'Should Women Stop ADHD Meds During Pregnancy?'

 Continuing dexamphetamine for attention deficit-hyperactivity disorder (ADHD) during pregnancy was not associated with a higher likelihood of adverse maternal and neonatal outcomes compared with stopping the medication during pregnancy. A population-based retrospective cohort study from Western Australia found, though, that women who had ceased taking the drug prior to becoming pregnant had the lowest odds of adverse outcomes.

Women who ceased use of the medication had greater odds of threatened abortion -- vaginal bleeding prior to 20 weeks' gestation -- compared with continuers (OR 2.28, 95% CI 1.00-5.15, P=0.049), reported researchers led by Danielle Russell, a PhD student at the University of Western Australia in Crawley, in Archives of Women's Mental Healthopens in a new tab or window.

However, unexposed women -- i.e., those who took dexamphetamine before pregnancy but not during -- had lower odds of multiple adverse outcomes versus those who continued taking the medication throughout their pregnancy:

• Preeclampsia (OR 0.58, 95% CI 0.35-0.97, P=0.037)
• Hypertension (OR 0.32, 95% CI 0.11-0.93, P=0.036)
• Postpartum hemorrhage (OR 0.57, 95% CI 0.41-0.80, P=0.001)
• Neonatal special care unit admittance (OR 0.16, 95% CI 0.12-0.20, P<0.001)
• Fetal distress (OR 0.73, 95% CI 0.54-0.99, P=0.042)

ADHD diagnoses are becoming more common among women, leading to more women of reproductive age taking ADHD medications. For that reason, Russell and co-authors sought to better understand the safety of dexamphetamine during pregnancy, she told MedPage Today.

"Those who had stopped taking the medication did have a greater risk of possibly losing their pregnancy, but we don't know if that's due to them stopping the medication and having a withdrawal, or if they were at risk of losing their pregnancy and therefore they stopped," Russell said.

Nancy Byatt, DO, MBA, a perinatal psychiatrist and executive director of the Lifeline for Families Center at UMass Chan Medical School in Worcester, Massachusetts, who was not involved in the study, said whenever a pregnant patient is being exposed to a medication, it's important to think about the risks from the medication, as well as the risk of untreated illness.

"ADHD itself also has risks," she noted.

Byatt recalled a patient who once told her, "'If I can't have access to the medication, I'm going to need to terminate my pregnancy, because I cannot take care of the four children I have at home.' That's a really good reason to stay on an ADHD medication."

There's also evidence that if ADHD isn't treated during pregnancy, risks of depression and anxiety may increase in the postpartum periodopens in a new tab or window, she added.

"So these are all the things [psychiatrists] are taking into account and this [study] gives us more information as we're weighing these risks and benefits," she said. But "we wouldn't make a sweeping recommendation based on really any one study; we take into account all the data, and what's most important is we take into account the ... person we're working with, with lived experiences of their own. There is never really a hard and fast rule."

For this study, the researchers used the Midwives Notification System (MNS), the Monitoring of Drugs of Dependence System (MODDS), the Hospital Morbidity Data Collection, and the WA Registry of Births, Deaths and Marriages.

Eligible study participants were identified by linking data from the MNS, which contains information for both mother and child, to the MODDS, which includes information on the dispensing of all Schedule 8 medications.

The researchers included 844 women who had been given dexamphetamine during pregnancy and gave birth from 2003 to 2018: 547 women continued dexamphetamine (mean age 29.2) and 297 ceased dexamphetamine before the end of the second trimester (mean age 28.6).

They also included 844 women in the unexposed group (mean age 27.2), who were dispensed dexamphetamine prior to pregnancy but not during pregnancy.

Women in the unexposed group were more likely to have been hospitalized with mental health conditions within the 5 years prior to conception compared with women who continued treatment (OR 1.58, 95% CI 1.18-2.12, P=0.002).

Those who ceased medication use were not significantly different from the group who continued in terms of smoking status, diagnosis of diabetes, number of previous pregnancies, mental health hospitalizations, and socioeconomic status, Russell and team noted.

A major limitation to the study was the researchers' inability to examine spontaneous abortions, as well as the study's small sample size and limited demographic variation, which could limit its generalizability.

Disclosures

This study was funded by the Department of Health Western Australia Merit Award and a National and Health Medical Research Council Fellowship.

