The following summaries represent a small sample of real-world, evidence-based information presented at AMCP Nexus 2017, October 16-19, 2017, in Dallas, TX.
- New Approaches Needed to Address Medication Adherence in Chronic Diseases
- Long-Acting Injectable Antipsychotics Better than Oral Agents in Improving Adherence, Reducing Healthcare Utilization in Patients with Schizophrenia
- Adding Telotristat Ethyl to a Health Plan Formulary Has Minimal Budget Impact
New Approaches Needed to Address Medication Adherence in Chronic Diseases
Patients with chronic diseases, such as type 2 diabetes, hyperlipidemia, or hypertension, have to take their medications long-term to maintain control of their chronic condition. However, medication adherence and persistence are suboptimal in these patients, resulting in poor patient outcomes. At the 2017 Academy of Managed Care Pharmacy (AMCP) Nexus conference, Steven V. Edelman, MD, Clinical Professor of Medicine, University of California San Diego, Veterans Affairs Medical Center, CA, and John E. Anderson, MD, Internal Medicine and Diabetes, The Frist Clinic, Nashville, TN, discussed issues related to medication adherence and persistence in patients with chronic conditions, with a focus on type 2 diabetes, and the need for innovation to improve outcomes.
Data from Medicaid and HEDIS show that the percentage of patients with hemoglobin (Hb)A1c levels <7% has not changed in the past 10 years, Dr Edelman said, despite advances in therapies and new delivery technologies, which is largely attributed to poor medication adherence.
Medication adherence is typically defined by the proportion of days covered and medication possession ratio (MPR). If the MPR is 80%, patients are considered adherent. This means that patients can miss up to 20% of their doses and still be considered adherent. But MPR does not confirm that the patient is actually taking the medication but only that the patient has the drug. Patients, especially those who cannot afford their medications, may choose to stockpile medications and not take them. MPR does not account for what the patient actually takes.
“It turns out that the numbers that you see on adherence are probably way off, that there are many more people who are poorly adherent than there are adherent,” Dr Edelman said.
Another issue is persistence, which is how long a patient is taking the medication. Unlike type 1 diabetes, type 2 diabetes is considered a “silent” condition, and people do not feel different whether they take the medication or not. Therefore, patients with type 2 diabetes have no urgency to take their medications, such as insulin, glucagon-like peptide (GLP)-1 receptor agonists, or dipeptidyl peptidase (DPP)-4 inhibitors, especially considering the associated costs and the fear of side effects.
“This issue of adherence is going to be the single biggest problem in chronic disease states, especially type 2 diabetes,” said Dr Edelman. “When you look at study after study on adherence and persistence, about 25% to 30% of patients are still on that medication after 1 year, and even lower after 2 years, whether you are talking about an injectable agent, a basal insulin, or GLP 1 agent, or even oral DPP 4 medication.”
And this low rate is true even for drugs with no or minimal side effects, such as once-daily DPP-4 inhibitors.1 Medication persistence is also poor among patients with chronic conditions; fewer than 40% of patients are still taking their medication after 2 years, regardless of the condition.2 According to 2017 data, for every 100 prescriptions written, only 50% to 70% are relayed to the pharmacy, 48% to 66% are picked up, 25% to 30% are taken as instructed, and only 15% to 20% are actually refilled.3
Nonadherence is also costly. “There is a strong relationship between adherence and how much a patient costs the system,” Dr Edelman said. “When people are poorly adherent, it costs the system a lot of money. It’s amazing how much money the healthcare system can save when patients are adherent and persistent with their medications.” He cited data showing that in a group of patients with type 2 diabetes, poor adherence translated to increased risk for hospitalization and all-cause mortality.4 Conversely, every 1% improvement in drug utilization is associated with approximately a 1% drop in the cost of care, and every 1% increase in adherence is linked to a 0.1% decrease in HbA1c levels.5
Of note, drug approval is based on data from clinical trials, but clinical trials rarely translate to everyday practice. Patients who participate in randomized clinical trials get the “Cadillac” treatment, Dr Edelman suggests; they receive extra support and attention, such as additional provider visits, frequent monitoring and follow-up, and access to educational resources, which can encourage patients to take their medication during the study, which is a finite period, whereas in the real world, patients with chronic diseases have to take the drug forever.
