Conference Coverage

Generic, brand-name levothyroxine have similar cardiovascular outcomes


AT ATA 2017

– Hypothyroid patients have similar cardiovascular outcomes in the shorter term whether they take generic or brand-name levothyroxine, results of a retrospective propensity-matched cohort study reported at the annual meeting of the American Thyroid Association suggest.

Investigators led by Robert Smallridge, MD, an endocrinologist at the Mayo Clinic, in Jacksonville, Fla., used a large administrative database to study nearly 88,000 treatment-naive hypothyroid patients (most having benign thyroid disease) who started levothyroxine.

Dr. Robert Smallridge of the Mayo Clinic in Jacksonville, Fla. Susan London/Frontline Medical News

Dr. Robert Smallridge

After a median follow-up of about 1 year, those on a brand-name formula and those on a generic formula had similar risks of hospitalization for atrial fibrillation, myocardial infarction, congestive heart failure, and stroke, he reported in a poster session. The findings were essentially the same among the subgroup of older adults, despite their much higher incidences of events.

However, monthly total medication costs with the brand-name medication were more than twice those with the generic.

“I don’t think we are ready yet to say everybody ought to be on generic,” Dr. Smallridge said in an interview, citing the limited treatment duration captured in the study because patients switched medications or changed insurers. “But I think, at least in the short term, it’s giving us some data that we can build upon.”

He and his coinvestigators plan additional analyses looking at longer-term users, other types of thyroid hormone preparations, and the very small group of patients who had thyroid cancer.

“I primarily take care of cancer patients, and we purposely push these patients to slightly lower [thyroid-stimulating hormone levels] in general, which presumably is going to increase your risk of atrial fibrillation and could affect these events,” he said. “The numbers are somewhat smaller, clearly, but I’d like to see that explored also, to see if there is a difference between brand and generics in that subset who are probably getting a little bit more thyroid medication.”

Both hypothyroidism and its overtreatment with thyroid hormone therapy can increase cardiovascular risk, Dr. Smallridge noted.

For the study, the investigators analyzed data from a large administrative claims database (OptumLabs Data Warehouse) for the years 2006-2014. Patients having any prior use of any thyroid hormone preparation, amiodarone, or lithium were excluded. And patients were censored if they left the insurance plan, stopped treatment, or switched medication category.

The investigators identified 201,056 hypothyroid patients who started some type of thyroid hormone therapy. The majority (70.8%) started generic levothyroxine, and 22.1% started brand-name levothyroxine (Synthroid, Levoxyl, Tirosint, Unithroid). The small remaining group started another thyroid extract, triiodothyronine (T3), or a compounded preparation.

Primary care physicians were the main identifiable prescribers (60.3%), followed by endocrinologists (10.8%). “Endocrinologists tended to prescribe brand significantly more than the primary care physicians,” Dr. Smallridge said.

The investigators used propensity matching on a variety of factors (age, sex, race, census region, Charlson comorbidity index, year of index prescription, and a dozen baseline comorbidities) to compare patients starting brand-name versus generic levothyroxine. Outcomes were assessed during a median follow-up of 1 year (range, 0-9.3 years).

Event rates per 1,000 patient-years with branded versus generic levothyroxine were similar for atrial fibrillation (2.19 vs. 1.82; hazard ratio, 1.22, P = .19), myocardial infarction (1.83 vs. 2.12; HR, 0.86, P = .35), and congestive heart failure (2.00 vs. 2.27; HR, 0.88, P = .41). There was a borderline-significant difference on hospitalization for stroke, with marginally lower risk with brand-name levothyroxine (2.38 vs. 3.10; HR, 0.77; P = .05).

Findings were essentially the same in age-stratified analyses, splitting patients into subgroups younger and older than age 65.

When average 30-day costs were compared for users of branded versus generic levothyroxine, total cost for the branded drug was more than twice as high ($18.47 vs. $8.18).

“Thyroid preparations have been the most prescribed drug in the United States for several recent years. In the neighborhood of 25 million different patients a year take thyroid medications,” Dr. Smallridge said. “In terms of the dollars spent, it’s considerably less than some of the other drugs out there. But because of sheer numbers of patients, in terms of impact on health care dollars, it’s still a significant amount of money. And this is a lifelong treatment – once you go on thyroid hormones, you’re on them for life.”

The study had several strengths. “This is a very large, diverse, real-world population across the entire country with a wide range of ages,” Dr. Smallridge explained. “We got pharmacy claims documenting that they were continuing to get the refills, although we didn’t do pill counts, so we don’t know whether they were taking the medication. And a really important thing was the propensity score matching.”

At the same time, limitations included possible variations in coding and billing, and some residual confounding. “Key issues are that we need more data on longer-term follow-up, and we didn’t have lab values,” he added.

Dr. Smallridge reported that he had no relevant conflicts of interest.

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