The study authors reported no conflicts of interest.

Primary Source

Archives of Women's Mental Health

Source Reference: opens in a new tab or windowRussell DJ, et al "Investigating maternal and neonatal health outcomes associated with continuing or ceasing dexamphetamine treatment for women with attention-deficit hyperactivity disorder during pregnancy: a retrospective cohort study" Arch Wom Mental Health 2024; DOI: 10.1007/s00737-024-01450-4.

https://www.medpagetoday.com/obgyn/pregnancy/109110

Online Obesity Program Helped Primary Care Patients Lose Weight

 Pragmatic implementation of an automated online behavioral obesity treatment program that included 9 months of active maintenance helped people with overweight or obesity lose a clinically significant amount of weight by 12 and 24 months, a randomized trial showed.

In the intention-to-treat analysis, after a mean estimated weight loss of 3.6 kg (95% CI -4.3 to -2.9), or 7.9 lb, following a 3-month weight loss program among primary care patients, the amount of weight regained at 12 months in the two maintenance groups that involved additional patient engagement was significantly less compared with the control maintenance group (P=0.004):

• Monthly intervention group (nine monthly video lessons and 1 week of self-monitoring per month): 0.37 kg (95% CI -0.06 to 0.81)
• Refresher intervention group (an introductory session and two 4-week periods of lessons and self-monitoring at 7 and 10 months): 0.45 kg (95% CI 0.27-0.87)
• Control maintenance group (monthly online newsletters): 1.28 kg (95% CI 0.85-1.71)

This pattern persisted at 24 months, reported J. Graham Thomas, PhD, of the Weight Control and Diabetes Research Center in Providence, Rhode Island, and colleagues in JAMA Internal Medicineopens in a new tab or window.

"This study shows that a fully automated online obesity treatment program can produce beneficial results for many patients in real-world primary care settings," Thomas told MedPage Today. "We were encouraged to find that the online weight-loss program performed just as well in real-world primary care practices as it does in our previous highly controlled clinical trials."

These patients lost weight "at rates comparable" to those seen in studiesopens in a new tab or window in which the researchers were completely hands-on in every aspect of the program, he added.

Because the treatment program is online and fully automated, Thomas said it is quite practical for widespread implementation across primary care practices. "The data show that the primary care clinicians were able to implement the program independently, and patients were able to use it successfully."

Across all maintenance groups, age, sex, and race/ethnicity were not linked with the rate of weight regain, while greater self-monitoring and patient engagement with lessons were associated with significantly less weight regain. For example, patients who viewed at least four lessons had less weight regain at 12 months relative to those who were less engaged -- 0.46 kg versus 1.51 kg (1.01 lb vs 3.33 lb; P=0.004).

"Treatment outcomes were highly associated with program engagement," said Thomas. "Many patients did not engage with the program in a meaningful way and were less likely to lose weight. On the other hand, patients who engaged at a high level tended to achieve very good outcomes."

Because of this, he pointed out that "there is likely an important role for doctors in encouraging and supporting their use of a program like this to produce the best outcomes."

For this study, the researchers recruited patients from a Rhode Island primary care network with about 60 practices and 100 physicians. Eligible participants were ages 18 to 75 with overweight or obesity who were referred by their nurse care manager and enrolled from 2018 to 2020.

Thomas and team included 540 patients in the intention-to-treat analysis. Mean age was 52.8, 71.1% were women, 94.3% were white, and mean body mass index was 36.

The Rx Weight Loss program consisted of 12 weekly interactive 15-minute video lessons teaching evidence-based behavior-change strategies for weight loss like goal setting and problem solving. Patients submitted self-monitoring data including daily weight, minutes of moderate to vigorous physical activity, and energy intake, and received weekly automated tailored feedback.

Goals of the program were a weight loss of 0.5 to 1 kg (1.1-2.2 lb) per week, a calorie intake of 1,200 to 1,800 kcal per day tailored to their starting weight, and an activity goal that gradually increased to 150 minutes or more per week.

Weight was monitored from electronic medical records through 24 months.

In a per-protocol analysis of 253 participants who engaged with a maintenance intervention, mean weight loss at the end of the initial 3-month intervention was 6.19 kg (95% CI -7.25 to -5.13), or 13.6 lb. At 12 months, there was less weight regain in the monthly (0.61 kg [1.3 lb]) and refresher (0.96 kg [2.1 lb]) maintenance groups than in the control maintenance group (1.86 kg [4.1 lb]).

