Rheumatoid Arthritis Flashcards
1
Q
What is rheumatoid arthritis?
A
an autoimmune condition leading to inappropriate immune system activity causing synovial and connective tissue inflammation
-chronic inflammation–>growth of tissue (pannus)–>cartilage and bone loss
-triggered by genetics and a “stochastic” event
2
Q
What are the consequences of inflammation due to rheumatoid arthritis?
A
loss of cartilage
formation of scar tissue
ligament laxity
tendon contractures
3
Q
Which sex is rheumatoid arthritis more common in?
A
women (earlier onset as well)
-occurs at any age
-no difference with ethnicity
4
Q
What are the symptoms of rheumatoid arthritis?
A
symmetrical joint pain and stiffness > 6 weeks
muscle pain
may have fatigue, low-grade fever, decreased appetite, weakness
joint tenderness with warmth + swelling
rheumatoid nodules may develop
5
Q
What is the typical presentation of a new case of rheumatoid arthritis?
A
rapid onset starting in peripheral joints
6
Q
Differentiate OA and RA.
A
age of onset:
-RA: any
-OA: later in life
speed of onset:
-RA: fast
-OA: slow
joint symptoms:
-RA: painful, swollen, stiff
-OA: painful; little swelling
systemic symptoms:
-RA: yes, especially during flares
-OA: none
affected joints:
-RA: symmetrical
-OA: often starts unilateral, weight bearing joints mainly
duration of morning stiffness:
-RA: >1hr duration
-OA: <1hr duration, stiffness returns end of day or activity
7
Q
Describe the joint damage caused by rheumatoid arthritis.
A
occurs early in the course of RA
30% have bone erosion at time of diagnosis
damage is irreversible
functional loss follows
8
Q
What is the extraarticular sequelae of rheumatoid arthritis?
A
blood vessels
eyes
lungs
heart
skin
hematologic
muscle
bone
9
Q
Describe the impacts that rheumatoid arthritis can have on blood vessels.
A
rheumatoid vasculitis (autoimmune)
can affect any blood vessel (sx depend on affected vessel)
occurs with severe, long-standing RA
substantial morbidity
only tx: aggressive tx of RA
10
Q
Describe the impacts that rheumatoid arthritis can have on the lungs.
A
pleuritis, pleural effusion, fibrosis, pulmonary nodules
drugs used to treat RA can impact lung function
11
Q
Describe the impacts that rheumatoid arthritis can have on the eyes.
A
periscleritis, scleritis, uveitis, iritis
painful, visual acuity loss
12
Q
Describe the impacts that rheumatoid arthritis can have on the heart.
A
pericarditis, myocarditis
increased risk of CAD, HF, afib
13
Q
Describe the impacts that rheumatoid arthritis can have on muscle.
A
generalized muscle weakness and pain
from synovial inflammation, myositis, vasculitis
steroid-induced
14
Q
Describe the impacts that rheumatoid arthritis can have on the bone.
A
osteopenia is common
local bone loss around affected joints
15
Q
Describe the impacts that rheumatoid arthritis can have on the skin.
A
rheumatoid nodules
ulcers
steroid-induced
16
Q
Describe the impacts that rheumatoid arthritis can have on hematology.
A
anemia of chronic disease
17
Q
How is rheumatoid arthritis diagnosed?
A
cannot be established by a single lab test or procedure
established diagnostic criteria/scoring system:
-joint involvement
-lab tests: rheumatoid factors, elevated ESR + CRP, anti-CCP
-duration of symptoms
18
Q
What are the goals of therapy for rheumatoid arthritis?
A
prevent and control joint damage
improve QoL
prevent loss of function
decrease pain
achieve remission or low disease activity
-tender/swollen joint count < 1
-measure function based on HAQ
-physical global assessment < 2
-CRP score < 1
-PtGA < 2 **
19
Q
What are the principles of management for rheumatoid arthritis?
A
- early recognition + diagnosis
-significant damage in first two years of disease - early use of DMARDs
-start within 3 months of diagnosis
-depending on severity, treat aggressively - concept of “tight control”
-treat until remission or low disease severity
-quickly treat exacerbations
-add DMARDs or early switch
-adjunct NSAIDs/steroids - responsible NSAID and steroid use
-reduce/dc as disease enters remission
20
Q
What are the non-pharmacological therapies for rheumatoid arthritis?
