Public Release: 

In phase 3 trial, rituximab not associated with clinical improvement in patients with ME/CFS

American College of Physicians

1. In phase 3 trial, rituximab not associated with clinical improvement in patients with ME/CFS

Abstract: http://annals.org/aim/article/doi/10.7326/M18-1451
Editorial: http://annals.org/aim/article/doi/10.7326/M19-0643
URLs go live when the embargo lifts

In a phase 3 randomized, double-blind, placebo-controlled trial, B-cell depletion using several infusions of rituximab over 12 months was not associated with clinical improvement in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The findings are published in Annals of Internal Medicine.

It is not known what causes ME/CFS, but the disease is associated with substantial morbidity. Patients report malaise, fatigue, sleep disturbances, cognitive symptoms, sensory hypersensitivity (including pain), and other symptoms related to autonomic or immune function. The disease is associated with greatly reduced quality of life and high socioeconomic costs and no treatments have proven effective. However, previous phase 2 trials indicated benefit from B-lymphocyte depletion.

Researchers from Haukeland University Hospital, Norway randomly assigned 151 adults with ME/CFS to receive either placebo (n = 74) or rituximab during the study period. Participants had the treatment or sham infusion 2 weeks apart, followed by 4 maintenance infusions at 3, 6, 9, and 12 months. Over 2 years of follow up, the researchers looked for improved fatigue scores and self-reported function. In contrast to preliminary observations in phase 1 and 2 trials, the authors did not find any statistically significant differences between groups in any measure. According to the authors, these study results weaken the case for an important role of rituximab in treating ME/CFS.

The author of an accompanying editorial from Johns Hopkins University School of Medicine praises the sound methodology and sophistication of the trial and notes that a substantial challenge in ME/CFS research is the heterogeneity of the illness. For this reason, future research should be stratified by disease duration and may need to exclude or accommodate for specific subgroups, such as those who are unlikely to respond to treatment and those with a current flare during the trial period.

Media contact: For an embargoed PDF, please contact Lauren Evans at laevans@acponline.org. To interview the senior clinical author, Øystein Fluge, MD, PhD, please contact Erik Vigander at erik.vigander@helse-bergen.no or +47 901 33 771. The author of the editorial, Peter C. Rowe, MD, can be reached through Vanessa McMains, PhD at vmcmain1@jhmi.edu.

2. Dolutegravir should be considered in women of child-bearing age with HIV

Abstract: http://annals.org/aim/article/doi/10.7326/M18-3358
Editorial: http://annals.org/aim/article/doi/10.7326/M19-0641
URLs go live when the embargo lifts

Despite the potential risks for neural tube defects, dolutegravir may lead to fewer deaths among women, as well as fewer overall HIV transmissions compared with efavirenz, and therefore, should be considered for treating HIV in women of child-bearing potential in resource-limited settings. Findings from a modeling study are published in Annals of Internal Medicine.

Dolutegravir-based antiretroviral therapy (ART) offers superior efficacy and tolerability compared with the current standard of care, efavirenz-based ART, but dolutegravir has recently been associated with neural tube defects in newborns if used by women at conception. Neural tube defects result in nearly 100 percent mortality in resource-limited settings. From a public health perspective, the risk for such defects potentially attributable to dolutegravir needs to be weighed against the potential benefits.

Researchers from Massachusetts General Hospital used a computer model to examine ART policies for 3.1 million women of child-bearing potential in South Africa. They focused on outcomes of maternal and child deaths, sexual and perinatal transmission, and neural tube defects. The model evaluated three approaches to treatment: efavirenz for all; dolutegravir for all; and the WHO-recommended approach of using efavirenz without and dolutegravir with contraception. They found that dolutegravir for all outperformed other scenarios, resulting in the smallest number of deaths among women and the fewest HIV transmission events, with the tradeoff of modestly more pediatric deaths. Dolutegravir for all also increased pediatric HIV-free survival compared with efavirenz for all. The authors suggest that since using dolutegravir would avert more than threefold more deaths among women with HIV than pediatric deaths added in South Africa, the blanket policy of favoring efavirenz over dolutegravir for women of child-bearing potential should be reconsidered.

According to the authors of an accompanying editorial from the David Geffen School of Medicine at the University of California, Los Angeles, this study highlights the complexity of decision making regarding treatment of pregnant women. This model may help guide policy-makers in critically balancing benefits and risks as they make decisions regarding national ART policy.

Media contact: For an embargoed PDF, please contact Lauren Evans at laevans@acponline.org. To interview the lead author, Caitlin M. Dugdale, MD, please contact Noah Brown at nbrown9@partners.org or 617-643-3907. To reach the author of the editorial, please contact Phil Hampton at phampton@mednet.ucla.edu.

###

Also New in this issue:

Deliberate Indifference: Inadequate Health Care in U.S. Prisons
Ashley Hurst, JD, MDiv, MA; Brenda Castan? eda, JD; and Erika Ramsdale, MD
Ideas and Opinions

Abstract: http://annals.org/aim/article/doi/10.7326/M17-3154

What Type of Price Transparency Do We Need in Health Care?
Austin Frakt, PhD, and Ateev Mehrotra, MD, MPH
Ideas and Opinions

Abstract: http://annals.org/aim/article/doi/10.7326/M19-0534

Medicare for All and Its Rivals: New Offshoots of Old Health Policy Roots
Steffie Woolhandler, MD, MPH; David U. Himmelstein, MD
Ideas and Opinions

Abstract: http://annals.org/aim/article/doi/10.7326/M19-0780

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.