Disclosures

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases.

Thomas and co-authors reported relationships with the National Institutes of Health, Medifast, Lumme Health, the National Institute on Minority Health and Health Disparities, the Rhode Island Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, Brown University, and Noom.

Primary Source

JAMA Internal Medicine

Source Reference: opens in a new tab or windowThomas JG, et al "Pragmatic implementation of online obesity treatment and maintenance interventions in primary care" JAMA Intern Med 2024; DOI: 10.1001/jamainternmed.2023.8438.

https://www.medpagetoday.com/primarycare/obesity/109114

Sickle Cell Pain Hospitalizations Rose After CDC's Opioid Recs

 A downward trend in opioid prescribing practices for patients with sickle cell disease (SCD) followed the CDC's 2016 opioid guidelines for chronic pain, an analysis of claims data showed, but so did a steady increase in pain-related hospitalizations.

Compared with expected pre-guideline trends, the opioid dispensing rate, days of opioids supplied per prescription, and morphine-equivalent dosage all significantly declined from March 2016 to December 2019 among SCD patients (P<0.001 for all), reported researchers led by Hyeun Ah Kang, PhD, of the University of Texas at Austin.

Meanwhile, an upward trend in hospitalizations for vaso-occlusive crises (VOCs) accompanied those changes in prescribing, according to findings detailed in JAMA Internal Medicineopens in a new tab or window. In December 2019, about one in five SCD patients (19.6%) in the study had a VOC-related hospitalization, a full 7 percentage points higher compared with expected trends based on a scenario where the 2016 guidelines were never released (12.5%).

While the CDC's 2016 guidelineopens in a new tab or window was not intended to limit pain treatment for patients with SCD -- who often experience VOCs that may not be relieved by non-opioids -- the agency did not specifically exclude this group from its recommendations. The guidelines have been associated with decreased opioid use in the overall population and in patients with chronic pain.

"People with SCD are treated with excessive suspicion of faking pain and 'drug-seeking,' and are frequently undertreated for acute pain -- and there's good evidence that can increase the risk of hospitalization," said C. Patrick Carroll, MD, director of psychiatric services for the Johns Hopkins Sickle Cell Center for Adults in Baltimore, who was not involved in the study.

"That suspicion, along with lack of clinical expertise in an incredibly complex illness, render our patients vulnerable to swings in clinical culture around opioids, whether to undue optimism regarding chronic pain or excessive fear when treating acute pain," he told MedPage Today. "The guidelines were a pivot-point and catalyst for clinical culture change, and it's plausible they interacted with the factors I mentioned to produce unintended consequences -- and we have seen some evidence that acute care rates have increased."

The study findings are particularly important, said Kang and co-authors, because reducing hospitalizations and emergency department visits are considered major treatment goals both by SCD patients and their physicians.

Federal guideline and policymakers "should carefully consider the negative outcomes that their interventions may present in vulnerable populations, as well as clearly communicate the intention and scope of the interventions," they wrote.

The CDC, referring to "lessons learned" from the development of the 2016 guideline, issued an updated guideline in 2022opens in a new tab or window that specifically excludes SCD -- as well as cancer-related pain, palliative care, and end-of-life care -- from its opioid recommendations for chronic pain. The updated guideline recommends that in the case of SCD, clinicians should refer to the American Society of Hematology's 2020 guidelinesopens in a new tab or window on managing acute and chronic pain in SCD.

"While there are many aspects of the updated guidelines I applaud -- particularly a more careful approach to opioid failure and dose reductions in chronic pain -- what we owe people with SCD is a disease-specific evidence base for important clinical decision points, and developing multidisciplinary treatment centers that can guide implementation of good clinical care nationwide," Carroll said.

The study from Kang's group used health insurance claims data from the Merative MarketScan Commercial Database, ultimately including 14,979 patients with SCD (mean age 26 years) from January 2011 to December 2019. Individuals with SCD were included if they were 1 year of age or older, had no cancer diagnosis, and had pharmacy coverage for the month of measurement.

