Autoimmune part 1 Flashcards
Treatment approach for Rheumatoid Arthritis (RA)
what medications are you using first in moderate to severe disease
what can be added on
RA Guidelines of Treatment
- treat early and reevaluate every 3 months to assess as needed
- treat to target: low disease activity or remission of disease state
RA Treatment
all pt. should start on a csDMARD: preferred agent = methotrexate considered the gold standard for treating RA
- methotrexate strongl advised over all others for moderate to severe disease activity
_______________________________________________________
in addition to methotrexate (while waiting for it to kick in)…
can add NSAID
- NSAID only for symptom relief; does not touch the RA course
- use scheduled, NOT PRN
can add glucocorticoid for no longer than 3 months
- for those with debilitaing disease and need to bridge waiting for DMARD to kick in
- low-dose long term can be used in difficult to control disease
- high doses only to suppress flared
- watch side effects
types of DMARD therapy
Medications: DMARDs
csDMARD: hydroxcloroquine, sulfasalazine, methotrexate, lefunomide
bDMARD: TNF-inhibtiors, IL-6, antiCD20
tsDMAR: JAK inhibitors
Treatment approach for Rheumatoid Arthritis (RA)
what medications are you using first in mild/low disease activity
1 = hydroxchloroquine
#2 = sulfasalaizine
#3 = methotrexate
Treatment approach for Rheumatoid Arthritis (RA)
when to switch from csDMARD to bDMARD
what is triple therapy for RA: including what medications
if pt. on two csDMARD (hydroxy. and methotrexate for example) and still needing symptom relief = add in a bDMARD/TsDMARD instead of adding a third csDMARD
Triple Therapy: hydroxychloroquine, sulfasalazine and methotrexate/or/leflunomide
- want to switch to a different class of med, instead of swapping within the class
- example: if on a bDMARD and its not working, swap to tsDMARD instead of swapping to another biologic
- switching to a DMARD is preferred instead of keeping thm on steroids
Treatment Approach for Ankylosing Spondylitits
for Active Disease
what if NSAIDs arent working then what do you add on
primary nonresponse v secondary nonresponse
Active Disease of AS
NSAIDS are strongly recommended first line
- give as a scheduled treatment, not PRN
- no one agent preferred over others
if NSAIDS alone arent working….
treatment with NSAIDS + TNF inhibitors
- certolizumab
- etanercept
- golimumab
- adalimumab
- inflixumab
if TNFi + NSAIDS arent working, or if CI to TNFi…
treatment with secukinumab or ixekizumab (IL-17)
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Primary nonresponse: pt. was on NSAID + TNFi and they havent reallt ever gotten good response: Swap to Il-17
Secondary nonresponse: pt. was on NSAID + TNFi and they initially had response, but no longer = can consider swapping to a different TNFinhibitor (if cant = JAK)
Treatment Approach for Ankylosing Spondylitis
for Stable Disease: how is deescaltion done
Stable AS
Treatment = de-escalated therapy
if on NSAID only: try de-escalting down to NSAID PRN instead of on schedule
if on NSAID + TNFi = d/c NSAID (try TNF only)
if on biologic only: continue it
Treatment Approach for SLE
what are the options
(which biologics, what is everyone on, what for joint pain,etc.)
typically, hydroxycholroquine + steroid
Options for SLE Treatment
Glucocorticoids : mainstay
- mainstay of treatment, given at low doses in shortest duration possible
Topical Glucocorticoids
- used for cutaneous lupus
NSAIDS
- used for intermittenet joint pain
Hydroxycholoriquine: mainstay
- all pt. with SLE will be on this
Biologics: specifically given for lupus nephritis
- belimumab
- rituximab : given for AA pt. with lupus nephritis or combo with cyclophosphamide
- these are the biologics specifically used for lupus
Immunosuppresives: for lupus nephritis
- cyclophosphamide
- mycophenolate mofetil
- azathioprine
- methotrexate
ensure there is adequate mental helath treatment for SLE pt = anxiety and depression
ensure propoer vit D supplementation: getting 400 IU/daily & check in 3 months
Drug Induced Lupus
what is it
what meds
Drug Induced Lupus
- onset with initaition of med, and when d/c mes it goes away
Medications
- hydralazine
- procanamide
- isoniazid
- methyldopa
- chlorpromazine
- TNFi
Scleroderma Treament Medications
(symptom relief)
for renal crisis
for early stiffness
for inflammatory arthritis
for skin invovlement
Glucocorticoids
- for symptom relief: stiffness and achy early stages
For Renal Crisis
- ACE-inhibotrs
- CCB
- ARB
- Alpha-blockers
For Inflammatory Arthritis
- methotrexate
- hydroxycholoraquine
- rituximab
- tocilizumb
For Skin Involvement
- methotrexate
- mycophenolate mofetil
- cyclophosphamide
Scleroderma Treatment options for
Interstitial Lung Disease
Pulmonary Artery HTN
Raynauds
Ulcers
For ILD
Induction Thearpy (1)
- mycophenolate mofetil
- cyclophosphamide
- rituximab
Maitnence
- mycophenolate mofetil
- azathioprine
- cyclophosphamide
For Pulmonary artery HTN
- PDE-5 inhibitors….
