Prediction of therapeutic response in inflammatory conditions
Response to treatment of an inflammatory condition can be predicted based on characteristics of one or more markers from a subject. The markers can include expressions of nucleotide sequences identified herein and of combinations thereof. A response value can be calculated based on characteristics (e.g., expression levels) of one or more of the markers, as well as other characteristics of the subject, such as baseline clinical data. The treatment can be administered when the response value is beyond a threshold.
1. A method of treatment, comprising:
measurinq, from a sample of a subject prior to administration of a TNF inhibitor treatment to the subject, (a) an amount of an mRNA sequence corresponding to SEQ ID NO:1, present in the sample; and (b) an amount of an mRNA sequence comprising SEQ ID NO:2, present in the sample;
diagnosing the subject as a responsive subject when the subject, prior to administration of the TNF inhibitor treatment, has a response value substantially equivalent to the final r[00] calculated in the sequence of operations below and beyond a threshold:
1 r[02]=ADD(r[5], 2)
2 r[00]=ADD(r[6], 1)
3 r[00]=DIV(r[2], r[0])
4 r[01]=SIN(r[6])
5 r[00]=SUB(r[0], r[1])
6 r[02]=MOD(r[1], r[0])
7 r[03]=MOD(5, r[0])
8 r[00]=SIN(r[0])
9 r[00]=ADD(r[2], r[0])
10 r[03]=MUL(r[3], r[3])
11 r[02]=ADD(r[6], r[3])
12 r[03]=DIV(r[3], r[2])
13 r[00]=ADD(r[3], r[0])
14 r[00]=ADD(r[3], r[0])
wherein:
r[5] is a normalized value of the amount of the mRNA sequence corresponding to SEQ ID NO:1; and
r[6] is a normalized value of the amount of the mRNA sequence corresponding to SEQ ID NO:2; and
after the diagnosing, administering to the responsive subject the TNF inhibitor treatment, comprising administration of an effective amount of a medicament comprising a TNF inhibitor.
2. The method of claim 1 , wherein after the administering, the responsive subject has a decrease in a DAS28 score.
3. The method of claim 1 , further comprising: not administering the medicament to the subject, within one month of the diagnosing, when the response value is not beyond the threshold.
4. The method of claim 1 , wherein the medicament comprises infliximab, adalimumab, leflunomide, anakinra, azathioprine, cyclophosphamide, and/or etanercept.
5. The method of claim 1 , wherein the medicament comprises an anti-inflammatory agent.
6. The method of claim 1 , wherein the medicament comprises a monoclonal antibody.
7. The method of claim 1 , wherein the responsive subject has a decrease in DAS28 score within a 14 week period after administering the medicament.
8. The method of claim 1 , wherein the responsive subject has a decrease in DAS28 score by 1.2 or more within a 14 week period after commencing administering the medicament.
9. The method of claim 1 , wherein the threshold is 0 or a value between a first value and a second value, wherein the first value is a mean of sample response values of a first one or more sample subjects who respond to an anti-TNF treatment, and the second value is a mean of sample response values of a second one or more subjects who do not respond to the anti-TNF treatment, and wherein the sample response values for each of the sample subjects is determined based on the amount of an mRNA sequence corresponding to SEQ ID NO:1, present in the sample; and the amount of an mRNA sequence comprising SEQ ID NO:2, present in the sample.
10. A method of treatment, comprising:
measuring, from a sample of a subject prior to administration of a TNF inhibitor treatment to the subject, (a) an amount of an mRNA sequence corresponding to SEQ ID NO:1, present in the sample; and (b) an amount of an mRNA sequence comprising SEQ ID NO:2, present in the sample;
diagnosing the subject to be a responsive subject when the subject, prior to administration of the TNF inhibitor treatment to the subject, has a response value substantially equivalent to the final r[00] calculated in the sequence of operations below and beyond a threshold:
1 r[06]=MUL(r[12], 2)
2 r[07]=MUL(r[14], 7)
3 r[07]=SUB(11, r[7])
4 r[06]=SUB(r[6], r[7])
5 r[00]=DIV(5, r[6])
6 r[05]=SUB(r[14], r[7])
7 r[02]=DIV(r[13], r[5])
8 r[07]=SUB(r[13], r[7])
9 r[00]=ADD(r[2], r[0])
10 r[05]=SUB(r[14], r[7])
11 r[02]=DIV(2, r[5])
12 r[00]=ADD(r[2], r[0])
wherein:
r[12]=Treatment_num, wherein Treatment_num=1 if the subject is administered a drug, Treatment_num=0 if the subject is administered a placebo;
r[14] is a normalized value of the amount of the mRNA sequence corresponding to SEQ ID NO:1);
r[13] is a normalized value of the amount of the mRNA sequence corresponding to SEQ ID NO:2; and
after the diagnosing, administering to the responsive subject the TNF inhibitor treatment, comprising administration of an effective amount of a medicament comprising a TNF inhibitor.
11. A method of treatment, comprising:
measuring, from a sample of a subject prior to a TNF inhibitor treatment, (a) an amount of an mRNA sequence corresponding to SEQ ID NO:1, present in the sample; and (b) an amount of an mRNA sequence comprising SEQ ID NO:2, present in the sample;
diagnosing the subject to be a responsive subject when the subject, prior to the TNF inhibitor treatment, has a response value substantially equivalent to the final r[00] calculated in the sequence of operations below and beyond a threshold:
1. r[03]=DIV(r[6], 5)
2. r[02]=MOD(7, r[3])
3. r[01]=ADD(r[3], r[2])
4. r[03]=SUB(r[6], r[2])
5. r[02]=POW(r[6], r[1])
6. r[03]=ADD(r[5], r[3])
7. r[00]=MOD(r[3], r[2])
8. r[00]=SUB(r[1], r[0])
wherein:
r[6] is a normalized value of the amount of the mRNA sequence corresponding to SEQ ID NO:1;
and
r[5] is a normalized value of the amount of the mRNA sequence corresponding to SEQ ID NO:2; and
administering to the responsive subject the TNF inhibitor treatment, wherein the TNF inhibitor treatment comprises administration to the responsive subject an effective amount of a medicament comprising a TNF inhibitor.