In January 2011, the opioid dispensing rate was 81.3 per 100 persons with SCD (81.3%). This rate declined during the pre-guideline period ending in February 2016 but accelerated after the March 2016 guideline. By December 2019, the dispensing rate for patients with SCD was 13 percentage points lower compared with a no-guideline scenario (57.6% vs 70.7%, respectively). Significant decreases were also seen in the number of days supplied and morphine milligram equivalents per prescription.

Monthly VOC-related hospitalization rates at the start of the study (23.1 per 100 patients) declined slightly up until the guidelines came out (0.10 per month), at which point the rate increased by 0.03 month until the end of the study.

In an exploratory subgroup analysis by age group, changes were seen to a greater degree among adult patients, but similar changes were seen in pediatric patients, notable since the guideline was intended to apply to patients 18 years and older with chronic pain.

Disclosures

The study was supported by the American Association of Colleges of Pharmacy New Investigator Award.

Kang had no disclosures. Several co-authors reported relationships with industry.

Carroll also had no disclosures.

Primary Source

JAMA Internal Medicine

Source Reference: opens in a new tab or windowKang HA, et al "Opioid prescribing and outcomes in patients with sickle cell disease post-2016 CDC guideline" JAMA Intern Med 2024; DOI: 10.1001/jamainternmed.2023.8538

https://www.medpagetoday.com/publichealthpolicy/opioids/109116

Novel Short-Duration TB Treatment Fizzles

 Most patients with tuberculosis (TB) who received a treatment regimen that included the repurposed leprosy drug clofazimine converted to negative sputum cultures after 12 weeks, but a substantial proportion went on to have unfavorable outcomes, according to an interim analysis of the phase IIc CloFast trial.

After 12 weeks of treatment with a clofazimine/rifapentine-containing regimen, 89% of participants with severe TB tested negative on a sputum culture, which was similar to the 90% of those receiving a standard-of-care regimen (adjusted HR 1.17, 90% CI 0.79-1.73), reported John Metcalfe, MD, PhD, MPH, of the University of California San Francisco, at the Conference on Retroviruses and Opportunistic Infectionsopens in a new tab or window.

However, at 65 weeks, 41% of patients on the clofazimine regimen developed unfavorable clinical or bacteriologic outcomes versus 29% in the standard-care group.

These findings led to the trial being terminated early, Metcalfe told attendees.

Metcalfe pointed out that 69% of participants had advanced, severe TB confirmed on chest x-ray, and 26% had a 3+ sputum acid-fast bacillus level. "This was not a low- or limited-risk population in any way," he said.

Conventional TB treatment consists of a multidrug regimen that must usually be taken for at least 6 months and has high rates of nonadherence and drug resistance. To address these issues, there has been interest in repurposing clofazimine, which showed promise of being rapidly and highly effective against TB in a mouse modelopens in a new tab or window, Metcalfe explained.

Metcalfe posited that the mouse model that the CloFast trial drew upon was likely not applicable to more severe TB pathology in human lungs and that the human-equivalent dose of clofazimine may also have been wrong.

During a Q&A session, Nicholas Paton, MD, of the National University of Singapore and investigator in the Truncate-TB trialopens in a new tab or window, noted that "we had a very similar high-dose clofazimine regimen for 2 months and had relatively low rates of unfavorable outcomes in the order of 11-13%. The differences are that we used twice the dose that you used and the study population obviously had milder disease. Before we totally dismiss clofazimine, it would be useful to try and put that data together."

Metcalfe said that another major drawback to the clofazimine regimen was the number of serious adverse events that emerged during the trial. Among participants receiving the clofazimine-based regimen, 45% developed grade 3 or higher adverse events through week 65 versus 16% in the standard-of-care arm. This difference was driven by a change in creatinine clearance, he said, and except for one other trial, that finding had not been previously described.

"We don't know whether this is an interference with the creatinine assay or if it reflects actual transient renal injury," he said. However, relatively few participants treated with clofazimine experienced distress from skin hyperpigmentation, a known side effect of the drug, or QT prolongation.

"Given that its toxicity and efficacy are questionable, this certainly tips the scales against clofazimine and opens the question of what should the future of clofazimine treatment for TB look like," Metcalfe added.

