PrimeCuts -This Week In The Journals

November 8, 2010

By Verity Schaye, MD and Ishmeal Bradley, MD

Faculty Peer Reviewed

This past week we saw yet another significant election in modern American history. The Republicans, with significant Tea Party support, managed to wrest control of the House from the Democrats, but the Democrats held on strong to the Senate. One of the central issues of this midterm election was health care and the monumental reform that was passed by Democrats earlier this spring. While the voting public emphatically chanted that Congress should repeal the reform, the same people are also quite fond of specifics of the health care law. This political schizophrenia confuses both the newly empowered Republicans and pundits about what the next policy move should be.

This election was also notable for the huge turnout of older voters (and lack of younger voters). Many of these senior citizens were voting out of fears regarding health care, specifically Medicare. This older voting bloc will continue to have a significant impact on elections. Also, as the American population grays, another chronic disease will become more prevalent, Alzheimer disease. In a new study published in JAMA, neurologists examined whether docosahexanoic acid (DHA), an omega-3 fatty acid, would slow the decline of cognitive and functional decline in patients with mild and moderate Alzheimer dementia.[1] They conducted a randomized, double-blind, placebo-controlled trial to test their theory that DHA supplementation would be beneficial. It is known that DHA levels are decreased in the brains of Alzheimer patients, and animal studies have shown that increased intake of DHA can reduce Alzheimer-like pathology in the brain. Using both functional MRI and the Alzheimer’s disease Assessment Scale, the researchers found no difference between the two groups. The study was also hindered because of a relatively large dropout rate (28% in the treatment group, and 24% in the placebo group). The authors attributed this to the participants’ perceived lack of drug efficacy. Although this novel trial did not show a particular benefit in this population, it does provide new research questions for further studies, particularly, would DHA supplementation be beneficial in preventing Alzheimer dementia in patients at high risk for developing the disease.

According to the CDC, chronic lower respiratory diseases are the fourth leading cause of death. Better treatment regimens are currently needed, especially for those of us who treat these patients. Regarding chronic asthma, a mainstay of therapy has been adding a long-acting beta-agonist when patients are not controlled with an inhaled steroid. For our COPD patients, we also use long-acting anticholinergics, like tiotropium. A study based out of North Carolina wanted to test whether the addition of tiotropium to an inhaled glucocorticoid would improve pulmonary function (morning peak flow) and symptoms (number of symptom-free days, number of times rescue inhaler was used, use of health care services, and inflammatory biomarkers).[2] This double-blind, triple-dummy crossover study compared three groups: 1. standard beclomethasone dose, tiotropium, and salmeterol placebo; 2. double the beclomethasone dose, tiotropium, and salmeterol placebo; 3. beclomethosone, tiotropium, and salmeterol. Each group received the assigned therapy for fourteen weeks and was then switched to the next therapy, with a two-week washout period. Their results showed that the addition of tiotropium was superior to doubling the corticosteroid dose in both pulmonary function and symptoms. Furthermore, tiotropium was not inferior to salmeterol, which is the standard step-up therapy. Their small study of 214 patients does provide some evidence for new treatment guidelines, but larger studies with longer follow-up periods should also be conducted.

Furthermore, followers of lung cancer therapies will be excited to know that a new oral chemotherapy drug is in the works. Taking advantage of the fact that some non-small cell lung cancers exhibit a fusion gene with anaplastic lymphoma kinase (ALK), researchers from the Harvard hospitals have created a new antibody against ALK, crizotinib, targeted against this fusion gene.[3] This early phase clinical trial studied 82 patients who had ALK-positive, non-small cell lung cancer and was designed to test for adverse events and response to treatment. After a median treatment duration of 6.4 months, they reported a 57% response rate based on CT and/or PET scans. Thirty-three percent had stable disease. Their work is promising in that it could provide a novel therapy for this specific lung cancer, and it highlights the growing trend in tumor classification and treatment based upon genetic derangements instead of pathology.

Going below the diaphragm for a moment, there may be good news for hepatitis C treatment. Current HCV treatment is interferon-based, but this can be limited by poor patient tolerability. An Australian study tested a new oral treatment regimen consisting of RG7128 (a new nucleoside polymerase inhibitor) and danoprevir (a protease inhibitor) in patients with chronic HCV infection.[4] This randomized, double-blind, placebo-controlled, dose-escalation trial wanted to see if this new regimen, and which doses, was superior to traditional standard of care. They divided 88 patients into ten groups, one of which was the placebo arm. The other nine intervention groups received varying doses of RG7128 (either 500mg or 100mg twice daily) and danoprevir (100mg q8h, 200mg q8h, 600mg twice daily, or 900mg twice daily). Their primary outcome was the change in plasma HCV RNA concentration after two weeks of treatment. They found that an interferon-free regimen could suppress HCV viral level. This could provide a new treatment alternative for these patients. Two important limitations of the study though should be addressed. They excluded cirrhotic patients, so it is unclear if this regimen would help those patients. Also, the short follow-up fails to answer the question of whether this new regimen can maintain, rather than initiate, sustained virologic response. More studies are needed.

As this election season winds down and both parties gear up for a predicted two years of political gridlock, it is comforting to know that progress can still happen. The future may be questionable for the recently enacted health care law, but at least physicians and scientists are making inroads into new treatments for some of our most common chronic diseases.

Dr. Schaye is a third- year resident at NYU Langone Medical Center and Dr. Bradley is a Section Editor, Clinical Correlations.

Faculty peer reviewed by Neil Shapiro, Editor-In-Chief, Clinical Correlations

Image courtesy of Wikimedia Commons.

References:

1.  Quinn, J., et al. Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease. JAMA 2010; 304(17): 1903-1911.  http://jama.ama-assn.org/cgi/reprint/304/17/1903

2.  Peters, S., et al. Tiotropium Bromide Step-Up Therapy for Adults with Uncontrolled Asthma. NEJM. 2010; 363 (18): 1715-1726.  http://www.nejm.org/doi/pdf/10.1056/NEJMoa1008770

3.  Kwak, E., et al. Anaplastic Lymphoma Kinase Inhibition in Non-Small-Cell Lung Cancer. NEJM. 2010; 363 (18): 1693-1703.  http://www.nejm.org/doi/pdf/10.1056/NEJMoa1006448

4.  Gane, E., et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. The Lancet 2010; 376(9751): 1467-1475. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61384-0/fulltext

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