Allison Inserro

A recent comparative effectiveness study looked at secukinumab compared with ustekinumab for 

 by emulating a real-world clinical setting.

, found that secukinumab resulted in more patients achieving a Psoriasis Area and Severity Index (PASI) score of 2 or lower after 12 months of therapy compared with ustekinumab.

However, both drugs had lower treatment effectiveness in the simulated real-world clinical setting than in a trial setting, hinting that psoriasis therapies may be less effective than clinical trial data have shown.

The researchers conducted the comparative effectiveness study to overcome some of the limitations of randomized clinical trials (RCTs); they noted, for instance, that head-to-head studies comparing one drug to another are rare in the pharmaceutical industry. In addition, RCTs do not fully reflect real-world outcomes, and evidence of the comparative efficacy of nonbiologic systemic therapies is lacking.

In addition to comparing the 2 therapies, the researchers sought to test whether they could repeat the relative effectiveness estimate of the 

, a randomized clinical trial that compared secukinumab with ustekinumab for psoriasis. That trial found that secukinumab was superior to ustekinumab at week 16 at achieving PASI 90, along with attaining greater improvement in health-related quality of life.

The researchers emulated a trial using data from the 

British Association of Dermatologists Biologics and Immunomodulators Register

 (BADBIR) in an effort to provide treatment effect estimates. BADBIR is an observational, multicenter, longitudinal pharmacovigilance study in the United Kingdom and Ireland that is assessing the safety of biologic treatments for patients with moderate to severe psoriasis. The National Institute for Health and Clinical Excellence has recommended that all UK patients taking biologics for psoriasis join the registry.

The authors wrote that “a target trial emulation approach can provide robust estimates of relative effectiveness that can be used for clinical and regulatory decision-making.” Effectiveness, they wrote, is the performance of a therapy in a clinical setting, while efficacy is how a therapy performs in an ideal setting. Data such as the kind from this observational, emulated trial can help to quantify the gap between efficacy and effectiveness.

Participants had chronic plaque psoriasis, were 18 years or older, and had at least 1 record of a PASI score of 12 or higher before beginning secukinumab or ustekinumab.

The study was performed between November 2007 and August 2019. The primary outcomes were the risk ratio (RR) and the risk difference (RD) for achieving PASI of 2 or lower after 12 months of therapy for secukinumab compared with ustekinumab. The researchers used propensity score (PS) 1:1 matched analysis and inverse probability treatment weighted analysis to account for potential confounding between the 2 groups.

Only eligible participants with no missing baseline data for the potential confounders were included in the final analysis; if outcome data were missing, the outcome was imputed as a nonresponder after 12 months of treatment if the treatment ended before that time point (whether for ineffectiveness or for an adverse event). The outcome was credited as a responder if the treatment was discontinued after 12 months because of disease remission.

A total of 1231 patients were analyzed, with 917 receiving ustekinumab and 314 receiving secukinumab. In all analyses except under the nonresponder imputation method, secukinumab was superior to ustekinumab in the proportion of participants achieving a PASI of 2 or lower (PS-weighted complete case analysis: RR, 1.28; 95% CI, 1.06-1.55; RD, 11.9%; 95% CI, 1.6-22.1).

All analyses reached regulatory agreement in both PS-matching and PS-weighted analyses (except for nonresponder imputation) with the CLEAR RCT. The estimate of the superior effectiveness of secukinumab also met the estimate agreement with the CLEAR trial.

Taking the point estimate from the complete case analysis under PS weighting, the researchers found a 17.5% reduction for secukinumab and a 15.1% reduction for ustekinumab between efficacy and effectiveness using the 12-month end point, with secukinumab having statistically superior effectiveness compared with ustekinumab.

This study was the first to use a target trial approach in comparative effectiveness research of systemic therapies for psoriasis, the authors asserted.

You ZZN, Mason KJ, Hampton PJ, et al. Randomized trial replication using observational data for comparative effectiveness of secukinumab and ustekinumab in psoriasis: A study from the British Association of Dermatologists Biologics and Immunomodulators Register. 

2021;157(1):66-73. doi:10.1001/jamadermatol.2020.4202

Articles

The study sought to understand how psoriasis treatments perform in real-world settings.

