Cost utility of tumour necrosis factor-α inhibitors for rheumatoid arthritis: an application of Bayesian methods for evidence synthesis in a Markov model.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 1.5 million people in the US. Tumour necrosis factor (TNF)-α inhibitors have been shown to effectively treat and maintain remission in patients with moderately to severely active RA compared with conventional agents. The high acquisition cost of TNF-α inhibitors prohibits access, which mandates economic investigations into their affordability. The lack of head-to-head comparisons between these agents makes it difficult to determine which agent is the most cost effective. OBJECTIVE: This study aimed to determine which TNF-α inhibitor was the most cost-effective agent for the treatment of moderately to severely active RA from the US healthcare payer's perspective. METHODS: A Markov model was constructed to analyse the cost utility of five TNF-α inhibitors (in combination with methotrexate [+MTX]) versus MTX monotherapy using Bayesian methods for evidence synthesis. The model had a cycle length of 3 months and an overall time horizon of 5 years. Transition probabilities and utility scores were based on published studies. Total direct costs were adjusted to year 2009 $US using the medical component of the Consumer Price Index. All costs and QALYs were discounted at a rate of 3% per year. Patient response to the different strategies was determined by the American College of Rheumatology (ACR)50 criteria. One-way and probabilistic sensitivity analyses (PSAs) were performed to test the robustness of the base-case scenario. The base-case scenario was changed to ACR20 criteria (scenario 1) and ACR70 criteria (scenario 2) to determine the model's robustness. Cost-effectiveness acceptability curves and cost-effectiveness frontiers were used to estimate the cost-effectiveness probability of each treatment strategy. A willingness-to-pay (WTP) threshold was defined as three times the US GDP per capita ($US139,143 per additional QALY gained). Primary results were presented as incremental cost-effective ratios (ICERs). RESULTS: Etanercept+MTX was the most cost-effective treatment strategy in the base-case scenario up to a WTP threshold of $US2 185,497 per QALY gained. At a WTP threshold of greater than $US2 185,497 per QALY gained, certolizumab+MTX was the most cost-effective treatment strategy. One-way analyses showed that the base-case scenario was sensitive to the probability of achieving ACR50 criteria for MTX and each TNF-α inhibitor, and changes in the utility score for patients who achieved the ACR50 criteria. With the exception of infliximab, all of the TNF-α inhibitors were sensitive to drug cost per cycle. In the scenario analyses, certolizumab+MTX was a dominant treatment strategy using ACR20 criteria, but etanercept+MTX was a dominant treatment strategy using ACR70 criteria. CONCLUSIONS: Etanercept+MTX was a cost-effective treatment strategy in the base-case scenario; however, the model was sensitive to parameter uncertainties and ACR response criteria. Although Bayesian methods were used to determine transition probabilities, future studies will need to focus on head-to-head comparisons of multiple TNF-α inhibitors to provide valid comparisons.

Denosumab for treatment of breast cancer bone metastases and beyond.

INTRODUCTION: Bone metastases develop in approximately 70 - 85% of patients with metastatic breast cancer, are incurable and can result in debilitating skeletal complications. Bone-modifying agents to treat breast cancer bone metastases include bisphosphonates. Denosumab is a humanized monoclonal IgG2 antibody targeting receptor activator of NF-κB ligand (RANKL) and provides an alternative therapy for treatment of breast cancer bone metastases. AREAS COVERED: This review provides an overview on denosumab and the RANKL-RANK pathway. Denosumab pharmacokinetics, pharmacodynamics, efficacy, safety and tolerability are discussed. Based on the review of clinical studies, denosumab is efficacious in the treatment of breast cancer bone metastases. Adverse events rates of denosumab are similar to those for bisphosphonates. Preclinical studies have indicated a role of the RANKL-RANK pathway in non-bone-related mechanisms such as mammary gland development and tumorigenesis. EXPERT OPINION: Clinical use of denosumab remains limited and its place in therapy will continue to be defined. Clinical questions, such as the optimal duration of therapy, remain unanswered and need to be addressed.

Thiopurine methyltransferase (TPMT) genotyping to predict myelosuppression risk.

Azathioprine (AZA), 6-mercaptopurine (6-MP), and thioguanine (TG) are thiopurine drugs. These agents are indicated for the treatment of various diseases including hematologic malignancies, inflammatory bowel disease (IBD), rheumatoid arthritis, and as immunosuppressants in solid organ transplants. Thiopurine drugs are metabolized, in part, by thiopurine methyltransferase (TPMT). TPMT displays genetic polymorphism resulting in null or decreased enzyme activity. At least 20 polymorphisms have been identified, of which, TPMT *2, *3A, *3B, *3C, and *4 are the most commonly studied. These polymorphisms have been associated with increased myelosuppression risk. TPMT genotyping may be useful to predict this risk.

Interleukin-28B genotype testing to determine response to the combination of pegylated-interferon and ribavirin for the treatment of hepatitis C virus.

Hepatitis C virus (HCV) is a bloodborne infection that is one of the leading causes of liver disease. If left untreated, HCV can lead to cirrhosis, hepatocellular carcinoma, and death. The current standard of care for HCV is a combination of pegylated-interferon (peg-IFN) and ribavirin (RBV) in which the goal of treatment is to decrease complications and death due to HCV. HCV displays genetic polymorphism, where patients with HCV genotype 1 may have higher viral replication rates and are less likely to respond to treatment. These patients require a longer duration of treatment and a higher RBV dose. The interleukin (IL) 28B genotype test is associated with a sustained virologic response (SVR), defined as an undetectable HCV ribonucleic acid (RNA) upon completion of treatment and 24 weeks thereafter.