- sildenafil
- tadalafil
- vardenifil
- endothelrin receptors antagonists…
- ambrisentan
- bosentan
- macitentan
For Rayunads
- CCB
- ARB
- PDE-5
For Uclers
- CCB
- PDE-5
Cardiac
- low dose steroids, immunosuppresants, colchicine (for pericaridal)
- PPI for gut and metoproclpramide for promotility
Methotrexate
MOA
Dosing Considerations
Methotrexate: a csDMARD
MOA: inhibits cytokine production and purine biosynthesis via the folic acid pathway to inhibit cells
Dosing Considerations
- much more often given orally, but does have a SQ injection
- both are given weekly
- adminster with folic acid to help reduce SE
- if having issues, swap to SQ formulation before changing medication
Methotrexate
Labs : Baseline and Maitenence
Side Effects (which related tot he labs youre getting)
Methotrexate: csDMARD
Baseline Labs
- LFTs
- Hep B/C
- CBC with platlets
- SCr
- Pregnancy test
- CXR
Maitnence
- CBC with platelets
- LFTs
- SCr
Side Effects of Methotrexate
- hepatotoxic (hence the LFTs)
- bone marrow suppression & throbocytopenis (CBC and platelets)
- known teratogenic (pregnancy test)
- pneumonitis, fiberosis (CXR at start)
- GI upset: N/V/D = can be a big issue
to help decreasd these side effects: give folic acid!!!! (she says daily, dr. kelly says on non methotrexate days)
Conceling Points
- no alcohol
- proper contracention: teratogen
- take 1x weekly & take folic acid
- labs!!
- GI upset: folate should help
Leflunomide
use in therapy
MOA
Labs to Monitor: baseline and maintence
side effects
counceling
Leflunomide
- compareable efficacy to methotrexate for RA, but methotrexate still GS
MOA: inhibits pyramidine syntehsis resulting in anti-infllamtory effects
prodrug!!! with long half life
Labs
Baseline
- ALT
- CBC with platlelts
- pregnancy test
- TB test
Maitnence
- ALT
- CBC with platlets
Adverse Effects
- hepatotoxic (ALT)
- bone marrow suppresion and thrombocytopenia
- teratogenic
- HA (common)
- rash
- alopecia = reversible!!
- GI : N/V/D (but folic acid doesnt help)
Counceling
- alopecica: gorws back
- if want get pregnant: takes years to clear out
- stays in gallbladder/bile = need charocal and bile acide sequestrant to remove
Hydroxychloroquine
MOA
Monitoring unique (3)
other ADR
Hydroxycholoroquine : csDMARD
MOA: inhibits neutrophil and eosinophils ; decreasing inflammation and stops antigen-ab. reactions
Monitoring
EKG: at baseline then during treatment
- risk of QT-c Prolongation & cardiomyopathies
- can lead to HF and death
Eye Exam at baseline the yearly after 5 years on it
- retinal toxicity!!!
- can decreased night vision and peripheral vision
- this is IRREVERSIBLE
CBC: baseline & during treatment
- bone marrow suppression
SIde Effects - others
- hypoglycemia
- rash
- diarrhea
hydroxEEEE - E for EKG and Eyes
Sulfasalazine
MOA
Lab Monitoring baseline and maitnence
ADR
Sulfasalazine: csDMARD
prodrug
MOA: metabolized to active form to modulate inflammatory response
Labs
Baseline
- CBC with platlets
Maitnence
- CBC with platlets
ADR
- bone marrow suppresion & thrombocytopenia (CBC watches)
- HA
- rash
- hives and photosensitivity watch in sun
- GI: N/V/D
- urine and skin can turn a yellow/orange
- sulfa allaergy = do not use!!!!!!!
Councel
- sunscreen
- GI upset
- urine and skin = orange/yellow
- can be used in pregnancy
TNF inhibitors
uses
MOA
names
TNF inhibitors: bDMARDs
uses: for RA: used in combo with other csDMARDs, can be used as monotherapy in AS, etc.