Researchers Try to Replicate Secukinumab, Ustekinumab Study With Registry Data

A recent study from Sweden of patients with rheumatoid arthritis (RA) found that when it comes to second-line treatment options such as biologics or Janus kinase inhibitors, most thought that effectiveness, route of administration, or severe side effects are the most important factors to consider.

Patient-centered care has increasingly accepted the view that patient preferences regarding various treatment options are important to take into account and play a role in clinical decision making and regulatory approvals. However, 

 that there is a lack of evidence about the level of side effects patients are willing to accept in second-line treatments.

In this study, patients with RA were recruited through various means to participate in a survey containing demographic and disease-related questions. The survey used a discrete choice experiment, a cross-sectional survey method that assesses preferences in a quantitative way.

Data collection took place between November 2018 to August 2019. Participants were asked to pick their preferred treatment from 2 alternatives.

Out of 422 patients who completed the survey, 358 were included in the final latent class analysis. Most were female (77%) and spanned all age categories between 18 and 80 years.

The medicine with the highest effectiveness

The most important characteristic of treatment cited by patients were the probability of severe side effects, treatment effectiveness, probability of psychological side effects, administration route, frequency of use, probability of mild short-term side effects, and probability of side effects changing appearance, in that order.

Across all participants, treatments with the highest frequency of side effects were strongly disfavored.

However, disease duration influenced the patients’ choices, and those rating treatment effectiveness as the most important attribute were more willing than other participants to accept higher risks of side effects.

The study also measured the minimum acceptable benefit (MAB) levels needed, expressed in percentage point increases in effectiveness, to make up for worsening levels of probability of certain side effects. Due to preference heterogeneity, large differences were found in the MAB across the 3 classes found in the analysis. In class 1, only a small benefit was needed to accept a switch to a less favorable frequency of side effects. Participants in the other 2 classes would require a larger increase in effectiveness to accept an increase in risk of side effects.

The study had some limitations, such as the fact that patients were recruited from multiple sources (RA clinics, a patient organization, and online) so it was not possible to calculate the response rate. But the authors said no duplicates were found in the patient sample. As the study took place in Sweden, the results may not be generalizable to certain other countries with different health systems.

The researchers suggested that future work could include disease activity and risk propensity, which may influence patient preferences, as well as the development of guidelines to include patient preference assessments in regulatory approvals.

Schölin Bywall K, Kihlbom U, Hansson M, et al. Patient preferences on rheumatoid arthritis second-line treatment: a discrete choice experiment of Swedish patients. 

. Published online December 19, 2020. doi: 10.1186/s13075-020-02391-w

Patients with rheumatoid arthritis (RA) were asked their preferences of second-line treatment options such as biologics and Janus kinase inhibitors, taking into account such factors as the probability of severe side effects, treatment effectiveness, administration route, and more.

Study Explores Patient Preferences in Second-Line RA Treatment Options 

After Joe Biden is sworn in Wednesday as president amid unprecedented security, he will sign 15 executive orders aimed at undoing the Trump administration’s policies related to the coronavirus disease 2019 (COVID-19), public health, climate change, and other issues, in some cases instituting new ones, such as a “100 Days Masking Challenge” across the federal government.

As the nation crossed the threshold Tuesday of 400,000 deaths from the pandemic, the Biden transition team said that one of his first actions will be an executive order calling on Americans to do “their patriotic duty” and wear a mask. He will also require masks and physical distancing in all federal buildings, on all federal lands, and by federal employees and contractors.

The Biden administration will also take steps to rejoin the World Health Organization (WHO); on Thursday, Anthony Fauci, MD, the head of the National Institute of Allergy and Infectious Diseases (NIAID), will speak to the executive board of the WHO.

Biden will also restore the National Security Council (NSC) Directorate for Global Health Security and Biodefense, which was created by the Obama administration. The Trump administration dissolved the office in 2018, dispersing staff as part of a wider NSC reorganization

In addition, he will create the position of COVID-19 Response Coordinator, who will report directly to the president; Jeff Zients, who previously served in the Obama administration as director of the National Economic Council, and acting director and deputy director of the Office of Management and Budget, will be responsible for coordinating the federal COVID-19 response.