The CloFast trial enrolled a total of 104 patients from Malawi, South Africa, Zimbabwe, India, and Haiti. Of these participants, 58 were randomized to receive rifapentine/isoniazid/pyrazinamide/ethambutol/clofazimine for 12 weeks, and 31 were randomized to conventional treatment with rifampicin/isoniazid/pyrazinamide/ethambutol for 6 months. Fifteen patients were randomized to a third arm of the study, looking at pharmacokinetics to evaluate a clofazimine loading dose, but data from that arm were not included in the interim analysis.

Participants in the study were mostly male (78%), with a median age of 32, and 28% were living with HIV.

The primary outcomes of the study were time to a stable, negative TB liquid culture conversion through week 12 and the proportion of participants who experienced an adverse event of grade 3 or higher through week 65. The hazard ratio for the primary outcome was adjusted for HIV status and severe TB. The key secondary outcome was the proportion of participants with an unfavorable clinical or bacteriologic outcome by week 65.

Disclosures

The study was funded by the National Institute of Allergy and Infectious Diseases.

Metcalfe reported no relevant financial disclosures.

Paton has reported receiving grants or contracts from Janssen Pharmaceuticals.

Primary Source

Conference on Retroviruses and Opportunistic Infections

Source Reference: opens in a new tab or windowMetcalfe J "Provisional results from a 3-month clofazimine/rifapentine-containing regimen for drug-sensitive TB" CROI 2024; Abstract 164.

https://www.medpagetoday.com/meetingcoverage/croi/109117

Commonly Used Fingertip Pulse Oximeters Not Up to Snuff

 Commonly used types of fingertip pulse oximeters were not consistent in their performance, with more frequent issues when tested in participants with darker skin tones, and sometimes fell short of regulations and manufacturer claims, according to a study from the Open Oximetry Project.

Among 11 fingertip pulse oximeters used during hypoxemia in healthy participants, five devices had a root mean square error (ARMS) >3%, which falls outside the acceptable FDA performance range, reported Isabella Auchus, MD, of the University of California San Francisco, and co-authors.

In addition, nine devices had worse performance in participants in the darkest skin pigmentation category versus those in the lightest category, they noted in eBioMedicine.opens in a new tab or window

The reference device and eight other devices met International Organization for Standardization (ISO) criteria for ARMS of ≤4%, while 10 devices plus the reference device demonstrated higher ARMS in participants who were categorized at the lowest third of individual typology angle (ITA) values (having dark skin tones), compared with the highest third of ITA values (light skin tones) when measured at the area between the joint and the fingernail.

Seven devices and the reference device demonstrated a positive bias in participants who had darker pigmentation compared with those with lighter pigmentation. Most devices also demonstrated higher ARMS at lower arterial oxygen saturation (SaO2) levels, particularly among individuals with darker skin pigmentation.

"Our data support several steps that could be taken now to update regulatory guidance and improve performance standards," Auchus and team wrote. "The commonplace reliance on subjective, nonstandardized skin pigmentation assessment tools (e.g., pFP [perceived Fitzpatrick Scale]) is problematic and should be abandoned for several reasons, including the lack of standardized colors, inter-operator variability and bias, and the misappropriation of the initial purpose of the scales."

These findings come just over a month after an FDA advisory committee provided largely positive feedbackopens in a new tab or window to the agency's effort to improve the accuracy of pulse oximeters when used in darker-skinned patients. The FDA Medical Device Advisory Committee Anesthesiology and Respiratory Therapy Devices Panel did, however, raise some concerns, including the need for larger trials.

Studies dating back to the 1980s have uncovered the effects of dark skin pigmentation on currently used pulse oximeters. A study from last summer also showed that overestimations of Black patients' oxygen saturationopens in a new tab or window by pulse oximetry may have led to delays in COVID-19 treatment and an unrecognized need for therapy among Black patients.

The 11 pulse oximetry devices tested included the Nellcor, serving as the reference device, the Nonin Onyx Vantage 9590, Masimo Mightysat, Walgreens MD300CN350R, Zacurate CMS 500DL, Walgreens OxyWatch C20, Choice MMed MD300CN340, Zacurate 500C, Bodymed BDMOXMTRBLK, Roscoe POX-ROS, Contec CMS50M, and the Biolight M70. The devices range in cost from below $60 to approximately $199.

While there was a wide range in oxygen saturation (SpO2)-SaO2 error between devices, the Nonin Vantage 9590 and Masimo Mightysat were ultimately deemed to have the best performance, while the Biolight and Roscoe performed the most poorly.

