Lecture 9 - Rheumatoid Arthritis Flashcards
Meds most effective for acute pain relief in RA?
NSAIDs
Ibuprofen, also prednisone
Which meds have most risk of re-activating Hep B?
Rituximab, -mabs are immunosuppressive
Which med required periodic eye exams for RA?
Hydroxychloroquine
Med with highest risk for infections?
Etanercept
Which RA med is safe for pregnancy?
sulfasalazine
Meds most appropriate for someone with kerato-conjunvitis related to RA?
Restasis
RA risks
Associated with HLA DR4 MHC II Antigen
women 3-4X > men
Smokers are 4x > non-smokers
Caucasians higher risk than AA, native Americans 5-6X > Caucasians
Some Interleukin and Cytokine factors for RA?
IL-1, TNF-a, IL-6, IL-8, PGE2, IL-17
which factors important in RA? Psoriasis?
RA = TNF, IL-1/IL-6
Psoriasis = lL-17
Pathologic effects characteristic of RA?
tends to be more peripheral joints
inflamed synovial membrane
cartilage in bone is broken down and soften
soft and spongey
Criteria for RA?
Need to have 4 out of 7
Morning stiffness 3 or more joints involved Arthritis of hand joints Symmetrical arthritis Rheumatoid nodules Positive serum rheumatoid factor Radiographic changes
Goal of Arthritis therapy
Improve & Maintain functional status to inc QOl
Control of disease activity and joint pain
Slow progression of disease activity and reduce deformities
improve extra-articular manifestations ( = outside joints)
Poor predictor of outcomes for RA
young age at time of dx Elevated ESR High titer of Rheumatoid factor Swelling founding > 20 joints Female Extra-articular manifestations
ARC 20
- Pt experiences a 20% improvement in tender joint count and swollen joint count
- Plus a > 20% improvement in at least 3 of 5 criteria…
Patient pain assess, global assess, physical global asses, self-asses, acute case reactant
40-50% of individuals with psoriatic arthritis have genotype for…
HLA-B27
Median onset of Psoriatic Arthritis?
30-50yrs old
Men/women effected equally
Oligoarticular Psoriatic Arthritis
70% of pts and is generally mild, and usually only involves fewer than 3 joints
Polyarticular Psoriatic Arthritis
25% of cases, and effects 5 or more joints on both side of the body simultaneously
most similar to RA and is disabling in ~ 50% of all cases
Arthritis mutilans Psoriatic Arthritis
Less than 5% and is severe, deforming and destructive
Spondyloarthritis Psoriatic Arthritis
Stiffness of the neck or sacroiliac joint of the spine
Distal interphalangeal predominant Psoriatic Arthritis
5% of pts, characterized by inflammation and stiffness in the joints nearest to the ends of fingers/toes
nail changes often marked
Psoriatic Arthritis treatment for core pain management
NSAIDs and COX-2 inhib
Psoriatic Arthritis drugs that are specifically for it
Stelara (Ustekinumab)
Otezla (Apremilast)
commonly used but not specifically for….Adalimumab, Entanercept
Non-Pharma Treatment for RA
Primary: OT/PT, Smoking cessation, Weight loss, Massage, Exercise
Secondary: Emotional support & ed, assistive devices, surgical procedures, mediterranean diet
Approach to RA treatment
Get aggressive early
- DMARD or Biologic agent + NSAID
- 2nd line Biologic agent
- Combining Biologica agents
Preferred ARC 2021 agents
DMARDs: Methotrexate
Which RA DMARDs cant be used together?
Leflunamaide & Methotrexate
Have same MOA
also -nibs/mabs can only use one at a time
Starting therapy for RA?
- Establish dx and evaluate severity
- Initiate therapy therapy ( TB screen, Vaccines, Patient Ed, pain control, OT/PT)
- periodically assess disease activity
Early RA w/ low disease activity and no poor prognosis factors therapy
DMARD monotherapy = preferred (MTX drug of choice, quicker onset and less toxicity)
If poor response after 3 months, can do either…
- add sulfasalazine or hydroxychloroquine
- anti-TNF agent or tofacitinib
Early RA w/ moderate to high disease activity and poor prognosis therapy
- DMARD monotherapy preferred
- biologic agent +/- methotrexate
- Triple therapy usually MTX, sulfasalazine, hydroxycholorquine
When should you re-assess pts in Early RA management?
3 months if inadequate response
6 months for Non-TNF biologics
Labs to check for drugs?
