Side Effects and COVID-19 Vaccine Hesitancy
Vaccine hesitancy is increasingly a roadblock toward achieving herd immunity in many nations, including the United States. Reports of adverse effects, both common, such as fever and body aches, and rare but life-threatening, such as cerebral blood clots, have given fuel to these concerns. It’s tempting to refrain from discussing vaccine side effects with the public, but rebuilding trust in our health care institutions is important, and maintaining transparency around the costs and benefits of COVID-19 vaccinations can increase such trust.
The reports of what is now termed vaccine-induced thrombotic thrombocytopenia (VITT) after vaccination with the viral vector vaccines produced by Astra Zeneca and Johnson & Johnson/Janssen, are contributing to this vaccine hesitancy. The FDA and the Centers for Disease Control, after six cases of cerebral venous sinus thrombosis combined with thrombocytopenia were reported in vaccinated people, ordered a pause in distribution of the J&J/Janssen vaccine in the United States. Ultimately, about 15 cases of VITT were identified, all occurring in women ages 18 to 48 within a median of 9 days after vaccination. Although the incidence is very low, its life-threatening nature made it imperative that clinicians learn how to recognize and treat it. These blood clots are thought to be related to the autoantibody platelet factor 4, which is responsible for heparin-induced thrombotic thrombocytopenia, and therefore cannot be treated by heparin or related anticoagulants. With this in mind, providers are encouraged to ask patients presenting with low platelet counts or with evidence of blood clots about recent vaccinations so they can manage the syndrome with IV immunoglobulins and other supportive care. Women, especially pregnant and postpartum women, should be encouraged to receive the mRNA vaccines.
Other, non-life-threatening adverse events are also contributing to vaccine hesitancy. A recent article in the New York Times reported that up to 8% of vaccinated individuals are passing up the second dose because of reports of more severe reactions to the second dose. The challenge here is in educating the public that those reactions are actually a function of the vaccine working. It reflects the amnestic, or memory, response, as the body’s immune system remembers exposure to the spike protein of the SARS-CoV2 virus.
Combatting vaccine hesitancy will require transparency by public health authorities to enable recognition and treatment of rare but life-threatening adverse reactions and clear communication of the risks and benefits of the vaccine versus infection with the actual virus. Although the common adverse effects—fever, headache, body aches—can be troublesome, they are brief, most occurring within the first few days after vaccination. But the viral infection carries a mortality rate of about 2%, and long-haul symptoms are estimated to occur in between 10% and 40% of infected individuals.
(Lahey, T. (2021, April 13). Op-ed: J&J vax pause is actually good for COVID long game. MedPage Today. https://www.medpagetoday.com/infectiousdisease/covid19vaccine/92069; Walker, M. (2021, April 13). J&J COVID vaccine pause not an overreaction, officials say. Med Page Today. https://www.medpagetoday.com/infectiousdisease/covid19vaccine/92068; Marshall, S. & Salahi, L. (2021, May 5). Are side effects why many pass on COVID shots? [Audio podcast]. MedPage Today. https://www.medpagetoday.com/podcasts/trackthevax/92422)
Released: May 2021
© 2021 Wolters Kluwer
COVID-19 Vaccines for Adults with Parkinson Disease
Those with advanced Parkinson disease are at high risk of serious, life-threatening SARS-CoV2 disease, so the arrival of COVID-19 vaccines has created hope for them. Although the risk of infection with the virus is not higher for patients with Parkinson disease, the risk of experiencing severe respiratory disease and long-term sequelae does appear to be elevated among those who do become infected, especially among those with more advanced Parkinson disease. Motor and nonmotor symptoms of Parkinson disease can worsen as a result of COVID-19, and the risk of death from COVID-19 also appears to be higher than in the general population.
Concerns, however, have been expressed by patients, their families, and clinicians about the safety and efficacy of the vaccine in those with Parkinson disease. In particular, concerns have been raised about the effects of the COVID vaccine on the disease process and on dopaminergic medications.
An article in the Journal of Parkinson Disease sought to lay out recommendations from the International Parkinson and Movement Disorder Society (IPDMS). The IPDMS made the following points:
- The vaccines currently available under the Emergency Use Authorization, both mRNA and viral vector vaccines, produce immunization through mechanisms not known to interact with the neurodegenerative process in Parkinson disease.
- Reported data on those vaccines shows no difference in the types or incidence of side effects in persons with Parkinson disease compared to the general population.
- COVID-19 vaccines are not known to interfere with current Parkinson disease therapies.
The authors of the article recommend that patients with Parkinson disease receive the vaccine, unless they have specific contraindications, among them being frail and elderly or terminally ill patients living in long-term care facilities. They also encourage patients with Parkinson disease to discuss the vaccination with their physicians and encourage clinicians to stay up-to-date with published reports on the vaccine rollout. (Bloem, B. R., et al. (2021). COVID-19 vaccination for persons with Parkinson’s disease: Light at the end of the tunnel? J Parkinson Dis; 11(1): 3-8. https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd212573)
Released: May 2021
© 2021 Wolters Kluwer
Choosing the Best Epilepsy Drugs for Newly Diagnosed Patients
The Phase IV open-label Standard New Epileptic Drug (SANAD II) studies compared newer therapies such as levetiracetam and zonisamide to older antiseizure medications such as valproate to determine the noninferiority of the new drugs to standard therapy. Published in The Lancet, SANAD II consisted of two pragmatic, open-label, randomized trials: one that compared the long-term clinical effectiveness of valproate and levetiracetam as treatment of generalized seizures (the second compared lamotrigine, levetiracetam, and zonisamide to determine if the newer drugs are appropriate first-line therapies for focal epilepsy).