In the area of climate change, the administration will rejoin the Paris Climate Accord and revoke the approval of the Keystone XL oil pipeline.

When Donald Trump took office 4 years ago, he signed just 1 executive order, which pledged to seek the repeal of the Affordable Care Act. Repeal efforts failed, but the Supreme Court is expected to issue a ruling in a case brought by Texas seeking to overturn the health law before its term ends in June.

In addition to the executive orders, the Biden transition team said there will be a review of all regulations and executive actions from the previous administration “that are deemed damaging to the environment or public health” as well as a directive to federal agencies to “prioritize racial equity and review policies that reenforce systemic racism.”

As the nation crossed the threshold of 400,000 deaths from the pandemic, the Biden transition team said that one of his first actions will be an executive order calling on Americans to do “their patriotic duty” and wear a mask.

Focusing on Public Health, Biden to Seek Change With Numerous Executive Orders 

The United States should start allowing Medicare to negotiate insulin 

, according to a position statement released this week by the Endocrine Society.

The Journal of Clinical Endocrinology & Metabolism

is aimed at drug companies, policymakers, pharmacy benefit managers (PBMs), employers, and others, and calls attention to soaring insulin costs, which were the subject of several Congressional hearings in 2019.

Besides Medicare beneficiaries, insulin costs affect 

 who move off of their parents’ health plan after age 26, those on high-deductible health plans, the uninsured or underinsured, and those with low incomes.

 revealed that insulin prices nearly tripled between 2002 and 2013, jumping from $4.34/mL to $12.92/mL. During the same period, estimated spending for insulin per patient increased from $231 to $736. Another report, in January 2019 from the Health Care Cost Institute, showed that between 2012 and 2016, insulin spending per patient almost doubled, from $2864 to $5705, during the 5-year period.

CMS is prohibited by law  from negotiating directly with pharmaceutical companies over drug prices for Medicare beneficiaries.

The society called on PBMs to create transparent pricing arrangements with manufacturers that do not result in large annual increases in manufacturer list prices and on manufacturers to develop patient assistance programs (PAPs) that are inclusive, accessible, and ending the use of copay savings cards.

For instance, although those without health insurance may be eligible for a manufacturer-sponsored PAP, the statement said the programs are cumbersome to navigate, to the point that some patients run out of insulin.

It also called on employers to limit costs to copays without increasing premiums or deductibles and to choose plans with diabetes in mind. More than 34 million Americans have 

, and another 88 million may be prediabetic, the society said.

The statement also called for greater use of real-time, patient-specific benefit information about medication costs in electronic health records for prescribing clinicians, so that they know what patients will be asked to pay and lower cost alternatives are available. This information is not currently widely available.

For Medicare beneficiaries, the cost depends on whether they are covered by Part D or Part B. Those with Part D coverage without a supplemental plan must pay full price for insulin until they meet their deductible, after which point they will pay coinsurance until meeting their plan’s initial coverage limit for prescription drugs ($4020 in 2020). They then enter the so-called donut hole coverage gap, where they pay full price again until catastrophic coverage begins. This is where patients may decide to ration insulin or go without.

Part B covers costs for patients using insulin via a pump. Without a supplemental coverage plan, patients pay 20% of the average sales price as their copay once their annual deductible is met, the society said. While in the donut hole, they will pay 35% of the plan’s cost for covered brand name prescription drugs until reaching their annual out-of-pocket limit of $5000. Catastrophic coverage will then begin, and the Medicare beneficiary will pay a small coinsurance or copay.

"Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it," Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems in Spokane, Washington, 

. "People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin, resulting in many rationing their medication or skipping lifesaving doses altogether."

The statement is aimed at drug companies, policymakers, pharmacy benefit managers, employers, and others, and calls to attention soaring insulin costs, which were the subject of several Congressional hearings in 2019.

Allison Inserro

Articles

Researchers Try to Replicate Secukinumab, Ustekinumab Study With Registry Data

Study Explores Patient Preferences in Second-Line RA Treatment Options

Focusing on Public Health, Biden to Seek Change With Numerous Executive Orders

Endocrine Society Calls for Negotiated Insulin Prices in Medicare