Biomarkers and methods for assessing myocardial infarction and serious infection risk in rheumatoid arthritis patients
AssigneesCrescendo Bioscience, Inc., The UAB Research Foundation
InventorsKerri FORD, Jeffrey R. CURTIS
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Abstract
Provided herein are methods for assessing risk of infection or cardiovascular disease (CVD) in a subject with an inflammatory disease, e.g., rheumatoid arthritis. The methods include performing immunoassays to generate scores based on quantitative data for expression of biomarkers relating to inflammatory biomarkers with or without additional clinical variables to assess infection and CVD risk. Also provided are uses of inflammatory biomarkers for guiding treatment decisions.
Claims21
1-32. (canceled)
A method for treating cardiovascular disease (CVD) or infection in a subject with inflammatory disease, the method comprising:
- performing an immunoassay on a sample from the subject to generate a dataset comprising protein level data for at least two protein markers of the group comprising chitinase 3-like 1 (cartilage glycoprotein-39) (CHI3L1);
- C-reactive protein, pentraxin-related (CRP);
- epidermal growth factor (beta-urogastrone) (EGF);
- interleukin 6 (interferon, beta 2) (IL6);
- leptin (LEP);
- matrix metallopeptidase 1 (interstitial collagenase) (MMP1);
- matrix metallopeptidase 3 (stromelysin 1, progelatinase) (MMP3);
- resistin (RETN);
- serum amyloid A1 (SAA1);
- tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A);
- vascular cell adhesion molecule 1 (VCAM1);
- and, vascular endothelial growth factor A (VEGFA);
- and
- calculating a risk score for the sample indicating CVD or infection present in the subject by combining the dataset with a clinical parameter and a clinical assessment;
- and
- administering a therapeutic regimen to the subject comprising one or more of:
- administering a therapeutic compound selected from a Disease-modifying antirheumatic drug (DMARD), a biologic DMARD, a non-steroidal anti-inflammatory drug (NSAID), and a corticosteroid;
- administering dietary modification and/or supplementation;
- and
- administering bariatric surgical intervention.
The method of claim 1, wherein the at least two protein markers comprise LEP and CRP.
The method of claim 1, wherein the inflammatory disease is rheumatoid arthritis (RA).
The method of claim 1, wherein the infection is associated with inflammatory disease.
The method of claim 1, wherein the infection is a serious infection event.
The method of claim 1, wherein the DMARD is selected from methotrexate (MTX), azathioprine (AZA), bucillamine (BUC), chloroquine (CQ), cyclosporine, doxycycline (DOXY), hydroxychloroquine (HCQ), intramuscular gold (IM gold), leflunomide (LEF), levofloxacin (LEV), sulfasalazine (SSZ), folinic acid, D-pencillamine, gold auranofin, gold aurothioglucose, gold thiomalate, cyclophosphamide, chlorambucil, infliximab, adalimumab, etanercept, golimumab, anakinra, abatacept, rituximab, and tocilizumab.
The method of claim 1, wherein the clinical parameter is selected from age, gender, sex, smoking status, adiposity, body mass index (BMI), and race/ethnicity.
The method of claim 1, further comprising a period of monitoring the subject's symptoms before administering treatment.
The method of claim 1, wherein the clinical assessment is selected from a Disease Activity Score (DAS), a DAS28, a DAS28-CRP, a DAS28-ESR, a Sharp score, a tender joint count (TJC), a swollen joint count (SJC), a Health assessment questionnaire (HAQ), a modified HAQ (mHAQ), a multi-dimensional HAQ (MD HAQ), a visual analog scale (VAS), a physician global assessment VAS, a patient global assessment VAS, a pain VAS, a fatigue VAS, an overall VAS, a sleep VAS, a simplified disease activity index (SDAI), a clinical disease activity index (CDAI), a routine assessment of patient index data (RAPID), a RAPID3, a RAPID4, a RAPID5, an American College of Rheumatology score (ACR), an ACR20, an ACR50, an ACR70, a SF-36, a RA MRI score (RAMRIS), a total Sharp score (TSS), a van der Heijde-modified TSS, a Sharp-van der Heijde score (SHS), a Larsen score, a CRP titer, and an erythrocyte sedimentation rate (ESR).
The method of claim 1, wherein the immunoassay comprises a multiplex assay.
The method of claim 1, wherein the immunoassay comprises:
- obtaining the blood sample, wherein the blood sample comprises the protein markers;
- contacting the blood sample with a plurality of distinct reagents;
- generating a plurality of distinct complexes between the reagents and markers;
- and
- detecting the complexes to generate the data.
The method of claim 1, wherein the calculating a risk score uses a reference group of at least 10,000 patients.
The method of claim 1, wherein the cardiovascular disease is a coronary heart disease (CHD).
The method of claim 1, wherein the risk score is adjusted to a scale of 1-100.
The method of claim 1, further comprising monitoring a response of the subject to a treatment by obtaining one or more additional risk scores for the subject after the treatment.
The method of claim 1, wherein the calculating a risk score uses a statistical tool to derive an interpretation function based on a predictive model of the subject's inflammatory disease.
Dependencies are inferred from the claim text.