CBC, creatinine for Methotrexate and Sulfasalazine
Special Pops for RA
Hep B = no changes
Hep C = cant do biologics
Cancer (Melanoma) = DMARD > Biologic/Tofacitinib
Cancer (Treated solid tumor) = same as others
Cancer (Treated Lymphoma) = rituximab > non-TNF
CHF 3-4 = no anti-TNF rec
Latent TB = treat 1 month before starting biolgoic
Active TB = complete course for TB
Recommended Vaccinations prior to starting biologic therapy or a DMARD
Pneumococcal vaccine Influenza vaccine Hep B vaccine HPV *may be given before or concurrently with DMARD or biologic agent therapy
Herpes zoster = given before starting
NSAIDs, COX-II inhibitors, Salicylates Role in therapy & Efficacy
Role in therapy:
- Symptomatic tx of mild RA
- Doesn’t alter course of disease
- if no effect, add DMARD
- can be used with DMARD to manage until DMARD takes effect
Efficacy:
If no effect in 2-4 wks, inc dose or switch to another agent
COX non-specific
Ibuprofen
naproxen
indomethacin
COX-2 preferential
Etodolac
Diclofenac
Nabumetone
Meloxicam
COX-2 specific
Celecoxib, concern about inc CV risk
NSAIDs monitoring
SCr, CBC
BP, wt, electrolytes, stool color
NSAIDs toxicity
GI, renal,
Dont need to put everyone on PPI, only if at risk for GI bleeding
NSAID patient info
Take w/ food, report GI symptoms, black stools, SOB, edema, wt gain or dizziness
Salicylate specific = ringing in ears
Methotrexate MOA
Antimetabolite, inhibiting dihydrofolate reductase
Methotrexate Role in Therapy
Considered DMARD of choice & gold standard
Methotrexate Dosing
2.5mg po or IM q12hr X 3 doses per week
inc by 2.5mg per wk q6-8 weeks to max of 20-25mg/wk
Goal: atleast 15mg/wk by week 6-8, 20-25mg/week later
** Can give as 1 dose per week when tolerated **
If CrCl < 50, decrease dose by 50%
Methotrexate Efficacy
Most predictable long-term benefit
Onset of effect is 2-4 weeks
Methotrexate toxicity
GI = N/V/D, stomatitis Hematolgic Folic Acid deficiency = take FA to reduce GI tox Hepatic = inc LFTs, cirrhosis (rare) Pulmonary = fibrosis (rare) Teratogenic
Methotrexate monitoring
BL: LFTs, Hep B/C studies, CBC w plt, SCr
Every 1-2months: CBC w/ plt, AST, Albumin
Methotrexate Patient education
Counsel about weekly dosing
Ask about SOB, infections, GI symptoms, mouth sores
Methotrexate CI
Pregnancy Chronic liver disease Immunodeficiency CrCl < 10ml/min Effusion Leukopenia Thrombocytopenia
Leflunomide Dosing
Loading: 100mg QD X 3 days
Maintenance: 20mg QD, dec to 10mg if not tolerated
Leflunomide Role in Therapy
alternative in pts who fail or don’t tolerate MTX or sulfasalazine
can be used with NSAIDs or Steroids
Leflunomide notable Adverse effects
rare reports of hepatotoxicity, liver failure and death
Leflunoamide monitoring
LFTs at BL, Q month for 6 months, then Q6-8wk
IF 2-X ULN, dec to 10mg/day, if 3 X ULN = D/c
CBC & put at BL, monthly for 6 months, then Q6-8wk
Leflunoamide Patient education
maintain adequate hydration
report GI symptoms or jaundice
report signs/symptoms of infection
Hydroxychloroquine MOA
Antimalarial
Inhibit lysosome function leading to decreased immune function and TLR blockade
Hydroxychloroquine Role in therapy
Use in mild RA in pts who dont tolerate, respond or have CI for MTX
Hydroxychloroquine efficacy
up to -12 weeks to see effect, can take 6 months
Hydroxychloroquine Dosing
200mg sulfate = 155 mg base
200-300mg BID X 1-2 months, then dc to 200mg QD-BID (Max 400mg/day)
Hydroxychloroquine Toxicity
GI = N/V/D
Ocular = night blindness, loss of vision, retinal damage
Neurologic (mild) = headache, vertigo, insomnia
Dermatologic = inc skin pigment, rash, hair loss
Hydroxychloroquine monitoring
BL eye exam, then q 6-12 months
Hydroxychloroquine patient education
wear sunglasses in bright light = dec accommodation
caution night driving = dec night vision
report vision changes
take with food or milk
Sulfasalazine MOA
Production of 5-ASA, NF-kB inhibition
Sulfasalazine Role in Therapy
mild disease, women who plan to have children
Sulfasalazine efficacy
effects seen in 1-2 months
Sulfasalazine Dosing
500mg BID, inc to 1gm BID
Sulfasalazine Toxicity
Myelosuppresion
Rash
increased LFTs
GI
Sulfasalazine Monitoring
CBC w/ plt at BL & q wkly for 1 month, then q1-2 months
Tofacitinib Indications
Moderate to severe RA w/ inadequate response or intolerance to MTX
monotherapy or combo with MTX or other Non-biologic DMARDs
Tofacitinib Caution
Dont use w/ biologic DMARDs, Azathioprine or cyclosporine
