ti melatonin lady opinioni

The sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin (Farxiga) — despite the cost of the drug being high — is still a cost-effective option compared with standard of care for patients with chronic kidney disease (CKD), at least within the UK, Germany, and Spain, a new analysis shows.

Estimating overall costs of outcomes from the Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial, the authors of the new study found that patients receiving dapagliflozin had delayed CKD progression and reduced hospitalizations due to heart failure compared with those receiving standard of care. They also calculate that these provided important cost offsets to the higher acquisition costs of using the SGLT2 inhibitor. Life expectancy was correspondingly predicted to increase by 1.7 years in those taking dapagliflozin compared with patients receiving standard of care.

“Our results indicate that should patients with CKD be treated with dapagliflozin at an early stage of disease, the rate of cardio-renal complications could be reduced, leading to improved health-related quality of life in patients and significant benefits for healthcare systems in a cost-effective manner,” lead author Phil McEwan, PhD, hydrocodone acetaminophen 5 500 vs oxycodone Cardiff, UK, said in a statement issued by the American Society of Nephrology.

“Our results show that dapagliflozin, added to standard therapy, is a cost-effective treatment option for CKD well below established willingness-to-pay thresholds in the UK, Germany, and Spain,” write McEwan and coauthors in their article, published online in the Clinical Journal of the American Society of Nephrology.

Commenting on the findings in an accompanying editorial, Annika Khine, MD, and Eugene Lin, MD, say the cost-effectiveness of dapagliflozin does depend in part on the background cost of treating patients with CKD overall.

“Although dapagliflozin reduces the need for dialysis, total healthcare expenditures with the drug are more costly for two reasons,” they observe. “First, the drug itself is costly. Second, because dapagliflozin conveys a mortality benefit, overall lifetime healthcare expenditures are higher when patients receive dapagliflozin. It is important, therefore, that the authors included the background cost of standard of care treatment into their model, including dialysis and transplant.”

Ultimately, “SGLT2 inhibitors have consistently demonstrated themselves to be cost-effective in diabetic and nondiabetic CKD,” say Khine of the University of Southern California (USC) Medical Center, Los Angeles, and Lin, also of USC.

But they note that the SGLT2 inhibitors can be expected to remain more expensive in the United States than they are in Europe because of the costly nature of US healthcare.

QALY Gains and Incremental Cost-Effectiveness Ratios

DAPA-CKD randomly assigned 4304 patients with CKD but without diabetes to receive dapagliflozin or placebo. The full study results were published in the New England Journal of Medicine in 2020 and showed that during a median of 2.4 years, treatment with dapagliflozin led to a significant 31% relative reduction compared with placebo in the study’s primary outcome, a composite that included at least a 50% drop in estimated glomerular filtration rate (eGFR) compared with baseline, end-stage kidney disease, kidney transplant, renal death, or cardiovascular death.

As a result of the trial, in April 2021, the US Food and Drug Administration approved dapagliflozin for the additional indication of reducing the risk for kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adult patients with CKD at risk for disease progression.

A second trial with an SGLT2 inhibitor, this time empagliflozin (Jardiance) has also just shown benefit among patients with isolated CKD who did not have diabetes or heart failure in the pivotal EMPA-Kidney trial with more than 6600 patients, as recently reported by Medscape Medical News.

The target population for the new cost-effectiveness analysis of DAPA-CKD was reflective of the patient population in the trial overall — namely, adults with pre-kidney failure with an eGFR of ≥ 25 to ≤ 75 mL/min/1.73m2 and a urine albumin-creatinine ratio (UACR) of ≥ 200 to ≤ 500 mg/g.

“Our analyses considered direct healthcare costs only from payer perspectives in the UK, Germany, and Spain,” McEwan and colleagues explain. In all considered countries, patients treated with additional dapagliflozin had a mean life expectancy of approximately 15.4 years compared with a mean of 13.8 years for those receiving standard therapy alone.

