PDSA E-News: January 25, 2017




High-dose Dexamethasone Works as Well as Prednisone but More Quickly for Patients with Untreated Primary ITP

Lancet Haematology logoCurrent ITP treatment guidelines recommend either high-dose dexamethasone or standard-dose prednisone as first-line treatment for ITP. There is debate about which dosage to use. High-dose dexamethasone is given as a short pulse, usually 40 mg/day for four consecutive days. Dexamethasone is a corticosteroid with an anti-inflammatory effect that is six times more potent than prednisone (40 mg dexamethasone is equivalent to 250 mg of prednisone) and has a longer biological half-life. This study (a systematic review and meta-analysis using several medical databases) evaluated the long-term efficacy and safety of high-dose corticosteroids as an initial treatment for children and adults with previously untreated ITP. Five trials compared high-dose dexamethasone with prednisone in adults. A total of 459 patients were assessed for long-term responses.

All the studies used the same dose of dexamethasone (40 mg/day for four days). Initial responses were assessed at 14 days, and long-term responses at 6 months. High-dose dexamethasone was associated with improved platelet count responses by 14 days in adults, fewer bleeding events, and less toxicity than prednisone over the course of treatment. In pooled data from the randomized trials researchers found no difference in durable platelet count response at six months in adults who were treated with high-dose dexamethasone or with the standard-dose prednisone. The high-dose dexamethasone responses occurred more rapidly and without any additional toxicities. Initial platelet count responses in the children with ITP were similar. Findings showed a 79% overall response rate with dexamethasone. Adverse events (such as GI distress or weight gain) were reported less frequently in patients who received high-dose dexamethasone. The researchers also concluded that high-dose dexamethasone might be preferred over prednisone for patients with severe ITP who require a rapid rise in platelet count, such as for bleeding.

Mithoowani S, Gregory-Miller K, Goy J, et al. “High-dose Dexamethasone Compared with Prednisone for Previously Untreated Primary Immune Thrombocytopenia: a Systematic Review and Meta-analysis.” The Lancet, Vol. 3, Oct. 2016, 489 -496.

Combining Immunosuppressants with a TPO May Be Good Strategy for Managing Multirefractory ITP

Blood logo

Previously, in chronic ITP patients refractory ITP was defined as lack of response to splenectomy and requirement for treatment to reduce risk of severe bleeding events. This multicenter study included 37 patients with multirefractory ITP (defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag). Patients with multirefractory ITP were more likely to have secondary ITP. The majority of them had ITP for 78 months (range of 6-450) before it was recognized. These ITP patients, on average, had experienced failure of 10 treatments (range 6 – 15).

By the end of the study, only 1 in 14 patients achieved response on immunosuppressant therapy (such as steroids) alone. However, 7 in 10 patients achieved response by an average of 15 months (range 6 – 32 months) when they received combined treatment with immunosuppressants and thrombopoietin–receptor agonists (TPO-RAs) (romiplostim or eltrombopag). During the course of the study 5 of the 37 patients died (3 with ITP, 2 with other causes), 15 patients had at least one bacterial infection, and 9 had at least one episode of thrombosis /clots. During the course of ITP, all the patients required several hospitalizations (average number of hospitalizations was 15). Researchers concluded that multirefractory ITP was associated with high morbidity and mortality. Their findings showed that combining an immunosuppressant treatment with a TPO-RA may be a good strategy for managing these patients with severe disease.

Mahevas M, Gerfraud-Valentin M, Moulis G, et al. “Characteristics, Outcome and Response to Therapy of Multirefractory Chronic Immune Thrombocytopenia.” Blood 2016, Sept. 22:128 (12): 1625-30. Doi: 10.1182/blood-2016-03-704734. Epub 2016 Jun 27.



FDA Warns Against Use of Popular Class of Fluoroquinolone Antibiotics

FDA logoThe U.S. Food and Drug Administration has issued an updated statement cautioning against the use of a common class of antibiotics, pointing to evidence that the drug doubles the risk for permanent nerve damage. The antibiotics class in question, Fluoroquinolones, have gained popularity as they combat infection from a wide range of bacteria and are as effective and fast acting as intravenous antibiotics. Sold as Ciprofloxacin (Cipro), Moxifloxacin (Avelox), and Levofloxacin (Levaquin), these drugs are commonly used to quickly and effectively treat patients with sinusitis, bronchitis, and uncomplicated urinary tract infections. However, their use has been accompanied by a range of serious side effects.

The FDA released their official statement on this class of antibiotics after receiving reports of a number of adverse events from fluoroquinolone use, such as muscle weakness, numbness, and pain. Many instances of fluoroquinolone use have also been correlated to peripheral neuropathy (nerve damage), retinal detachment, and kidney disease. A study by University of British Columbia researchers reported that examination of longitudinal medical records of one million American men with a history of peripheral neuropathy demonstrated a clear correlation between the disease and the prior use of fluoroquinolones. Researchers discovered that men who were given fluoroquinolones were twice as likely to be diagnosed with neuropathy compared with men who did not receive the antibiotic. An earlier study from the same researchers exhibited a link between retinal detachment and fluoroquinolone treatment.

U.S. Food and Drug Administration. “FDA Updates Warnings for Fluoroquinolone Antibiotics.” U.S. Food and Drug Administration. 7/26/2016.

Shore, Randy. “Popular Antibiotics Implicated in Nerve Damage, says study with B.C. links.” Vancouver Sun. 8/28/2014.



Improved Immune Function from Plant-based Diet that Aids Communication between Gut Microbiota and Genes

Illustration of DNA strandsWe often hear about the many health benefits of a plant-based diet, but did you know these benefits can alter your genes and enhance your immune system? A new study published in Molecular Cell examined the differences in gut bacteria between mice fed with mostly fresh fruits and vegetables, and those fed with simple sugars and fats. Researchers found that a plant-based diet fed to mice offered a more beneficial range of healthy nutrients to microbes that colonize their gut. These microbiota were more diverse than those of their “Western-diet” fed counterparts, and participated in increased interaction with the host’s genome.

The genome, which includes all of the DNA wound into genes within our bodies, remains relatively consistent throughout our lives. However, different environmental influences can “turn on” (upregulate) or “turn off” (downregulate) specific sections of our genes so that they are expressed, or activated. The microbiota of the mice in this study who were fed a plant-based diet were observed to produce nutrient-rich metabolites, which communicated with the genome, and in turn produced genetic changes in the gut, colon, and liver. These changes improved immune function and protected the body from infection. However, this microbiota metabolic communication was prevented in mice fed a diet rich in simple sugars and fats. Ultimately, these findings show clear evidence of a linkage between diet, gut microbiota, and overall host health, giving us all one more reason to eat our greens!

Paddock, Catharine, MD. “Gut Microbes Switch Host Genes On and Off Under Influence of Diet.” Medical News 11/25/2016.




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