Tofacitinib warnings (also relevant to other -inibs/ - imabs)
Serious infections
If serious infection develops, hold therapy until controlled
before starting, test for TB…treat TB prior to tarting, and monitor all pts for active TB during treatment
Avoid live vaccines during therapy
DI = CYP3A4
Upadacinitinib (Rinvoq) Indication & Dosing
15mg PO daily
PA after Anti-TNF agent
RA after prior anti-TNF agent
Upadacinitinib (Rinvoq) warning
Inc risk of thromboembolism
Higher rates of CV death, MI and Stroke vs other anti-TNF agents
Baracitinib Indication & Dosing
2mg PO daily
RA after prior anti-TNF therapy
Baracitinib (Olumiant) Warnings
Inc risk of thromboembolism
Myelosuppression
Common issues with Biologics
ADR: Serious infections Lymphoma and skin cancers Worsening CHF Neutropenia Hep B reactivation
Pt ed:
Updated vaccines before treatment
teach pt proper injection technique
Entanercept (Embrel) Role in Therapy
- used for refractory RA in pts with inadequate response to DMARDs
- approved for use early in disease
- cab be combo with MTX, steroids, or NSAIDs
Entanercept (Embrel) Dosage
25mg Sq twice weekly or 50mg once weekly
keep in fridge
Entanercept (Embrel) formulation
Sureclick
pre-filled syringe
Adalimumab (Humira) Dosing
40 mg SQ every other week, weekly if not on MTX
Adalimumab (Humira) Dosage forms
Prefilled syringes
Pen formulation
Adalimumab (Humira) Role in therapy
used in pts who had an inadequate response to 1 or more DMARDs
Adalimumab (Humira) ADR addition to typical
Headache & rash
Golimumab (Symphonic) Dosing
50mg SQ q monthly
Golimumab (Symphonic) toxicities
Upper resp tract infection
LFT increases
Hypertension
Injection site erythema
Certolizumab (Cizmia) dosing
400mg SQ every 4 weeks can be considered, dosed monthly
Certolizumab (Cizmia) Indication
monotherapy or combo with MTX
Certolizumab (Cizmia) Toxicity
Normal ones +
Upper resp tract infection
Hypertension
back pain
Infliximab (Remicade) Role in therapy
used in combo with MTX in pts who have had inadequate response to MTX alone
Infliximab (Remicade) Dosage
3mg/kg by IV infusion, q2wks/q6wks/q8wks
May inc to 10mg/kg, do Q 4 weeks
infuse over 2hrs
Infliximab (Remicade) ADR
URIs, headache, N, sinusitis, rash, cough
Other common issues listed
Neurologic = guillan barre
Dont give live vaccines
Abataceot (Orencia) Role in therapy
more second line
pts w/ moderate+severe RA who had inadequate response to 1 or more DMARDs or TNF-a
can be used as monotherapy or w/ DMARDs
* Dont give with TNF-a or anakinra
comes in prefilled syringe
Abataceot (Orencia) Dosing
most do 125mg Q weekly without loading dose
Abataceot (Orencia) Adverse effects
common symptoms listed
Headache, URIs, sore throat, nausea
Don’t take live vaccines during and 3 months after treatment
**COPD have inc respiratory symptoms
Tocilizumab (Actemra) MOA
IL-6 receptor inhib
Tocilizumab (Actemra) indication
RA pts who have inadequate response to atleast 1 DMARD
use w/ or w/o MTX
Tocilizumab (Actemra) Black Box warning
Risk for serious infections, TB reactivation/new infection, fungal infection
Tocilizumab (Actemra) Dosing
infusion
4mg/kg IV every 4 weeks
Rituximab Role în therapy
in combo w/ MTX in pts with moderate-severe RA with inadequate response to 1 or more TNF-a
Rituximab Dosing
1000mg IV X 2 doses 2 weeks apart
pretreat w/ 100mg methylprednisolone
Rituximab Adverse effects
infusion reactions, infections, arrhythmias, renal toxicity,bowel obstruction
CHF
Risk of Demylenating Syndrome
Anakinra (Kineret) Role in therapy
Dont use with TNF-a, not as effective as TNF-a
can be used alone or in combo
used in pts who have failed 1 or more DMARDs
Anakinra (Kineret) Dosing
not used much
100mg SQ QD
Anakinra (Kineret) Supplied
Prefileld syringes
Last resort for refractory patients?
Steroids
wants to add Vit D and Calcium therapy if choosing to do so
Corticosteroids Doses
PO = lowest dose possible < 10mg = low, >10mg = high dose
IA= no more than 2-3 shots/joint/yr
Corticosteroids Toxicity
HPA suppression
Myopathies
shit load
Corticosteroids Pt education
- report signs and symptoms of infection
- take Calcium and Vit D
- Regular opthalmologic exams
Corticosteroids monitoring
BP BG electrolytes IOP BMD
How to treat vasculitis?
Corticosteroids, NSAIDs
How to treat ocular issues from RA?
Artificial tears
Restasis
How to treat Sjogrens syndrome (Xerostomia) Dry mouth
Cevimeline 30mg po TD (Evoxac)
pilocarpine 5mg po QID (Salagan)
How to treat nodules from RA?
no treatments