Patients treated with dapagliflozin spent a smaller proportion of their lives with kidney failure (19% vs 21%), spending 1.7 more years in the eGFR range from 15 to 89 mL/min/1.73m2 versus patients treated with placebo.

Treatment with dapagliflozin was also expected to result in 19 fewer hospitalizations for heart failure and 28 fewer episodes of acute decline in kidney function for every 1000 patients treated over a lifetime, translating to cost savings, the investigators add.

It did cost more to add the SGLT2 inhibitor to standard therapy by a substantial amount, however.

For example, in the UK, the additional cost of dapagliflozin was $6822; in Germany, it was $17,671, and in Spain, $11,168. These costs are driven by a combination of increased drug acquisition costs and CKD management costs because of increased life expectancy. However, reduced rates of CKD progression and kidney failure, among other clinical events, provided important cost offsets, as the authors observe.

Looking at quality-adjusted life-years (QALY) gained, treatment with dapagliflozin led to a predicted lifetime incremental QALY gain of 0.82, 1.00, and 0.96 in the UK, Germany, and Spain, respectively.

These gains translated to incremental cost-effectiveness ratios (ICERs) of $8280, $17,623, and $11,687 in the UK, Germany, and Spain, respectively, indicating cost-effectiveness at willingness-to-pay thresholds (UK: $27,510 per QALY; Germany and Spain: $35,503 per QALY).

The ICER is the standard measure of cost-effectiveness in health economics. As the authors also note, empagliflozin has also demonstrated cost-effectiveness in a similar analysis of patient-level data from the EMPA-REG OUTCOME trial in patients with type 2 diabetes.

“Results were consistent across the UK, German, and Spanish healthcare settings and important patient subgroups, and they were primarily driven by attenuating disease progression, thereby delaying initiation of dialysis and kidney transplantation and reducing rates of hospitalization for health failure and death,” the authors conclude.

“Hence, treatment of CKD with dapagliflozin represents a good use of healthcare resources if adopted into clinical practice,” they emphasize.

Dapagliflozin Ends Up Costing More for Younger and Healthier Patients  

In their editorial, Khine and Lin also point out that subgroup analyses done in all three countries suggest dapagliflozin is more expensive in healthier and younger patients. “Unfortunately, this…may cause private payers…and public payers…to preferentially invest in sicker, older patients who are perceived to be less ‘expensive’,” they write.

On the other hand, healthier patients are likely to benefit the most from SGLT2 inhibitor therapy, the editorialists emphasize, prompting them to suggest that policymakers might consider negotiating prices more aggressively for these drugs in order to offset any economic incentive to avoid covering them for younger, healthier patients.

Kline and Lin felt that a “key contribution” of the study is that it covers non-US countries, making the findings even more generalizable.

“This study provides a potential blueprint for how the United States could improve affordability of the SGLT2 inhibitors,” they point out. “The Inflation Reduction Act of 2022…grants Medicare an unprecedented ability to negotiate prescription drug pricing starting in 2026. Although SGLT2 inhibitors are not immediately eligible for price negotiations, the law could set the stage for future policies that could make these high-value drugs more affordable, and thus, more cost-effective.”

“Still, even at their current price, these drugs remain a tremendous bargain for patients,” the editorialists conclude.

McEwan has reported employment with Health Economics and Outcomes Research, Cardiff, UK, which has received fees from AstraZeneca in relation to this study, as well as consultancy agreements with Akebia Therapeutics, AstraZeneca, Bayer, Genmab, Gilead Sciences, Medtelligence, Moderna, Novo Nordisk, RTI Health Solutions, SOBI, the Swedish Institute for Health Economics, Think Research, Third Bridge, Vifor Fresenius Medical Care Renal Pharma, Vifor, and Wickenstones. Lin has reported receiving consulting income from Acumen.

Clin J Am Soc Nephrol. Published online November 2, 2022. Full text, Editorial

For more news, follow Medscape on Facebook, Twitter, Instagram, YouTube, and LinkedIn.

Source: Read Full Article