FDA Approves First Treatment for Lambert-Eaton Myasthenic Syndrome, A Rare Autoimmune Disorder

FDA News Release. November 28, 2018. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm627093.htm (accessed 12/4/18).

The US Food and Drug Administration (FDA) has approved amifampridine (Firdapse) tablets as the first ever treatment of the rare autoimmune disorder Lambert-Eaton myasthenic syndrome (LEMS) in adults (1).

In LEMS, the immune system attacks the neuromuscular junction and disrupts the ability of nerve cells to send signals to muscle cells. LEMS may be associated with other autoimmune diseases, but more commonly occurs in patients with cancer such as small cell lung cancer, where its onset precedes or coincides with the diagnosis of cancer. The prevalence of LEMS is estimated to be three per million individuals worldwide.

The efficacy of amifampridine was studied in a pair of clinical trials involved 64 adult patients administered either amifampridine or placebo. Using the 13-item, physician-rated categorial Quantitative Myasthenia Gravis scale to assess for muscle weakness, as well as the seven-point, patient-rated Subject Global Impression, investigators assessed the therapy’s benefit for LEMS’ most prevalent symptoms. For both measures, patients treated with amifampridine reported greater benefits than those administered placebo.

In a statement included with the announced approval, Billy Dunn, MD, director of the Division of Neurology Products in the FDA’S Center for Drug Evaluation and Research, noted the burdens faced by the 3 million-patient population. “There has been a long-standing need for a treatment for this rare disorder,” Dunn said. “Patients with LEMS have significant weakness and fatigue that can often cause great difficulties with daily activities.”

The most common side effects experienced by patients in the clinical trials were burning or prickling sensation (paresthesia), upper respiratory tract infection, abdominal pain, nausea, diarrhea, headache, elevated liver enzymes, back pain, hypertension and muscle spasms. Seizures have been observed in patients without a history of seizures. Because it affects voltage-gated ion channels, it is contraindicated in people with long QT syndrome and in people taking a drug that might prolong QT like sultopride, disopyramide, cisapride, domperidone, rifampicin or ketoconazole. It is also contraindicated in people with epilepsy or badly controlled asthma.

Does Point-of-Care Ultrasonography Improve Clinical Outcomes in Emergency Department Patients with Undifferentiated Hypotension?

Atkinson PR, Milne J, Diegelmann L, et al. Ann Emerg Med. 2018 Oct;72(4):478-89. [CrossRef] [PubMed]

Point-of-care ultrasonography protocols are commonly used in the initial management of patients with undifferentiated hypotension in the emergency department (ED) or the intensive care unit (ICU). However, there is little published evidence for any mortality benefit. The authors compared a point-of-care ultrasonography protocol versus standard care without point-of-care ultrasonography for survival and clinical outcomes. Follow-up was completed for 270 of 273 patients. The most common diagnosis in more than half the patients was occult sepsis. No important differences between the two groups for 30-day survival. There were no important differences in rates of computed tomography (CT) scanning, inotrope or intravenous fluid use, and ICU or total length of stay. The authors conclude that addition of a point-of-care ultrasonography protocol to standard care may not translate into benefits in survival, length of stay, rates of CT scanning, inotrope use, or fluid administration.

E-cigarette Use and Subsequent Smoking Frequency Among Adolescents

Barrington-Trimis JL, Kong G, Leventhal AM, et al. Pediatrics. November 05, 2018. [Epub ahead of print] [CrossRef] [PubMed]

Electronic cigarette (e-cigarette) use is associated with cigarette initiation among adolescents. However, it is unclear whether e-cigarette use is associated with more frequent cigarette use after initiation. The authors pooled data from 3 prospective cohort studies in California and Connecticut (baseline: 2013–2014; follow-up: 2014–2016; N = 6258). Among baseline never smokers, e-cigarette users had greater odds of subsequent experimental (odds ratio [OR] = 4.58; 95% confidence interval [CI]: 3.56–5.88), infrequent (OR = 4.27; 95% CI: 2.75–6.62) or frequent (OR = 3.51; 95% CI: 1.97–6.24) cigarette use. Baseline past-30-day exclusive cigarette use was associated with higher odds at follow-up of exclusive cigarette or dual product use than of exclusive e-cigarette use. The authors conclude that tobacco control policy to reduce adolescent use of both e-cigarettes and cigarettes is needed to prevent progression to more frequent tobacco use patterns.

Changes in Prevalence of Health Care-Associated Infections in U.S. Hospitals

Magill SS, O'Leary E, Janelle SJ, et al. N Engl J Med. 2018 Nov 1;379(18):1732-1744. [CrossRef] [PubMed]

Health care-associated infections (HCAI) have been associated with poorer outcomes including increased mortality. Programs have been initiated by Centers for Medicare and Medicaid Services (CMS) to reduce reimbursement to hospitals based on their HCAI rate. The authors conducted a point-prevalence self-reported survey of selected US hospitals and compared it to 2011 data. The results showed that 3.2% of hospitalized patients had HACI in 2015 which was significantly lower than the 4.0% reported in 2011. However, mortality did not differ. The results suggest that the hospital-reported HACI has declined but was not associated with the dramatic reduction in mortality claimed by CMS.

Benefits and Harms of Antihypertensive Treatment in Low-Risk Patients with Mild Hypertension

Sheppard JP, Stevens S, Stevens R, Martin U, Mant J, Hobbs FDR, McManus RJ. JAMA Intern Med. October 29, 2018. [CrossRef]

Evidence to support initiation of pharmacologic treatment in low-risk patients with mild hypertension is inconclusive, with previous trials underpowered to demonstrate benefit. Clinical guidelines across the world are contradictory. In this longitudinal cohort study, data were extracted from the Clinical Practice Research Datalink, from January 1, 1998, through September 30, 2015, for patients aged 18 to 74 years who had mild hypertension (untreated blood pressure of 140/90-159/99 mm Hg) and no previous treatment. A total of 19,143 treated patients were matched to 19,143 similar untreated patients. During a median follow-up period of 5.8 years, no evidence of an association was found between antihypertensive treatment and mortality. Treatment was associated with an increased risk of adverse events, including hypotension, syncope, electrolyte abnormalities, and acute kidney injury. The authors found no evidence to support guideline recommendations that encourage initiation of treatment in patients with low-risk mild hypertension but an increased risk of adverse events.