2) This program is supported by an educational grant from Sanofi and is intended for an audience of #healthcare providers. Accreditation statement and author disclosures at https://t.co/QO3HNwRSPJ.
FOLLOW US for expert-led education in #MS management!— MultipleSclerosis_CME (@ms_cme) January 3, 2023
4) In #MS, #BTKi may stop #B_cells from attacking #myelin. The idea of targeting BTK in #autoimmunity derives from the success of #CD20-directed antibodies such as #rituximab & #ocrelizumab as tx for #RA, #MS, and other disorders marked by #autoreactive B cells.
— MultipleSclerosis_CME (@ms_cme) January 3, 2023
6) Protein #kinases: enzymes that catalyze phosphorylation of proteins & thereby alter their substrate’s activity. Kinase signaling pathways represent the most common form of reversible post-translational modifications that control cellular function.
👉 🔓 https://t.co/be4MXJ5Lfw pic.twitter.com/XkhttGWZts— MultipleSclerosis_CME (@ms_cme) January 3, 2023
7b) #XLA is an inherited #immunodeficiency disease characterized by recurrent bacterial infections, due to a severe lack of #B_cell development in the bone marrow
XLA patients have very low numbers of circulating B cells and #hypogammaglobulinemia.— MultipleSclerosis_CME (@ms_cme) January 3, 2023
9) #BTK activation leads to:
👉Antigen presentation
👉Differentiation and #cytokine production
👉Antibody production pic.twitter.com/uygQjNUm24— MultipleSclerosis_CME (@ms_cme) January 3, 2023
11a) For #BTKi and #MS, there are therapeutic opportunities relative to #B_cell function and #autoantibody production
👉Autoantibody production may be preferentially reduced . . .— MultipleSclerosis_CME (@ms_cme) January 3, 2023
12) Not all #BTKi will have same effects. The #Tec protein family has multiple domains and effects vary by
👉domain target
👉selectivity
👉covalent v noncovalent interactions
👉reversibility
👉CNS penetration (thru #BBB)— MultipleSclerosis_CME (@ms_cme) January 3, 2023
14) Of the 267 patients who underwent randomization, 261 were included in the modified intention-to-treat #mITT analysis, after the exclusion of 6 patients owing to a lack of post-baseline #MRI assessments pic.twitter.com/zGJDYv6ETq
— MultipleSclerosis_CME (@ms_cme) January 3, 2023
15b) Baseline adjusted rate ratios for the total number of lesions over time vs were 1.45 in the #evobrutinib 25mg group (P=0.32), 0.30 in the 75mg QD group (P=0.005), and 0.44 in the evobrutinib 75mg BID group (P=0.06).
No significant differences on change in EDSS score. pic.twitter.com/UIxM31IdWs— MultipleSclerosis_CME (@ms_cme) January 3, 2023
15d) 213 (80%) of participants from double-blind phase 2 trial entered the open-label extension
👉164 (61%) completed ≥132 weeks of #OLE treatment
👉TEAEs were reported by 77.5%
👉No new safety concerns or increase in infections emerged— MultipleSclerosis_CME (@ms_cme) January 3, 2023
16) Now, the Ph 2 trial of #tolebrutinib:
🔓 https://t.co/nQDRzaICui pic.twitter.com/YpkMEmn2S6— MultipleSclerosis_CME (@ms_cme) January 3, 2023
17b) The primary efficacy EP was the number of new #gadolinium-enhancing lesions detected after 12wks of #tolebrutinib treatment (Cohort 1, wk 12; Cohort 2, wk 16), vs the scan 4 wks prior, compared to the lesions accumulated during 4 wks of placebo run-in period in Cohort 2 pic.twitter.com/a4QyzmRVBj
— MultipleSclerosis_CME (@ms_cme) January 3, 2023
17d) One #SAE (hospitalization due to MS relapse; 60 mg group) was reported. The most common non-serious adverse event was headache. No safety-related discontinuations occurred. pic.twitter.com/rKgXrmstdR
— MultipleSclerosis_CME (@ms_cme) January 3, 2023
18) So what have learned? #BTKi may be effective in #MS by ALL BUT which of the following mechanisms?
a. ⬇️ autoantibody production
b. ⬆️ macrophage activation
c. promote myelin repair
d. ⬇️innate immune system microenvironment promotion of neurodegeneration— MultipleSclerosis_CME (@ms_cme) January 3, 2023
20) Welcome back! We are talking about Bruton kinase inhibitors #BTKi & their therapeutic potential in the management of #MS, while u earn 🆓CE/#CME—#physicians #physicianassociate #nurses #nursepractitioner #pharmacists. FOLLOW US for expert-led MS education wholly on Twitter!
— MultipleSclerosis_CME (@ms_cme) January 4, 2023
22) Here’s what’s up with #fenebrutinib, a drug with no Ph 2 trials in #pwMS, but with extensive data in automimmune disease, particularly #RA and #SLE: pic.twitter.com/Q9USMWiAbk
— MultipleSclerosis_CME (@ms_cme) January 4, 2023
24) #Remibrutinib is being studied in the #REMODEL I and II trials in #RMS: pic.twitter.com/PBsSUgDkgE
— MultipleSclerosis_CME (@ms_cme) January 4, 2023
26) So a final knowledge ✔️: compared to 1st-gen #BTKi used to treat cancer, the 2nd-gen agents we have discussed are:
a. less brain-penetrant
b. more immunocompromising
c. less specific
d. more likely to⬇️pro-inflammatory cytokine release— MultipleSclerosis_CME (@ms_cme) January 4, 2023
28) Now go to https://t.co/bj3DdmpfVF and pick up your 🆓0.5hr CE/#CME certificate, courtesy of @academiccme. And don't leave until you FOLLOW US, so you don't miss our next expert-led #accredited program!
— MultipleSclerosis_CME (@ms_cme) January 4, 2023