Dr Edelman and colleagues studied the gap between clinical trial and real-world results in patients with type 2 diabetes who used GLP-1 receptor agonists, comparing results from 11 randomized, phase 3 studies of GLP-1 receptor agonists and DPP-4 inhibitors versus real-world data from the Optum/Humedica database of patients with similar characteristics.6 At the end of 1 year, the efficacy seen with GLP-1 receptor agonists in reducing HbA1c levels in the real world was less than half that seen in clinical trials. Multiple regression analyses showed that 75% of this efficacy gap was caused by medication adherence.6
“We have to do a lot more to help our folks with type 2 diabetes to be more adherent. I personally think it’s a combination of technology, better medications that are easy to take, that lead to a greater adherence.”
Medication adherence is a multifactorial issue, with system- and patient-related barriers, said Dr Anderson. These include forgetting to take the medication; difficulty opening, and/or reading, the medication bottle; unwillingness to take the drug because of side effects; and financial challenges. So—“What are the solutions?” he asked.
Traditional approaches to improving medication adherence in type 2 diabetes include fixed-dose combination therapies, long-acting injections, pen technology, software and reminder technologies, and disease management programs. But real-world outcomes remain suboptimal, because these strategies do not address all the barriers together.
“If you’re going to take a systematic approach to try and improve adherence, you can’t just target one of these. You’re going to have to have a multifactorial approach,” Dr Anderson said.
A wide array of technology-based approaches are emerging to improve adherence. Bottle cap sensors technology reminds the patient to take the medicine, and it tracks adherence, but it does not address refill issues, cost, and other issues related to adherence. Weight-based sensors technology can detect if the bottle was opened and drug was taken out, and provides alerts to the clinician, but it does not guarantee that the patient is actually taking the medication, and most providers will not spend the time to monitor it. Chip-in-the-pill technology can detect if the medication was administered and is in the body, but it does not address tolerability issues. Camera-based technology can detect if the drug was ingested in real time via a smartphone camera, but adherence relies on a busy physician to monitor this technology.
Finally, implantable delivery systems extend the period of medication delivery for several months, without involving the patient; so when used with a medication with no side effects, it can be a promising approach. This system does require an office visit every several months to administer the medication, but it does address many of the adherence barriers: it is administered by a physician (thereby ensuring the medicine is being taken); remembering to take it is not an issue; and unless patients return to the physician’s office to remove the device, they will continue to receive medication. However, financial barriers remain.
Artificial pancreas technology leverages a paired continuous glucose meter and insulin pump to monitor glucose levels in real time and adjusts the rate of insulin administration. This technology, too, addresses the majority of the barriers to medication adherence.
Implantable technology for type 2 diabetes is still investigational, Dr Anderson said, noting that its advantage is that it provides “continuous delivery of medication.” He added that advanced technology approaches have shown promise in small patient populations, but need to be studied in the real world to better understand the impact on patient outcomes. He commented that health plans are actively evaluating innovative adherence technologies, but few are providing reimbursement for them, leaving plan members uncovered for these new technologies, which limits the amount of real-world evidence that can be generated.
“We need some real-world data so that we can focus on the ones [technologies] that actually work and make a difference in our patients. If we’re going to generate it, it’s important that payers are going to have to play some role in helping us get that evidence,” concluded Dr Anderson.
1. Briesacher BA, Andrade SE, Fouayzi H, Chan KA. Comparison of drug adherence rates among patients with seven different medical conditions. Pharmacotherapy. 2008;28:437-443.
2. Yeaw J, Benner JS, Walt JG, et al. Comparing adherence and persistence across 6 chronic medication classes. J Manag Care Pharm. 2009;15:728-740.
3. National Association of Chain Drug Stores. Pharmacies: improving health, reducing costs. www.nacds.org/pdfs/pr/2011/PrinciplesOfHealthcare.pdf. Accessed November 27, 2017.
4. Ho PM, Rumsfeld JS, Masoudi FA, et al. Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus. Arch Intern Med. 2006;166:1836-1841.
5. Roebuck MC. Medical cost offsets from prescription drug utilization among Medicare beneficiaries. J Manag Care Pharm. 2014;20:994-995.