The generalized epilepsy study recruited patients from 69 adult and pediatric neurology services in the UK. The median age was 13.9 years, and 65% of those enrolled were male; 397 patients had generalized epilepsy and 123 unclassified epilepsy. The studies were designed as noninferiority trials and, in new patients with generalized epilepsy, levetiracetam didn’t meet the noninferiority criteria compared with valproate in time to 12-month remissions from seizures on intent-to-treat analysis, with a hazard ratio (HR) of 1.19; on per protocol analysis, valproate was found to be clearly superior (HR, 1.68). Valproate was also superior to levetiracetam for time to treatment failure (HR, 0.65) and time to first subsequent seizures (HR, 0.82). At 2 years, there was a 15% difference in the treatment failure rate for levetiracetam compared with valproate. Valproate was also superior in cost-effectiveness, based on differences in costs and quality-adjusted life-years.
These findings have an important clinical consequence. Valproate has long been a first-line treatment for newly diagnosed generalized epilepsy, but the FDA has warned against its use in women of childbearing age due to the known risk of birth defects. Levetiracetam has increasingly been prescribed for these women, so these findings present a dilemma for them. Each woman and her clinicians need to weigh the reality of the teratogenic effects of valproate against the lower effectiveness of levetiracetam. (George, J. (2021, April 12). Epilepsy drugs for newly diagnosed patients: What's best? MedPage Today. https://www.medpagetoday.com/neurology/seizures/92051; Cross, J. H. & Tomson, T. (2021). Newer versus older antiseizure medications: further forward? The Lancet. 397(10282): 1327-1329. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00435-9/fulltext; Marson, A., et al. (2021). The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: An open-label, non-inferiority, multicentre, phase 4, randomised controlled trial. The Lancet; 397(10282): 1375-1386. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00246-4/fulltext; Marson, A., et al. (2021). The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial. The Lancet; 397(10282): 1363-1374. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00247-6/fulltext)
Released: May 2021
© 2021 Wolters Kluwer
Addition of Nivolumab to Chemotherapy Improves Response in Operable Lung Cancer
Adding the anti-PS-1 monoclonal antibody nivolumab to standard platinum-based chemotherapy before surgery increased the pathological complete response (pCR) rate in patients with operable lung cancer. These results of the Checkmate-816 trial were reported at the American Association for Cancer Research (AACR) annual meeting, held virtually from Philadelphia.
The multicenter, Phase III trial enrolled 358 patients with newly diagnosed, stages Ib to IIIa non–small-cell lung cancer (NSCLC) and no known EGFR or ALK alterations. The study evaluated two combination strategies: fixed-dose nivolumab and platinum-based chemotherapy and weight-adjusted nivolumab and ipilimumab, and compared them to chemotherapy alone. However, the presentation at the AACR meeting discussed only the data for the nivolumab-chemotherapy arm. Patients underwent surgery within 6 weeks, after restaging based on radiologic findings; after surgery, patients could receive chemotherapy with or without radiotherapy.
The primary endpoint, pCR, was defined as no residual viable tumor when the resected lung specimen and the sampled lymph nodes were examined after surgery. Adding nivolumab to chemotherapy produced an improvement in pCR, to 24% of patients, compared with 2.2% in the chemotherapy arm alone. Combination therapy also improved the major pathologic response rate, which is defined as 10% or less residual viable tumor cells in the lung and lymph nodes, to 36.9%, compared with 8.9% in the chemotherapy alone arm. Presurgical objective response rate was 54% with nivolumab combination vs. 37% with chemotherapy alone. The addition of nivolumab maintained a tolerable safety profile, and the rates of adverse events leading to surgery delay or cancellation were low: 83% of those in the nivolumab combination arm underwent surgery, as did 75% of those treated with chemotherapy alone. Surgery was delayed in 21% of nivolumab patients and 18% of chemotherapy patients.
These findings, along with data from several retrospective studies that show a clear trend toward improved survival in those patients who achieve pCR, are encouraging. The study is ongoing, so results for event-free survival are still to come.
(Bankhead, C. (2021, April 11). A win for nivolumab as preoperative therapy for lung cancer. MedPage Today. https://www.medpagetoday.com/meetingcoverage/aacr/92038; AACR. News Release. (2021, April 10). Neoadjuvant nivolumab plus chemotherapy increased pathological complete response rate in CheckMate-816 lung cancer trial. https://www.aacr.org/about-the-aacr/newsroom/news-releases/neoadjuvant-nivolumab-plus-chemotherapy-increased-pathological-complete-response-rate-in-checkmate-816-lung-cancer-trial/)
Released: May 2021
© 2021 Wolters Kluwer