A
education
rest is important, balance with activity
reduce joint stress with RA friendly tools
occupational and physical therapy
diet/weight loss
surgery
21
Q
What are the classes of treatment for rheumatoid arthritis?
A
maintenance:
-tDMARDs
-biologic DMARDs
-synthetic DMARDs
flares:
-steroids
-NSAIDs/analgesia
22
Q
What are examples of tDMARDs?
A
hydroxychloroquine
sulfasalazine
methotrexate
leflunomide
23
Q
What are the benefits of tDMARDs?
A
controls symptoms
delay or stop progression of disease
24
Q
True or false: tDMARDs do not require regular monitoring
A
false
25
What is the MOA of the different tDMARDs?
hydroxychloroquine:
-inhibits neutrophils and chemotaxis
-impairs complement system
sulfasalazine:
-prodrug metabolized into 5-ASA and sulfapyridine
-modulates inflammatory mediators
methotrexate:
-anti folate=less DNA synthesis, repair, replication and immune respinse
leflunomide:
-inhibits pyrimidine synthesis = anti-inflamm.
26
What is the onset of the tDMARDs?
hydroxychloroquine: 2-6 months
sulfasalazine: 2-3 months
methotrexate: 1-2 months
leflunomide: 1-3 months
27
What is the dosing of methotrexate?
7.5-25mg po weekly
-titrate to target in most cases
-renal dosing: 10-50ml
-may initiate at target dose in select pts
28
What are the common adverse effects of hydroxycholoroquine?
best tolerated DMARD
NVD, cramps
skin/allergic reactions
HA, dizziness
29
What are the common adverse effects of sulfasalazine?
HA
NVD
photosensitivity
30
What are the common adverse effects of leflunomide?
nausea, diarrhea
rash and HTN
reversible alopecia
31
What are the common adverse effects of methotrexate?
NV
fatigue
stomatitis
photosensitivity
hair loss
skin itch/burning/rash
32
What some strategies to manage the adverse effects of methotrexate?
folic acid 1-5mg/d or 5-10mg once weekly
split dosing on the same day
SC for GI side effects
add a PPI for 3 days
33
What are the serious adverse effects of the tDMARDs?
hydroxychloroquine:
-myopathy, ocular toxicity
sulfasalazine:
-hematologic
methotrexate:
-hepatotoxicity, hematologic, pulmonary toxicity, infection increase, reversible sterility in men
leflunomide:
-hepatotoxicity, infection increase, weight loss
34
What are the contraindications to the tDMARDs?
hydroxychloroquine:
-pre-existing retinopathy
sulfasalazine:
-hypersensitivity to salicylates or sulfonamides, asthma attack precipitated by ASA or NSAID, GI ulcer, severe renal/hepatic impairment
methotrexate:
-caution in lung dysfunction, pregnancy/breastfeeding, hematologic abnorm, severe hepatic impairment
leflunomide:
-mod to severe renal/hepatic impairment, pregnant/breastfeeding, hematologic abnorm, infection
35
What are the drug interactions of the tDMARDs?
-not including MTX
hydroxychloroquine:
-no CYP interactions, high risk of QT prolongation
sulfasalazine:
-nausea with MTX, warfarin
leflunomide:
-bile acid sequestrants (elimination), immunosuppression, live vaccines
36
What are the drug interactions of methotrexate?
NSAIDs: decrease clearance of MTX
-<15mg/week: likely no risk
-15-25mg/week: very low risk
-risk increases with renal dysfunction
trimethoprim: contraindicated
PPIs: issue if MTX > 500mg/wk
loop diuretics: decrease clearance of MTX, issue if high dose
live vaccines
37
How can we monitor tDMARDs for efficacy?
disease activity (ESR, CRP) q1-3 months initially
radiographs q6-12 months
patient assessment
38
How can we monitor tDMARDs for safety?
hydroxychloroquine:
-no labs, ophthalmic exam baseline and q5yrs
sulfasalazine:
-CBC, LFT, SCr
methotrexate:
-CBC, LFT, SCr, CXR (baseline)
leflunomide:
-CBC, LFT, SCr
39
What is the relative potencies of the tDMARDs?
