Demographics and baseline disease characteristics of Black and Hispanic patients with multiple sclerosis in the open-label, single-arm, multicenter, phase IV CHIMES trial

BACKGROUND: Black/African American patients with multiple sclerosis (BpwMS) and Hispanic/Latino patients with multiple sclerosis (HpwMS), who historically have been underrepresented in multiple sclerosis (MS) clinical trials, exhibit greater disease severity and more rapid disease progression than White patients with MS (WpwMS). The lack of diversity and inclusion in clinical trials, which may be due to barriers at the system, patient and study levels, impacts the ability to effectively assess risks, benefits and treatment responses in a generalized patient population. METHODS: CHIMES (Characterization of Ocrelizumab in Minorities With Multiple Sclerosis), an open-label, single-arm, multicenter, phase IV study of self-identified BpwMS and HpwMS aged 18-65 years with relapsing MS and an Expanded Disability Status Score (EDSS) of ≤5.5, was developed in collaboration with patients with MS, national advocacy groups and clinical researchers. Patients were enrolled at study centers across the US, including Puerto Rico, and 1 site in Kenya. RESULTS: A total of 182 patients enrolled in CHIMES: 113 (62.1%) were BpwMS, and 69 (37.9%) were HpwMS; the mean (SD) baseline EDSS score was 2.4 (1.4), and 62.6% of patients were treatment naive. Using the pooled non-BpwMS/HpwMS group in the OPERA ocrelizumab trials as a reference population, patients enrolled in CHIMES were younger, had a higher mean body mass and had a greater T2 lesion volume but similar T2 lesion number on MRI. CONCLUSION: BpwMS and HpwMS have been consistently underrepresented in clinical trials, limiting the understanding of disease biology and response to treatment in this population. Data from the CHIMES study revealed differences in demographics and some baseline disease characteristics and disease burden between BpwMS and HpwMS vs WpwMS. These differences could have an impact when assessing clinical outcomes in BpwMS and HpwMS. GOV IDENTIFIER: NCT04377555

Bryostatin Modulates Latent HIV-1 Infection via PKC and AMPK Signaling but Inhibits Acute Infection in a Receptor Independent Manner

HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC) -α and -δ, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC) involving stress induced AMP Kinase (AMPK) inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs

Expert Perspectives on COVID-19 Vaccination for People Living with Multiple Sclerosis

COVID-19 vaccines are safe for people living with MS on or off disease-modifying therapies and are important for the prevention of COVID-19. Antibody responses for individuals on certain DMTs may be diminished, however, T-cell responses may be preserved in those individuals. Data are lacking regarding optimal timing of vaccinations, and delaying disease-modifying therapies may increase the risk of disease activity and progression. In this perspective podcast, the authors recommend COVID-19 vaccination as soon as possible, regardless of timing considerations, in most cases. Graphical Plain Language Summar

Advancing Care and Outcomes for African American Patients With Multiple Sclerosis.

Multiple sclerosis (MS) has historically been underdiagnosed and undertreated among African Americans. Recent evidence suggests that African Americans with MS have a different clinical presentation, increased disease incidence and burden, and worsened long-term outcomes versus their White counterparts. Due to limited data available for African Americans in MS clinical trials, it is difficult to make informed, generalizable conclusions about the natural history, prognosis, and therapeutic response in this population. In this narrative review, we highlight the nature and magnitude of the health disparities experienced by African Americans with MS and underscore the pressing need to increase knowledge about and understanding of MS disease manifestations in this group. Additionally, we describe the mission and objectives of the recently established National African Americans with Multiple Sclerosis Registry (NAAMSR), which is intended to be a platform to advance the care of African Americans with MS and address health disparities they may experience

Real-World Safety and Effectiveness of Dimethyl Fumarate in Black or African American Patients with Multiple Sclerosis: 3-Year Results from ESTEEM.

INTRODUCTION: Black or African American (black/AA) patients with multiple sclerosis (MS) are reported to exhibit greater disease severity compared with non-black or non-AA patients. Whether differences exist in response to MS disease-modifying therapies remains uncertain, as MS clinical trials have included low numbers of non-white patients. We evaluated real-world safety and effectiveness of dimethyl fumarate (DMF) on MS disease activity in black/AA patients. METHODS: ESTEEM is an ongoing, 5-year, multinational, prospective study evaluating long-term safety and effectiveness of DMF in patients with MS. This interim analysis included patients newly prescribed DMF in routine practice at 394 sites globally. RESULTS: Overall, 4897 non-black/non-AA and 187 black/AA patients were analyzed; median (range) follow-up 18 (2-37) months. Unadjusted annualized relapse rates (ARRs) for 12 months before DMF initiation versus 36 months post DMF initiation, respectively, were: non-black/non-AA patients, 0.83 (95% CI 0.80-0.85) versus 0.10 (95% CI 0.09-0.10), 88% lower ARR (P \u3c 0.0001); black/AA patients, 0.68 (95% CI 0.58-0.80) versus 0.07 (95% CI 0.05-0.10), 90% lower ARR (P \u3c 0.0001). In total, 35 (19%) black/AA patients reported adverse events leading to treatment discontinuation; gastrointestinal disorders were most common (7%), consistent with non-black/non-AA patients (8%). Median lymphocyte counts decreased by 22% in the first year (vs 36% in non-black/non-AA patients), then remained stable and above lower limit of normal in most patients. CONCLUSIONS: Relapse rates remained low in black/AA patients, consistent with non-black/non-AA patients. The safety profile of DMF in black/AA patients was consistent with that in the non-black/non-AA ESTEEM population, although lymphocyte decrease was less pronounced in black/AA patients