Mark Fuerst

Despite conflicting guidelines on how to treat hypothyroidism, U.S. physicians prescribe combination therapy-adding synthetic liothyronine (LT3) to standard therapy with synthetic levothyroxine (LT4) replacement-more often than physicians around the world.

Both physician characteristics and patient characteristics profoundly affect physician prescribing patterns, according to two new surveys.

The results of this 2017 survey suggest that “approximately one-third of physicians taking care of patients with hypothyroidism are willing to prescribe therapies other than levothyroxine (LT4),” stated the authors, led by Jacqueline Jonklaas, M.D., Ph.D., of Georgetown University Medical Center, Washington, D.C.

In 2012 and 2014, the American Thyroid Association (ATA) guidelines for the treatment of hypothyroidism stated there was insufficient evidence to support routine prescribing of T3-containing therapies. More recent recommendations from British and Italian societies suggest that T3-containing therapies can be considered.

In the 2017 physician survey, ATA members were presented with 13 different theoretical patients with hypothyroidism and asked to choose among six therapeutic options, including levothyroxine, synthetic combination therapy, thyroid extract, and liothyronine monotherapy. The 13 patient scenarios incorporated parameters that provided potential reasons for considering combination therapy, for example, presence of symptoms, low serum triiodothyronine concentration, and documentation of deiodinase polymorphisms.

Of the 389 survey respondents, 93% prescribed therapy for hypothyroidism. About half (53%) of respondents had been in practice for more than 20 years, and about one-quarter (23%) had been in practice for 11 to 20 years. Two thirds (64%) practiced in North America and 18% practiced in Europe; 85% were endocrinologists and 5% were surgeons.

In multivariate analysis looking at the characteristics of physicians published online Dec. 17, 2018 in 

, physicians from North America were both more likely to prescribe any triiodothyronine-containing therapies and more likely to add liothyronine to levothyroxine therapy. In addition, they were more likely to prescribe desiccated thyroid extract or liothyronine monotherapy.

“The current multivariate analysis shows that physician characteristics affect prescribing patterns,” stated the authors.

They suggested this may be due to the impact upon physicians of patient-related experiences, media exposure, influence from pharmaceutical companies, educational activities, or other concerns. “These results have potential importance for understanding physician–patient interactions at a time when the benefits and risks of triiodothyronine-containing therapies have not been fully documented,” they stated.

In an earlier analysis looking at patient characteristics associated with prescription of combination therapy, published online Nov. 12, 2018 in 

, the authors stated that “most endocrinologists encounter patients who are dissatisfied with their current hypothyroidism therapy and request combination therapy with either liothyronine (LT3) or thyroid extract.”

They reported that key significant factors were patients’ symptoms, T3 levels, 

 presence of a polymorphism, and the patient's request for T3 therapy.

The authors concluded “this analysis appears to show a marked increase in the willingness of physicians to prescribe combination therapy in specific circumstances. If current prescribing patterns do incorporate the use of therapies other than LT4, there is a critical need for more research into the benefits and risks of these therapies.”


	Jacqueline Jonklaas, Eshetu Tefera and Nawar Shara. "Prescribing Therapy for Hypothyroidism: Influence of Physician Characteristics," 

. Jan. 23, 2019. https://doi.org/10.1089/thy.2018.0369
	 

Articles

Despite conflicting guidelines on how to treat hypothyroidism, U.S. physicians prescribe combination therapy more often than physicians around the world.

Physician–patient interaction may influence prescribing patterns in hypothyroidism

Patients with hepatitis C virus (HCV)-related cirrhosis who are coinfected with human immunodeficiency virus (HIV), show similar improvements in liver function after achieving undetectable serologic viral response for 12 or more weeks after the end of treatment (SVR12).

The first study to provide comparative results of liver function changes after response to direct-acting antiviral (DAAs) agents between patients with and without HIV infection in a large cohort shows liver function improved in more than half of patients in each cohort.

“From the start of DAA treatment to the date of SVR12 achievement, HIV/HCV-coinfected and HCV-monoinfected patients with cirrhosis show similar rates of recovery in liver function parameters,” stated the researchers, led by Juan Macias of the Infectious Diseases and Microbiology Unit of the Hospital University of Valme in Seville, Spain. “In addition, the frequencies of overall liver function, as measured by Child-Pugh-Turcotte (CPT) and MELD scores as well as by clinical outcome, improvement, and worsening after responding to DAA therapy are similar in patients with HCV-related cirrhosis with and without HIV coinfection.”

The researchers published their results in the January 2019 issue of 

Advanced fibrosis and cirrhosis are more frequent among HIV/HCV-coinfected patients than among HCV-monoinfected patients, and liver decompensation and poor overall survival are more common in coinfected patients. 

Dr. Macia and colleagues compared the changes in several markers of liver function between HCV-monoinfected and HIV/HCV-coinfected patients with cirrhosis who achieved SVR12 to all-oral DAA combinations. The retrospective cohort study included 490 patients, 270 (55%) of them coinfected with HIV and 220 (45%) of them monoinfected with HCV. The DAA regimen was decided taking into account availability of DAA, concomitant medications and comorbidities, and guidelines in force. HIV-coinfected patients receiving atazanavir as a part of their antiretroviral therapy at baseline, before starting DAA, or during anti-HCV treatment, were excluded.

Liver function improved in 50 (56%) HCV-infected patients and in 82 (57%) HIV/HCV-coinfected patients.  Liver function worsened in 33 (15%) HCV-monoinfected patients and in 33 (13%) HIV/HCV-coinfected patients.

Factors independently related with liver function improvement were male gender, bilirubin less than 1.2 mg/dL, and INR less than 1.3 at baseline. After multivariate analysis, albumin less than 3.5 g/dL was associated with liver function worsening.

“HIV status did not influence the likelihood of liver function decline or improvement after adjusting for other baseline predictors,” stated the researchers. “As a consequence, the hypothesized poorer recovery of liver function at SVR12 associated with HIV coinfection was not confirmed.”  Longer follow-up would determine whether this translates into a long-term benefit in the rate of liver events, they added.

In conclusion, the researchers stated: “Available all-oral DAA combinations have allowed the extension of treatment to a diversity of vulnerable patients, including HIV/HCV-coinfected patients. We found that patients with HIV infection and HCV-related cirrhosis show similar improvements in liver function scores after SVR. However, patients with cirrhosis reaching SVR may still be at risk of decompensations. Early improvements in liver function should mean a lower likelihood of liver events, leaving aside the problem of hepatocellular carcinoma.”

MacÃ­as J, Granados R, TÃ©llez F, et al. "Similar recovery of liver function after response to all-oral HCV therapy in patients with cirrhosis with and without HIV coinfection," 

. ePub Sept. 27, 2018. DOI:10.1111/jvh.12990

Advanced hepatitis C virus patients with HIV infection recover liver function with all-oral direct‐acting antivirals (DAA) therapy, study shows.

Mark Fuerst

Articles

Physician–patient interaction may influence prescribing patterns in hypothyroidism

Restoring Liver Function with Oral Therapy