Among the devices tested, the Contec, Biolight, Masimo, and Nonin had all previously received FDA 510(k) premarket notification clearance and had met ISO standard 80601-2-61.

Participants were monitored using the respective devices, with researchers observing inspired oxygen, nitrogen, and carbon dioxide partial pressures in real time. These values were also adjusted through a partial rebreathing circuit as a way to achieve stable target SaO2 plateaus between 70% and 100% and partial pressure of carbon dioxide (PaCO2) values of 35-45 mm Hg.

The devices were tested among 34 participants who provided 4,360 blood samples. Among these participants, 27% were Asian, 24% were Caucasian, 21% were Black, 15% were Hispanic, and 15% were multi-ethnic. The participant population was evenly split on sex, and median age was 26.5. All were non-obese, non-smokers who did not have lung disease or cardiovascular comorbidities.

Patient skin pigmentation was assessed subjectively via the pFP, which ranges from one to six, with one being the lightest skin pigmentation, and six being the darkest, and the ITA via spectrophotometry for more objective measurements at nine different anatomical sites.

Thirty-five percent of participants were determined to have level III skin pigmentation on the pFP, 29% had level IV, 15% had level V, 12% had level VI, 6% had level II, and 3% had level I.

Determining whether a participant was categorized as "darkly-pigmented" was dependent on if their pigment was assessed by subjective or objective measurements. The number of participants categorized as having dark skin pigment was reduced when using the objective cutoff of an ITA less than 30◦ compared with the subjective pFP classification.

"The FDA guidance and ISO standards at the time of this study do not adequately account for the potential impact of skin pigmentation on POX [pulse oximeter] performance," Auchus and colleagues wrote. "We recommend that the pFP scale and other nonstandardized, subjective skin color scales no longer be used for defining diversity of skin pigmentation in POX validation studies."

All pulse oximeter devices were assigned a minimum of two participants with a darker-pigmented skin tone that exceeded 15% of the study population, in accordance with FDA guidance.

Auchus and team noted that the decision to focus on relatively young, healthy participants in the study could limit the generalizability of the findings. Other potential limitations included the small sample size of oximeters, the low level of recruitment of patients with darker skin tones, and a lack of accounting for effects of perfusion on pulse oximeter performance, among others.

Disclosures

This study was conducted as part of the Open Oximetry Project funded by the Gordon and Betty Moore Foundation, Patrick J McGovern Foundation, and Robert Wood Johnson Foundation. The UCSF Hypoxia Research Laboratory receives funding from multiple industry sponsors to test the sponsors' devices for the purposes of product development and regulatory performance testing.

Auchus reported no disclosures. A co-author reported receiving consulting fees from the University of California San Francisco.

Primary Source

eBioMedicine

Source Reference: opens in a new tab or windowLeeb G, et al "The performance of 11 fingertip pulse oximeters during hypoxemia in healthy human participants with varied, quantified skin pigment" eBioMedicine 2024; DOI: 10.1016/j.ebiom.2024.105051.

https://www.medpagetoday.com/pulmonology/generalpulmonary/109103

'Breastfeeding While Taking MS Monoclonal Antibody Drugs Appears Safe'

 Exposure to multiple sclerosis (MS) monoclonal antibody treatment during breastfeeding appeared to have no negative effect on the early development or health of infants, registry data in Germany showed.

Over the first 3 years of follow-up, no links emerged between exposure to monoclonal antibody drugs and annual hospitalization (rate ratio [RR] 1.23, P=0.473), annual systemic antibiotic use (RR 1.55, P=0.093), developmental delay (OR 1.16, P=0.716), or weight at follow-up, reported Kerstin Hellwig, MD, of Ruhr University in Bochum, Germany, and co-authors in an abstract released in advance of the American Academy of Neurologyopens in a new tab or window annual meeting.

"Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life," Hellwig said in a statement.

"Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding. Yet MS can develop during the childbearing years of life," Hellwig noted.

"Since the risk of MS relapses increases after giving birth, some mothers may need or want to restart these therapies, so it is important to determine whether these medications -- through breast milk -- have a negative impact on a child's development," she added.

The study used data from the German Multiple Sclerosis and Pregnancy Registryopens in a new tab or window of women with MS and neuromyelitis optica spectrum disorders (NMOSD). The researchers assessed four drugs used during breastfeeding: natalizumab (Tysabri), ocrelizumab (Ocrevus), rituximab (Rituxan), and ofatumumab (Kesimpta).

