Lecture 9 - Rheumatoid Arthritis Flashcards
1
Q
Meds most effective for acute pain relief in RA?
A
NSAIDs
Ibuprofen, also prednisone
2
Q
Which meds have most risk of re-activating Hep B?
A
Rituximab, -mabs are immunosuppressive
3
Q
Which med required periodic eye exams for RA?
A
Hydroxychloroquine
4
Q
Med with highest risk for infections?
A
Etanercept
5
Q
Which RA med is safe for pregnancy?
A
sulfasalazine
6
Q
Meds most appropriate for someone with kerato-conjunvitis related to RA?
A
Restasis
7
Q
RA risks
A
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
8
Q
Some Interleukin and Cytokine factors for RA?
A
IL-1, TNF-a, IL-6, IL-8, PGE2, IL-17
9
Q
which factors important in RA? Psoriasis?
A
RA = TNF, IL-1/IL-6
Psoriasis = lL-17
10
Q
Pathologic effects characteristic of RA?
A
tends to be more peripheral joints
inflamed synovial membrane
cartilage in bone is broken down and soften
soft and spongey
11
Q
Criteria for RA?
A
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
12
Q
Goal of Arthritis therapy
A
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)
13
Q
Poor predictor of outcomes for RA
A
young age at time of dx Elevated ESR High titer of Rheumatoid factor Swelling founding > 20 joints Female Extra-articular manifestations
14
Q
ARC 20
A
- 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
15
Q
40-50% of individuals with psoriatic arthritis have genotype for…
A
HLA-B27
16
Q
Median onset of Psoriatic Arthritis?
A
30-50yrs old
Men/women effected equally
17
Q
Oligoarticular Psoriatic Arthritis
A
70% of pts and is generally mild, and usually only involves fewer than 3 joints
18
Q
Polyarticular Psoriatic Arthritis
A
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
19
Q
Arthritis mutilans Psoriatic Arthritis
A
Less than 5% and is severe, deforming and destructive
20
Q
Spondyloarthritis Psoriatic Arthritis
A
Stiffness of the neck or sacroiliac joint of the spine
21
Q
Distal interphalangeal predominant Psoriatic Arthritis
A
5% of pts, characterized by inflammation and stiffness in the joints nearest to the ends of fingers/toes
nail changes often marked
22
Q
Psoriatic Arthritis treatment for core pain management
A
NSAIDs and COX-2 inhib
23
Q
Psoriatic Arthritis drugs that are specifically for it
A
Stelara (Ustekinumab)
Otezla (Apremilast)
commonly used but not specifically for….Adalimumab, Entanercept
24
Q
Non-Pharma Treatment for RA
A
Primary: OT/PT, Smoking cessation, Weight loss, Massage, Exercise
Secondary: Emotional support & ed, assistive devices, surgical procedures, mediterranean diet
25
Approach to RA treatment
Get aggressive early
1. DMARD or Biologic agent + NSAID
2. 2nd line Biologic agent
3. Combining Biologica agents
26
Preferred ARC 2021 agents
DMARDs: Methotrexate
27
Which RA DMARDs cant be used together?
Leflunamaide & Methotrexate
Have same MOA
also -nibs/mabs can only use one at a time
28
Starting therapy for RA?
1. Establish dx and evaluate severity
2. Initiate therapy therapy ( TB screen, Vaccines, Patient Ed, pain control, OT/PT)
3. periodically assess disease activity
29
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...
1. add sulfasalazine or hydroxychloroquine
2. anti-TNF agent or tofacitinib
30
Early RA w/ moderate to high disease activity and poor prognosis therapy
1. DMARD monotherapy preferred
2. biologic agent +/- methotrexate
3. Triple therapy usually MTX, sulfasalazine, hydroxycholorquine
31
When should you re-assess pts in Early RA management?
3 months if inadequate response
6 months for Non-TNF biologics
32
Labs to check for drugs?
