Clinical Utility and Cost Savings in Predicting Inadequate Response to Anti-TNF Therapies in Rheumatoid Arthritis

Bergman, Martin; Kivitz, Alan; Pappas, Dimitrios A.; Kremer, Joel M.; Zhang, Lixia; Jeter, Anna; Withers, John

doi:10.1007/s40744-020-00226-3

Cited by 20 publications

(13 citation statements)

References 79 publications

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“… 3 This lack of efficacy has many negative downstream consequences, including disease progression, increased disease risks by unnecessary immunomodulatory therapies, and a significant waste of economic resources. 4 Understanding the source of this heterogeneity not only will help to direct patients to the most efficacious therapy, but also could provide insights into new therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

Juliá¹,

Gómez²,

López-Lasanta³

et al. 2022

eBioMedicine

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Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

Juliá¹,

Gómez²,

López-Lasanta³

et al. 2022

eBioMedicine

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“…Since the demand for specific tests aiding therapy decisions is high, different efforts regarding biologic therapy prediction have been made. Most of them though focus on a genomic or proteomic attempt, e.g., [ 16 , 17 , 18 , 19 , 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

IL-10 Induced by mTNF Crosslinking-Mediated Reverse Signaling in a Whole Blood Assay Is Predictive of Response to TNFi Therapy in Rheumatoid Arthritis

Krasselt

Gruz

Pierer

et al. 2022

JPM

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(1) Background: To date, the response of patients with rheumatoid arthritis (RA) to the various biologic DMARD available cannot be predicted due to a lack of reliable biomarkers. Based on our preliminary work on tmTNF reverse signaling, we developed a whole-blood assay measuring tmTNF crosslinking-induced IL-10 production to predict the response to TNF inhibitor (TNFi) therapy. (2) Methods: This prospective study included patients with active RA. Depending on the clinical judgment of the attending rheumatologist, either therapy with a TNF or JAK inhibitor was initiated. Clinical parameters and blood samples were obtained at baseline and after 8 weeks of therapy. The blood samples were collected using a newly developed whole-blood assay based on the principle of tmTNF reverse signalling. Subsequently, IL-10 was measured via enzyme-linked immunosorbent assay (ELISA) technique. (3) Results: 63 patients with RA were enrolled. In fifteen patients, TNFi therapy was initiated, while eight patients started a JAKi treatment. The cross-sectional analysis of all patients showed a positive correlation between tmTNF crosslinking-induced IL-10 and parameters of disease activity (CRP [r = 0.4091, p = 0.0009], DAS28 [r = 0.3303, p = 0.0082]) at baseline. In the TNFi treatment study, IL-10 was found to be significantly higher in EULAR responders than in non-responders (p = 0.0033). After initiation of JAKi treatment, in contrast, IL-10 induction was not linked to response. Longitudinal analysis of the TNFi-treated patients revealed IL-10 to decrease in responders (p = 0.04), but not in non-responders after 8 weeks of therapy. Of importance, the IL-10 production at baseline correlated inversely with TNFi response determined by ΔDAS28 in patients with TNFi treatment (r = −0.5299, p = 0.0422) while no such link was observed under JAKi therapy (p = 0.22). Receiver operation characteristics (ROC) analysis demonstrated a high performance of tmTNF/crosslinking-induced IL-10 in predicting a TNFi therapy response according to the EULAR criteria (AUC = 0.9286, 95% Confidence interval 0.7825–1.000, p = 0.0055). (4) Conclusions: In this pilot investigation, we demonstrated the feasibility of a whole-blood assay measuring tmTNF-induced IL-10 to predict clinical response to TNF inhibitor treatment. This approach might support rheumatologists in their decision for an individually tailored RA therapy.

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“…Strategic approaches need to be in place like changing regulations governing health insurance as well as pharmaceutical companies to overcome the cost challenges involved in bringing PM to deliver improved health outcomes to a broader sector of patients. A recent study showed that stratifying patients according to PM-based approaches could save approximately $7 million in overall healthcare costs per 1,000 patients ( 237 ). In that context, detection of HER2, a validated biomarker in a specific cohort of patients with breast cancer overexpressing HER2 in tumors, reduced the clinical trial risk by 50 and 27% reduction in cost ( 238 ).…”

Section: The Downside Of Pmmentioning

confidence: 99%

Precision Medicine: An Optimal Approach to Patient Care in Renal Cell Carcinoma

et al. 2022

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Renal cell cancer (RCC) is a heterogeneous tumor that shows both intra- and inter-heterogeneity. Heterogeneity is displayed not only in different patients but also among RCC cells in the same tumor, which makes treatment difficult because of varying degrees of responses generated in RCC heterogeneous tumor cells even with targeted treatment. In that context, precision medicine (PM), in terms of individualized treatment catered for a specific patient or groups of patients, can shift the paradigm of treatment in the clinical management of RCC. Recent progress in the biochemical, molecular, and histological characteristics of RCC has thrown light on many deregulated pathways involved in the pathogenesis of RCC. As PM-based therapies are rapidly evolving and few are already in current clinical practice in oncology, one can expect that PM will expand its way toward the robust treatment of patients with RCC. This article provides a comprehensive background on recent strategies and breakthroughs of PM in oncology and provides an overview of the potential applicability of PM in RCC. The article also highlights the drawbacks of PM and provides a holistic approach that goes beyond the involvement of clinicians and encompasses appropriate legislative and administrative care imparted by the healthcare system and insurance providers. It is anticipated that combined efforts from all sectors involved will make PM accessible to RCC and other patients with cancer, making a tremendous positive leap on individualized treatment strategies. This will subsequently enhance the quality of life of patients.

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Clinical Utility and Cost Savings in Predicting Inadequate Response to Anti-TNF Therapies in Rheumatoid Arthritis

Abstract: Introduction: The PrismRA Ò test identifies rheumatoid arthritis (RA) patients who are unlikely to respond to anti-tumor necrosis factor (anti-TNF) therapies. This study evaluated the clinical and financial outcomes of Digital Features To view digital features for this article go to:

Cited by 20 publications

References 79 publications

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

IL-10 Induced by mTNF Crosslinking-Mediated Reverse Signaling in a Whole Blood Assay Is Predictive of Response to TNFi Therapy in Rheumatoid Arthritis

Precision Medicine: An Optimal Approach to Patient Care in Renal Cell Carcinoma

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