the immune system to combat infection, comprising the steps of:

(a) administering an initial dose of an immunosuppressant to the patient;

(b) examining the patient to determine a current immunosuppressant whole blood level for the patient;

(c) assigning a characterization to the patient'"'"'s current immunosuppressant whole blood level from a predetermined standardized range of characterizations;

(d) providing the patient'"'"'s current immunosuppressant dosage and the characterization assigned to the patient'"'"'s current immunosuppressant whole blood level to a computing device comprising;

a knowledge base comprising rules which include one of a finite number of values for a decreased next immunosuppressant dosage in response to at least one of various combinations of characterizations which can be assigned to the patient'"'"'s current immunosuppressant whole blood level and values for the patient'"'"'s current immunosuppressant dosage; and

an expert computer program including a first routine for prompting, through an output means, a user to enter, through an input means, the patient'"'"'s current dosage and the characterization assigned to the patient'"'"'s current immunosuppressant whole blood level;

a second routine for selecting the next immunosuppressant dosage by locating the rule which covers the patient'"'"'s current immunosuppressant dosage and the characterization assigned to the patient'"'"'s current immunosuppressant whole blood level, and thereby determines the decreased next immunosuppressant dosage; and

a third routine for communicating the decreased next immunosuppressant dosage to the output means;

(e) receiving from the computing device the decreased next immunosuppressant dosage; and

(f) administering a next immunosuppressant dose in accordance with the decreased next immunosuppressant dosage determined by the computing device.

25. A method according to claim 24, wherein the immunosuppressant is FK 506.

26. A method according to claim 24, wherein the immunosuppressant is Rapamycin.

27. A method according to claim 24, wherein the immunosuppressant is Cyclosporin.

28. A method according to claim 24, wherein the patient is also treated with a dosage of at least one additional immunosuppressant agent.

29. A method according to claim 28, wherein the immunosuppressant agent is prednisone.

30. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the immune system to combat infection, comprising the steps of:

(a) administering an initial dose of FK 506 to the patient;

(b) examining the patient to determine a current FK 506 whole blood level for the patient;

(c) determining a desired FK 506 level for the patient;

(d) employing the following relationship along with the patient'"'"'s current FK 506 dosage, the patient'"'"'s current FK 506 whole blood level, and the desired FK 506 level for the patient to determine a next FK 506 dosage;

space="preserve" listing-type="equation">ND=CD-((((CL-DL)/CL)/(1+(CD/40)))/CD)+((0.2×

CD)×

(((1+d)-(1+e))/abs((1+d))))

wherein

ND=the next FK 506 dosage

CD=the patient'"'"'s current FK 506 dosage,

CL=the patient'"'"'s current FK 506 whole blood level,

DL=the desired FK 506 level for the patient,

RD=the patient'"'"'s previous FK 506 whole blood level

e=CL-RD

d=DL-RD

(e) administering a next dose of FK 506 to the patient in accordance with the next FK 506 dosage determined from the relationship.

31. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the immune system to combat infection, comprising the steps of:

(a) administering an initial dose of Rapamycin to the patient;

(b) examining the patient to determine a current Rapamycin whole blood level for the patient;

(c) determining a desired Rapamycin level for the patient;

(d) employing the following relationship along with the patient'"'"'s current Rapamycin dosage, the patient'"'"'s current Rapamycin whole blood level, and the desired Rapamycin level for the patient to determine a next Rapamycin dosage;

space="preserve" listing-type="equation">ND=CD-((((CL-DL)/CL)/(1+(CD/30)))/CD)+((0.2×

CD)×

(((1+d)-(1+e))/abs((1+d))))

wherein,

ND=the next RPM dosage,

CD=the patient'"'"'s current RPM dosage,

CL=the patient'"'"'s current RPM whole blood level,

DL=the desired RPM whole blood level for the patient,

RD=the patient'"'"'s previous RPM whole blood level,

e=CL-RD, and

d=DL-RD.

(e) administering a next dose of Rapamycin to the patient in accordance with the next Rapamycin dosage determined from the relationship.

32. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the system to combat infection, comprising the steps of:

(a) administering an initial dose of Cyclosporin to the patient;

(b) examining the patient to determine a current Cyclosporin whole blood level for the patient;

(c) determining a desired Cyclosporin level for the patient;

(d) employing the following relationship along with the patient'"'"'s current Cyclosporin dosage, the patient'"'"'s current Cyclosporin whole blood level, and a potential next Cyclosporin dosage to determine a next Cyclosporin dosage;

space="preserve" listing-type="equation">ND=CD-((((CL-DL)/CL)/(2.5+(CD/1500)×

2.5))/CD)+((0.2×

CD)×

(((1+d)-(1+e))/abs((1+d))))

wherein,

ND=the patient'"'"'s next Cyclosporin dosage,

CD=the patient'"'"'s current Cyclosporin dosage,

CL=the patient'"'"'s current Cyclosporin whole blood level, and

DL=the desired Cyclosporin level for the patient,

RD=the patient'"'"'s previous Cyclosporin whole blood level

e=CL-RD

d=DL-RD

(e) administering a next dose of Cyclosporin to the patient in accordance with the next Cyclosporin dosage determined from the relationship.