MOA: they are monoclonal antibodies - therefore binding to the cytokine and preventing it from being able to bind to the receptor
Names (given as SQ or IV)
- inflixumab and golinumab MUST be given WITH methotrexate
- Inflixumab
- Golinumab
- Adalimumab
- Certolizumab
- Etanercept
I G ACE ( I Go ACE)
TNFi
BBW’s
reasons not use to them (pt. specifics)
TNF inhibitors
BBW
- increased risk of serious infections (even UTI, URi but serious life threatening ones too)
- increase risk fo malignancy
- increased risk of new onset or exacerbation of Heart Failure
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Reasons to Avoid Using TNFi
- active infection
- immunocompromised (HIV/AIDS: but weight risk/benefits)
- pt. with demyleinating disease (MS) : & those with 1st degree relative of MS
- those with Heart Failure : either directly cardiotoxic or excaerbate the underlying issue
inflixumab = contraindicated in moderate/severe HF : for these pt. can use a tsDMARD or csDMARD
Non TNF Biologic DMARDS
four: names
MOA for each class
non- TNF bDMARDS : given IV or SQ
rituximab: monoclonoal ab. agains CD20 on B-cells
- must be given with methotrexate
IL-6 inhibitors: work by blokcing the IL-6 receptors
toclizumab
sarilumab
co-stimulation inhibtor: inhibits T cells by binding to APCs (CD80 and 86)
Abatacept
IL-17 (used in AS active diseae)
- Ixekizumab
- secukinumab
Non TNFi bDMARDS
BBW
ADR
Abatacept (co-stimulator)
- serious infection risk
- serious risk of cancer
Rituximab: B cell Thearpy
- BBW: fatal infusion rxn
- BBW: severe mucocutaneous rxn
- BBW leukoencephalopathy
- BBW serious infections
Tocilizumab & Sarilumab
- BBW: serious infections
- increased cholesterols and lipids!! (monitor)
ALL
- bone marrow supression
- infusion site rxn
- antibody development
Non TNFi BDMARDs
Labs: Baseline and Maitnence
Tocilizumab and sarilumab specifics
Baseline
- hep B/C
- TB
- CBC with diff.
Maitnence
- watch for signs of hypersensitivity, infection and malignancy
- watch for loacal injection rxn, systemic infusion reaction for IV
Tocilizumab and sarilumab - specifically
baseline
- AST/ALT
- CBC with platlet s
- LIPIDS
Maitnence
- AST, ALT
- CBC with platlets
- LIPIDS
TsDMARD: JAK 2 Inhibitors
MOA
Plce in thearpy
names
JAK 2 Inhibitors :
Names
Tofacitinib
Baricitinib
Upadacitanib
Place in Thearpy: used for additional treatment if csDMARDS arent working, isntead of triple thearpy or using instead of bsDMARD if not working
MOA: intracellularly block transcription to stop ability to replicated
cannot be started if…
- ALC < 500
- ANC 1000
- Hg < 8
- check baseline labs
JAK 2 Inhibitors
ADR
BBW
ADR
- bone marrow suppresion
- GI perforation
- increased LFTs
- TB
- hyperlipidemai
- anemai
BBW
- serious infection
- increase mortality due to CVD
- malignancy
- Thromobosis (DVT and PE)
JAK 2 : Tofacitanib specifics
Labs baseline and maitnence
(this applies to all JAK 2 as well)
Baseline
- lymphocytes and neutrophils CBC with diff + platelets
- lipids
- LFTs
- PPd
- viral hepatitis
- pregnancy test
Maitnence
- lymphocytes
- neutrophils
- Hb
- LFTS
- lipids
Biologics used in SLE for Lupus Nephritis
Belimumab
Rituximab
Belimumab
MOA: apoptosis of B cells
- takes 16 weeks to work!
- used: in addition to standard therapy in active, autoantibody postive SLEP
- low response rate in blacks
Monitor
- psych, mood
- hypersensitivity reaction
- diarrhea/nauseas
- serious infections
RItuximab
- can be used in combo with cyclophosphamide
- can be used instead of belimumab in blacks with lupus nephritis
Immunosuppressant: Cyclophosphamide
MOA
uses
warnings
Monitoring
Cyclophosphamide
uses: for SLE lupuse nephritis
MOA:prevents DNA synthesis
prodrug!!!
WARNINGS
- hemorrhagicc cystitic and bladder cancer : because it accumulates in the bladder = stay hydrated
- infertility
Monitoring
- CBC with platlets
- SCr
- AST/ALT
Immunosuppressant: Mycophenlate mofetil (MM)
MOA
uses
MM
used: lupus nephritis
MOA: cystosatis effect of B and T cells
MOnitoring
- CBC with platlets
- SCr
- AST/ALT
- Chemistry
- CXR
ADR
- liver dysfunction
- bone marrow suppression
- pulmonary involvemenr
Immunosuppressants
Azathiprine
methotrexate (for lupus)
for lupus nephritis
Azathiprine
- less effective than cyclophosphimide
- but decreased need for steroids
methotrexate
- can be used here
- helps decreased need for steroids
Pregnancy and Lupus
High Risk
- pre-term labor, pre-eclampsie
- c-section
- maternal mortality
planning is important!!! lots of these agents are teratogenic
Cyclophosphamide: ovarian failure and infertility
goal = remission or controlled before trying
Immunizations and Lupus
Immunizations and immunosuppressant thearpy
inactive vaccines are ok
active vaccines: give 2-4 weeks before start the drug, or 3 montsh after stopping drug