Hellwig and colleagues studied 183 infants born to mothers taking monoclonal antibodies while breastfeeding; of these, 180 had mothers with MS and three had mothers with NMOSD. The researchers compared them with a control group of 183 infants whose mothers did not use monoclonal antibodies while breastfeeding, matched for exposure to MS medications shortly before or during pregnancy. There were no significant demographic differences between groups.

Monoclonal antibody exposure during breastfeeding started at a median of 19 days postpartum. The median duration of breastfeeding was 172 days.

Natalizumab was most commonly used (68.31%), followed by ocrelizumab (18.58%), rituximab (6.01%), and ofatumumab (5.46%). In two cases, treatment switched from natalizumab to ocrelizumab during breastfeeding; in one case, it switched from rituximab to ocrelizumab. Three children had previously been breastfed on glatiramer acetate (Copaxone or others) and two on interferons.

Only about one-third of the infants in the study were followed for the full 3 years, Hellwig said. Nonetheless, the research is valuable because it compares "outcomes in potentially exposed babies with those in a control group," observed Riley Bove, MD, MSc, of the University of California San Francisco, who wasn't involved in the study.

It's important to continue monitoring these children "to ensure that there are no longer-term risks of infection, growth difficulties, and potentially autoimmunity," Bove told MedPage Today.

Other studies that assess breastfeeding exposure to MS monoclonal antibodies are underway, she noted, including the open-label SOPRANINO trialopens in a new tab or window of B cell levels in infants of lactating women on ocrelizumab.

"The SOPRANINO study has finished enrollment and we expect a study readout within the next year," Bove said.

Disclosures

The German Multiple Sclerosis and Pregnancy Registry is partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH.

Hellwig reported relationships with Teva, Biogen, Novartis, Roche, Merck, Genzyme, Bayer, BMS, Janssen, and INC Research.

Bove reported relationships with Horizon, EMD Serono, TG Therapeutics, Janssen, Biogen, Roche, Genentech, Novartis, and Eli Lilly.

Primary Source

American Academy of Neurology

Source Reference: opens in a new tab or windowWitt L, et al "Child development after exposure to monoclonal antibodies during breastfeeding" AAN 2024.

https://www.medpagetoday.com/meetingcoverage/aan/109120

MedPAC Wrestles With How to Fix Deep Flaws in Medicare Advantage Quality Metrics

 The methods used to compare quality between one Medicare Advantage (MA) plan and another are so seriously flawed that the system needs an overhaul, members of the Medicare Payment Advisory Commission (MedPAC) suggested last week.

A commission review has determined the program "is costly and not a good basis for judging quality," MedPAC principal policy analyst Ledia Tabor, MPH, told the commission during a presentation Thursday. It does not promote the use of high-value care, nor provide beneficiaries with meaningful information about local plan quality, she said.

It's also important because currently, the quality program -- based on a five-star ratings system -- pays higher-rated MA plans bonuses of some $15 billion a year from the Medicare trust funds. However, nearly every plan gets a high score. According to the Centers for Medicare & Medicaid Services (CMS), the average score for 2024 plans is 4.04opens in a new tab or window stars, and only a few dozen MA plans received fewer than three stars. As of this year, 52% of beneficiaries are now enrolled in MA plans.

The commissioners' discussion about how to change the system came after Tabor explained a major part of the problem. Medicare uses more than 100 metrics in those star ratings for each plan under contract. But those measures are evaluated at the contract level -- nationally -- even when a contract covers as many as 2.6 million enrollees nationwide.

The commission has repeatedly, in 2010, 2018, and 2020opens in a new tab or window, recommended that plans be evaluated at local market-area levels since there is so much regional variation, with different providers and different plan networks.

What a beneficiary wants to know "is the MA score for my doctor. I don't really care about the aggregate plan number. I want to know my doctor, my hospital, how does MA perform in my community?" said commissioner Lynn Barr, MPH.

Commissioner Brian Miller, MD, MBA, noted that "we probably shouldn't have a 'Lake Wobegon effect' where the average MA plan is 4.5 stars in many counties." He added that there also should be a way to rate quality of care for fee-for-service (FFS) beneficiaries to compare them with MA plans. Miller said he is thinking of ways to rescue the rating system, although he quipped that it "still may need to go out back and meet its final demise."