CBC, creatinine for Methotrexate and Sulfasalazine
33
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
34
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
35
NSAIDs, COX-II inhibitors, Salicylates Role in therapy & Efficacy
Role in therapy:
1. Symptomatic tx of mild RA
2. Doesn't alter course of disease
3. if no effect, add DMARD
4. 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
36
COX non-specific
Ibuprofen
naproxen
indomethacin
37
COX-2 preferential
Etodolac
Diclofenac
Nabumetone
Meloxicam
38
COX-2 specific
Celecoxib, concern about inc CV risk
39
NSAIDs monitoring
SCr, CBC
BP, wt, electrolytes, stool color
40
NSAIDs toxicity
GI, renal,
Dont need to put everyone on PPI, only if at risk for GI bleeding
41
NSAID patient info
Take w/ food, report GI symptoms, black stools, SOB, edema, wt gain or dizziness
Salicylate specific = ringing in ears
42
Methotrexate MOA
Antimetabolite, inhibiting dihydrofolate reductase
43
Methotrexate Role in Therapy
Considered DMARD of choice & gold standard
44
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%
45
Methotrexate Efficacy
Most predictable long-term benefit
| Onset of effect is 2-4 weeks
46
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
```
47
Methotrexate monitoring
BL: LFTs, Hep B/C studies, CBC w plt, SCr
Every 1-2months: CBC w/ plt, AST, Albumin
48
Methotrexate Patient education
Counsel about weekly dosing
Ask about SOB, infections, GI symptoms, mouth sores
49
Methotrexate CI
```
Pregnancy
Chronic liver disease
Immunodeficiency
CrCl < 10ml/min
Effusion
Leukopenia
Thrombocytopenia
```
50
Leflunomide Dosing
Loading: 100mg QD X 3 days
Maintenance: 20mg QD, dec to 10mg if not tolerated
51
Leflunomide Role in Therapy
alternative in pts who fail or don't tolerate MTX or sulfasalazine
can be used with NSAIDs or Steroids
52
Leflunomide notable Adverse effects
rare reports of hepatotoxicity, liver failure and death
53
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
54
Leflunoamide Patient education
maintain adequate hydration
report GI symptoms or jaundice
report signs/symptoms of infection
55
Hydroxychloroquine MOA
Antimalarial
| Inhibit lysosome function leading to decreased immune function and TLR blockade
56
Hydroxychloroquine Role in therapy
Use in mild RA in pts who dont tolerate, respond or have CI for MTX
57
Hydroxychloroquine efficacy
up to -12 weeks to see effect, can take 6 months
58
Hydroxychloroquine Dosing
200mg sulfate = 155 mg base
200-300mg BID X 1-2 months, then dc to 200mg QD-BID (Max 400mg/day)
59
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
60
Hydroxychloroquine monitoring
BL eye exam, then q 6-12 months
61
Hydroxychloroquine patient education
wear sunglasses in bright light = dec accommodation
caution night driving = dec night vision
report vision changes
take with food or milk
62
Sulfasalazine MOA
Production of 5-ASA, NF-kB inhibition
63
Sulfasalazine Role in Therapy
mild disease, women who plan to have children
64
Sulfasalazine efficacy
effects seen in 1-2 months
65
Sulfasalazine Dosing
500mg BID, inc to 1gm BID
66
Sulfasalazine Toxicity
Myelosuppresion
Rash
increased LFTs
GI
67
Sulfasalazine Monitoring
CBC w/ plt at BL & q wkly for 1 month, then q1-2 months
68
Tofacitinib Indications
Moderate to severe RA w/ inadequate response or intolerance to MTX
monotherapy or combo with MTX or other Non-biologic DMARDs
69
Tofacitinib Caution
Dont use w/ biologic DMARDs, Azathioprine or cyclosporine
70
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
71
Upadacinitinib (Rinvoq) Indication & Dosing
15mg PO daily
PA after Anti-TNF agent
RA after prior anti-TNF agent
72
