MS & RLS Leppien

injectable DMTs for MS: which safest, which safe during pregnancy, which premedicate and with what

glatiramer acetate, IFN-B

glatiramer is safest and preferred for pregnancy, though both can be used during pregnancy

premedicate interferons with diphenhydramine or NSAID/APAP to minimize cold/flu-like s/s

4 types of MS and which is most common

1. relapsing-remitting MS (RRMS) = most common, stable condition between flares

2. primary progressive MS (PPMS) = simple gradual upward trend

3. secondary progressive MS (SPMS) = starts like RRMS, becomes like PPMS over time

4. progressive relapsing MS = progressive worsening with flares and periods of slower progression during non-flares

what is used for acute MS relapse and for how long? metabolism?

IV methylprednisolone for 3-10 days

metabolized by 3A4

preferred DMTs for mild MS vs severe

mild: interferons, glatiramer, teriflunamide, fumarates

severe: monoclonal antibodies (natalizu, alemtuzu, ocrelizu, ofatumu)

what needs to be monitored throughout interferon therapy? (3 things)

1. CBC

2. LFTs

3. TSH

SP1 modulators: conditions to avoid, necessary monitoring (7), major adverse event. which can cause QT prolongation?

avoid: pregnancy (use barrier method during therapy if of childbearing potential), PML risk, heart failure, heart block, MI/stroke history

monitor: skin, eyes, CBC, LFTs, pulmonary function tests (PFTs), BP, EKG

• may also monitor for PML with MRI or antibody screening

major AE: progressive multifocal leukoencephalopathy (PML)

ALL can prolong QT

SP1 inhibitors, associated metabolism and inhibition, FDO (first dose observation) considerations

fingolimod (Gilenya): inhibit 3A4, FDO for 6 hours at start or if therapy interrupted ≥ 14d

ozanimod (Zeposia): inhibit MAO, inhibit 2C8, no FDO just monitor BP

ponesimod (Ponvory): inhibit 3A4, FDO fo 4 hours at start or interruption ≥ 4d

siponimod (Mayzent): inhibit 3A4, 2C9 substrate, FDO only required if cardiac history, titrate dose if interrupted ≥ 4d

fumarates for MS: monitoring required (3), administration considerations (1), pregnancy considerations

monitoring: CBC (including absolute lymphocyte count ALC), LFTs, JCV antibodies

admin: take with food, do not open/crush/sprinkle capsules

likely safe during pregnancy, better data for IFNs and GA

teriflunomide (Aubagio) DDI enzymes (2), clinical pearl, unique AE

DDI: 1A2 inducer, 2C8 inhibitor

TERATOGEN, use contraception and screen for pregnancy

unique AE: hair thinning

cladribine (Mavenclad) monitoring, BBW, screen for ()

monitor: CBC, ALC, LFT, pregnancy

BBW for malignancy and teratogenicity (contraception must be used)

screen for: VZV, HBV, HCV, HIV, TB

MS therapies with PML risk, no PML risk

risk: all mAbs, cladribine, fumarates, SP1 modulators

no risk: teriflunomide, IFNs, GA

among mAbs for mS: which have malignancy/breast cancer as AE, which need premedication for infusion rxn, which need micron filter, which REMS, which CI in HIV or active chronic infection, which CI in HBV

alemtuzumab = Lamtrada natalizumab = Tysabri ocrelizumab = ocrevus

ofatumumab

malignancy risk: alemtuzumab

breast cancer risk: ocrelizumab

pre-medicate: alemtuzumab, ocrelizumab

micron filter: ocrelizumab

REMS: alemtuzumab, natalizumab

HIV CI: alemtuzumab

HBV CI: ocrelizumab, ofatumumab

in whom can we consider D/Cing MS therapy?

patients 60 or older who have been stable on DMT for a prolonged period of time

condition/risk factor closely associated with RLS

iron deficiency, secondary to

1. CKD

2. pregnancy

3. anemia

when to give iron in RLS, preferred treatment

if ferritin < 75 OR

TSAT < 20%

ferrous sulfate 325 mg with 100mg vitamin C BID for 12 weeks, reassess iron levels