The commissioners made their remarks after Tabor's presentationopens in a new tab or window of an alternative way of measuring MA quality of care: risk-adjusted rates of ambulatory care-sensitive (ACS) hospitalizations within each plan's market areas. These are hospitalizations for conditions that preventive strategies -- such as timely visits to a primary care provider or specialist, or certain screenings -- might have avoided.

The MedPAC analysis, based on 2021 MA encounter MedPAR (Medicare Provider Analysis and Review) data, showed wide variation in scores, with some market areas showing nearly twice the rate of avoidable ACS hospitalization rates as the better-performing market areas: 41.7 versus 22.4 admissions per 1,000 enrollees.

"The considerable variation in risk-adjusted ACS hospitalization rates across market areas suggests some relatively high performers that could be rewarded, as well as opportunities to improve the quality of care in some markets," Tabor said.

Some commissioners had suggestions for tweaking a metric on ACS hospitalizations.

Commissioner Lawrence Casalino, MD, PhD, suggested that including ED visits in the ACS hospitalizations metric might be useful in comparing MA plans regionally.

Commissioner Cheryl Damberg, PhD, MPH, wondered how these rates vary by the availability of primary care in the plan, or the amount of plan spending on primary care. "The plans could vary substantially," she said.

Commissioner Stacie Dusetzina, PhD, said that in her view, an important metric for comparing MA quality in the context of ACS hospitalizations is how easily enrollees are able to access specialty care, a marker for network adequacy.

Bringing quality metrics down to a local level is incredibly relevant because it's what patients want, said commissioner Greg Poulsen, MBA. "The same program is variable across geography. And it's based on the providers that they work with," he said. "The way they pay those providers can vary geographically."

One commissioner raised questions about some quality measures that, she said, possibly shouldn't be. "You may not agree with me," said commissioner Betty Rambur, PhD, RN, but the presentation under discussion "reminded me about how concerned I am about measurement-driven overscreening, screening-driven overtreatment, and the cascade of events that occur from that and which can cause people to become patients when they really shouldn't be."

She was referring to how improvements in treatment have diminished the mortality benefit from breast cancer screening, and how colonoscopy screening in much older people can cause dehydration or other harms.

MA vs Fee-for-Service 'Hornet's Nest'

The commissioners listened to a second analysis during the session: a review of literature comparing quality between MA plans and FFS, which has no star-rating system now.

But the task of that analysis was a tough one, said MedPAC senior analyst Katelyn Smalley, PhD, MSc. She said a review of literature in 2020 found some studies showed MA plans outperformed FFS on some metrics, while others reported better quality or patient experience in FFS than in MA, and still other studies found no difference at all.

So MedPAC staff looked for studies done since 2020. They found substantial variation in the populations studied, the metrics reviewed, the data sources used, and the beneficiary population subsets that were included. None of those studies could be extrapolated to a general population, Smalley said.

Even when studies used common metrics -- preventive care, readmissions, mortality, and surgical complications -- they differed on how they defined their outcomes. And all of the studies had methodological challenges that limited their reliability, she said.

Another problem Smalley noted is that MA plans tend to code more patient diagnoses than physicians treating FFS beneficiaries, so patients' health status in MA cannot be compared with that of patients in FFS.

She also said that "beneficiaries who choose to enroll in MA likely differ in meaningful ways from those who choose fee-for-service," which "does complicate comparisons between the programs when those differences are unobservable and are poorly understood."

"What a hornet's nest," said Barr.

"We're comparing apples and oranges.... I think it's incredibly important for this work for patients, taxpayers, and CMS to understand the quality of care they're getting with the choices they make. But I don't see a path forward in the current structure where we're actually going to get meaningful information. I honestly think we should abandon this work," Barr said. "I don't think you're ever going to get to an answer that says, 'This is fee-for-service versus MA,' because they are so different."

She noted that perhaps quality metrics in the Medicare Access and CHIP Reauthorization Act -- commonly known as MACRA -- could be synced with the same metrics in MA, "and instead start thinking about how we have one quality program for all of Medicare beneficiaries, and then we can start analyzing the differences."

Cheryl Clark has been a medical & science journalist for more than three decades.

https://www.medpagetoday.com/publichealthpolicy/medicare/109119