By Erica Lessem
This summer, Treatment Action Group (TAG) and its partners in fighting tuberculosis (TB) issued a call for zero TB deaths, zero new TB infections, and zero suffering from TB.
Yet the U.S., long a leader in TB elimination efforts, is in jeopardy of losing ground in the struggle to get to zero. Drug shortages, coupled with financial obstacles, are threatening the success of TB programs nationwide. TB, long forgotten by the general public and by many policy makers, still affects the U.S., with over 10,000 new cases in 2011.
The number of people infected with TB bacteria but not yet sick is even greater, amounting to almost 11 million, according to estimates from the U.S. Centers for Disease Control and Prevention (CDC). There is safe and effective therapy to prevent latent infection from developing into active TB disease. In fact, in 2011 the CDC approved a new therapy that shortened the prevention regimen from nine months of daily isoniazid (a common anti-TB drug) to just twelve once-weekly doses of isoniazid and another anti-TB drug, rifapentine. This dramatic advance could spare patients time and literally hundreds of pills. Currently, an estimated 300,000 to 400,000 people have begun treatment for latent TB in the U.S., but many do not complete it—remaining at risk of developing active TB. Many more may be eligible to begin treatment, but do not know they are infected, or are unwilling to take nine months of medication for an asymptomatic infection. The simplified 12-dose regimen may encourage more people with latent TB infection to initiate and complete therapy.
Although the shorter-course regimen offers many advantages, health departments face a huge barrier to implementation: the cost of rifapentine. Even the New York City Department of Health and Mental Hygiene, which houses one of the U.S.’s premiere TB programs, can’t afford to implement rollout of the new preventive treatment. Rifapentine, produced by Sanofi-Aventis under the name Priftin, is available to public TB centers under recently reduced federal discounted pricing; however, the per-patient cost of rifapentine is still $115.88, over ten times more than that of isoniazid. Though rifapentine received approval in 1998 and is no longer under patent, there are no generics available. In New York City, where over 3,500 patients with latent TB infection per year are eligible to receive the new regimen in its public clinics, the drug costs alone would be over $443,380, instead of just over $100,000 in total costs for the nine months of isoniazid alone. As the City, like others around the country, faces federal and local budget cuts (described in further detail below), it cannot spend hundreds of thousands of dollars more per year to implement the new therapy, despite a belief that it would improve treatment-initiation and -completion rates.
Drug pricing also endangers the treatment of active TB disease, especially drug-resistant cases. TB programs in the U.S. identified cost as a leading challenge to obtaining medications for multidrug-resistant TB. The average total cost to treat just one person with multidrug-resistant TB in the U.S. is between $500,000 and $1.8 million. The price of capreomycin, a crucial injectable agent used for at least six months in the treatment of multidrug-resistant TB, just doubled because of a change in manufacturers.
In addition to rising costs, drug supply issues are imperiling TB programs. The U.S. experienced a record number of drug shortages in 2010—a threefold increase over 2005 shortages. The limited availability of antibiotics and injectables, cornerstones of the treatment for drug-resistant TB, is particularly problematic. Recently, only two of four anti-TB injectables used to treat drug-resistant TB have been available, and only so on an emergency basis.
The causes of these drug stock-outs are varied. Often, there is a sole-source provider for second-line drugs, making procurement difficult and unstable. There are shortages of the active pharmaceuticals themselves (this has also been a problem for the first-line drug isoniazid: the main manufacturing plant in the world for the active ingredient in isoniazid was destroyed in the 2011 earthquake and tsunami in Japan). There are delays in manufacturing and shipping, and because many drugs or materials expire quickly, inventory is not kept stocked. Injectables in particular have been found to be contaminated due to unsuitable manufacturing conditions. At times, manufacturers also decide to discontinue products, perceiving the market size or anticipated profits to be small. Finally, some drugs are available only on an investigational-use basis, requiring a long, complex application process to permit their use for TB patients.
These medication shortages are dangerous. They can result in treatment delay, endangering critically ill patients and allowing people with TB to be infectious longer and have more opportunity to transmit the disease. Shortages can also lead to the use of inappropriate treatment regimens or to treatment lapse or interruption, putting patients at risk of side effects or of developing resistance to even more drugs. These shortages also place a huge burden on TB program staff, who have to dedicate excess time to drug procurement.
Given the dual threats of rising costs and shortages of TB drugs, there could not be a worse time for cuts to TB program budgets. Yet city and state TB programs are facing funding shortfalls from the local, state, and federal levels. New York City’s TB program, for example, will have its federal funding slashed by $2 million in 2013, on top of a $300,000 rescission from 2012 and a 10–12% cut in City funding for the next year. A grim warning of the potential results of these and similarly shortsighted budget cuts can be found in the devastating outbreak of multidrug-resistant TB in New York City in the 1990s, which was estimated to have cost at least $1 billion to control. Similarly, over 52,000 excess cases are estimated to have occurred nationwide between 1985–1992, due in part to limited funding for TB in the preceding years.
The U.S. has made enormous progress in the fight against TB, both within and outside of its borders. Yet the country is in jeopardy of falling prey to what the CDC has titled “the low incidence paradox”—the perception that public support to fight TB is no longer necessary, which weakens programs and ultimately leads to an increase in TB. To protect its people and continue to set a global example, the U.S. has a responsibility to maintain and increase its investment in TB programming, and to avoid drug shortages. The CDC and the U.S. Food and Drug Administration (FDA) are making strides toward working with global institutions (such as the Global Drug Facility) to stabilize procurement, and toward helping programs more easily obtain potentially lifesaving second-line drugs.
We can reach zero TB deaths, zero new TB infections, and zero suffering from TB in the U.S., but only if we change the status quo. We are in danger of a reversal in our progress, and we need firm commitments from legislators to maintain (or better yet, increase) funding for TB. Additionally, private-sector commitment, including that of Sanofi-Aventis, to affordable pricing and stable supply of TB drugs is necessary. With political will and private-sector cooperation, our “zero” aspirations can be realized.