Upadacinitinib (Rinvoq) warning
Inc risk of thromboembolism
Higher rates of CV death, MI and Stroke vs other anti-TNF agents
73
Baracitinib Indication & Dosing
2mg PO daily
RA after prior anti-TNF therapy
74
Baracitinib (Olumiant) Warnings
Inc risk of thromboembolism
| Myelosuppression
75
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
76
Entanercept (Embrel) Role in Therapy
1. used for refractory RA in pts with inadequate response to DMARDs
2. approved for use early in disease
3. cab be combo with MTX, steroids, or NSAIDs
77
Entanercept (Embrel) Dosage
25mg Sq twice weekly or 50mg once weekly
keep in fridge
78
Entanercept (Embrel) formulation
Sureclick
| pre-filled syringe
79
Adalimumab (Humira) Dosing
40 mg SQ every other week, weekly if not on MTX
80
Adalimumab (Humira) Dosage forms
Prefilled syringes
| Pen formulation
81
Adalimumab (Humira) Role in therapy
used in pts who had an inadequate response to 1 or more DMARDs
82
Adalimumab (Humira) ADR addition to typical
Headache & rash
83
Golimumab (Symphonic) Dosing
50mg SQ q monthly
84
Golimumab (Symphonic) toxicities
Upper resp tract infection
LFT increases
Hypertension
Injection site erythema
85
Certolizumab (Cizmia) dosing
400mg SQ every 4 weeks can be considered, dosed monthly
86
Certolizumab (Cizmia) Indication
monotherapy or combo with MTX
87
Certolizumab (Cizmia) Toxicity
Normal ones +
Upper resp tract infection
Hypertension
back pain
88
Infliximab (Remicade) Role in therapy
used in combo with MTX in pts who have had inadequate response to MTX alone
89
Infliximab (Remicade) Dosage
3mg/kg by IV infusion, q2wks/q6wks/q8wks
May inc to 10mg/kg, do Q 4 weeks
infuse over 2hrs
90
Infliximab (Remicade) ADR
URIs, headache, N, sinusitis, rash, cough
Other common issues listed
Neurologic = guillan barre
*Dont give live vaccines*
91
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
92
Abataceot (Orencia) Dosing
most do 125mg Q weekly without loading dose
93
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
94
Tocilizumab (Actemra) MOA
IL-6 receptor inhib
95
Tocilizumab (Actemra) indication
RA pts who have inadequate response to atleast 1 DMARD
use w/ or w/o MTX
96
Tocilizumab (Actemra) Black Box warning
Risk for serious infections, TB reactivation/new infection, fungal infection
97
Tocilizumab (Actemra) Dosing
infusion
4mg/kg IV every 4 weeks
98
Rituximab Role în therapy
in combo w/ MTX in pts with moderate-severe RA with inadequate response to 1 or more TNF-a
99
Rituximab Dosing
1000mg IV X 2 doses 2 weeks apart
pretreat w/ 100mg methylprednisolone
100
Rituximab Adverse effects
infusion reactions, infections, arrhythmias, renal toxicity,bowel obstruction
CHF
Risk of Demylenating Syndrome
101
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
102
Anakinra (Kineret) Dosing
not used much
100mg SQ QD
103
Anakinra (Kineret) Supplied
Prefileld syringes
104
Last resort for refractory patients?
Steroids
wants to add Vit D and Calcium therapy if choosing to do so
105
Corticosteroids Doses
PO = lowest dose possible < 10mg = low, >10mg = high dose
IA= no more than 2-3 shots/joint/yr
106
Corticosteroids Toxicity
HPA suppression
Myopathies
shit load
107
Corticosteroids Pt education
1. report signs and symptoms of infection
2. take Calcium and Vit D
3. Regular opthalmologic exams
108
Corticosteroids monitoring
```
BP
BG
electrolytes
IOP
BMD
```
109
How to treat vasculitis?
Corticosteroids, NSAIDs
110
How to treat ocular issues from RA?
Artificial tears
| Restasis
111
How to treat Sjogrens syndrome (Xerostomia) Dry mouth
Cevimeline 30mg po TD (Evoxac)
| pilocarpine 5mg po QID (Salagan)
112
How to treat nodules from RA?
no treatments