6. Carls GS, Tuttle E, Tan RD, et al. Understanding the gap between efficacy in randomized controlled trials and effectiveness in real-world use of GLP-1 RA and DPP-4 therapies in patients with type 2 diabetes. Diabetes Care. 2017;40:1469-1478.
[Source: Edelman S, Anderson J. Innovative approaches to improving medication adherence in chronic diseases: insights from real-world outcomes.]
Long-Acting Injectable Antipsychotics Better than Oral Agents in Improving Adherence, Reducing Healthcare Utilization in Patients with Schizophrenia
Studies suggest that long-acting injectable antipsychotics improve adherence and reduce healthcare utilization compared with oral agents in patients with schizophrenia, but this has not been investigated in the real-world setting.
Shah and colleagues used real-world data from the Truven Health MarketScan Multi-State Medicaid database to compare healthcare utilization, treatment patterns, and costs for patients with schizophrenia who used either long-acting injectables or long-acting oral antipsychotics between January 1, 2011, and December 31, 2014. Outcomes were assessed 12 months after the date of the first prescription for an antipsychotic drug in 22,490 eligible patients. Of these patients, 12.9% received injectable antipsychotics and 87.1% received oral antipsychotics. After a propensity-score matching, 2302 patients were included in each cohort, which were balanced in terms of baseline characteristics and proportion of days covered for their medications.
The results showed that patients who used injectable agents were significantly less likely (30.8%) to discontinue treatment than those using oral antipsychotics (45.3%); had fewer inpatient admissions (0.5 vs 0.9, respectively), hospitalization days (3.9 vs 6.5), and emergency department visits (2.4 vs 2.9; all P <.01). Conversely, those using injectable drugs had more prescriptions filled than those using oral agents (29.5 vs 25.3; P <.01).
In addition, the overall healthcare costs were similar in the 2 cohorts, but the monthly drug costs were $505 higher among those using injectable antipsychotics than those using oral drugs. However, this difference was offset by significant, $397 lower monthly inpatient costs and $17 lower emergency department costs than for those using oral antipsychotics (P <.01).
“The discontinuation rate differences may account for reduced inpatient admissions. Hospital bed-day cost reductions offset the higher costs of LAI [long-acting injectable] medications, thereby resulting in no increase in total health care costs relative to oral antipsychotics over 12 months,” concluded Shah and colleagues.[Source: Shah A, Xie L, Kariburyo F, et al. Real-world comparison of treatment patterns, health care resource utilization, and costs in schizophrenia patients treated with long-acting injectable versus oral antipsychotics.]
Adding Telotristat Ethyl to a Health Plan Formulary Has Minimal Budget Impact
Carcinoid syndrome is associated with neuroendocrine tumors of the lung or gastrointestinal tract origin; diarrhea is among the most common symptoms of carcinoid syndrome. The syndrome affects <1% of the US population, and in approximately 40% of the patients with carcinoid syndrome diarrhea, somatostatin analog monotherapy does not control the syndrome. Telotristat ethyl has been approved by the US Food and Drug Administration in 2016 for use, in combination with a somatostatin analog, for the treatment of patients with carcinoid syndrome diarrhea that is not controlled with a somatostatin analog alone.
Kohli and colleagues performed an economic analysis using a Markov model to assess the potential 3-year impact on the annual budget of a hypothetical health plan with 10 million members of adding telotristat ethyl, in combination with somatostatin analog octreotide LAR, to the formulary. The investigators calculated the monthly drug costs of octreotide LAR and telotristat ethyl and the per-member per-month (PMPM) costs.
The analysis showed that reimbursing for telotristat ethyl in addition to the somatostatin analog resulted in a cost of $1,474,000 in year 1; $1,837,000 in year 2; and $2,312,000 in year 3. The PMPM cost was $0.01 in year 1, $0.02 in year 2, and $0.02 in year 3.
These results suggest that reimbursing for the use of telotristat ethyl as part of a combination with a somatostatin analog for appropriate patients would have a minimal impact on a health plan budget, according to the investigators.
[Source: Kohli M, Maschio M, Joish V, et al. Budget impact of telotristat ethyl in the treatment of patients with uncontrolled carcinoid syndrome.]