MTX=leflunomide > SSZ > HCQ
40
Which tDMARDs show "healing" of bone?
methotrexate
leflunomide
41
Which tDMARDs are considered less effective?
hydroxychloroquine and sulfasalazine
*less effective vs other DMARDs*
42
What is the place in therapy for each tDMARD?
hydroxychloroquine:
-mild + early RA, best tolerated, combo
sulfasalazine:
-not tolerating others, most effective earlier, combo
methotrexate: standard therapy
-highly effective in mod-severe dx, increase efficacy with biologics
leflunomide:
-MTX not tolerated, added in low doses to MTX
43
What is central to the inflammatory process of rheumatoid arthritis?
monocytes, macrophages, and fibroblasts within the synovium which produce cytokines: TNF-a and IL
-over time these damage soft tissue and bone
-B and T cells also a target
44
What are the main classes of biologic DMARDs?
TNF-a inhibitors
IL 1 or 6 inhibitors
T-cell co-stimulation inhibitors
B-cell depletors
45
What are the common adverse effects of all biologics?
nausea
diarrhea
headache
malaise
46
What are concerns for all biologics?
injection site rxn
infection rate increase
neutropenia
malignant disease
antibody development
47
Describe the concern regarding infection rate with biologics.
age and dose related
common: URTI, fungal, pneumonia
serious: Hep B/C, zoster, TB, etc
risk highest early in therapy
48
How can we mitigate the increased infection rate associated with biologics?
screen for serious infections prior to therapy
up to date on vaccinations
use biologics with shorter dosing interval if high risk
educate on signs of infection
never combine two biologics
49
Which biologic might be the safest option in patients at high risk of infection?
abatecept
50
What should be done if infection occurs while on a biologic?
consider temporary d/c
51
Describe the risk of neutropenia that is common with all biologics.
~20% will experience a decrease
increases severity of infections
monitoring important
not a reason to d/c therapy
52
Describe the risk of malignancy that is common with all biologics.
overall: no cancer risk increases except for: skin and lymphomas
avoid biologics in those active malignancies
preferentially avoid if previous skin cancer
use rituximab if previous lymphoma
53
What occurs when there is antibody development to a biologic?
clearance of drug increased by body's defenses
-usually occurs within 2-6 months of starting
54
Which TNF-a inhibitor has the highest risk of antibody development? Which have lower risk?
higher risk: infliximab
lower risk: etanercept, adalimumab
55
Which drug can lower formation of antibodies to biologics?
methotrexate
56
True or false: antibody development does not occur with Il-6 inhibitors
true
57
What is the risk of antibody development with B and T cell inhibitors?
possible risk, less than TNF-inhibitors
58
What are examples of TNF-a inhibitors?
adalimumab
golimumab
certolizumab
infliximab
etanercept
59
Why is TNF-a one of the targets in rheumatoid arthritis with biologic drugs?
high TNF-a in RA patients --> bone erosion
60
What is the onset for TNF-a inhibitors?
within weeks
61
Describe the efficacy of TNF-a inhibitors?
ACR50 ~40%
combo with MTX = more effective
slow/stop radiographic progression
62
Which TNF-a inhibitors are only indicated in combination with MTX?
infliximab
golimumab
63
Which TNF-a inhibitor is administered IV?
infliximab (maybe golimumab)
-rest are SC
64
How frequently are TNF-a inhibitors administered?
mainly q2wks
65
What is an area that TNF-a inhibitors lack data in and therefore should be avoided?
renal impairment
66
True or false: TNF-a inhibitors are safe in pregnancy/breastfeeding
true
67
What are the contraindications to TNF-a inhibitors?
active severe infection
mod-severe HF
68
What are the drug interactions of TNF-a inhibitors?
live vaccines
additive immunosuppression
69
What are the adverse effects of TNF-a inhibitors?
liver enzyme elevations
HF (unique concern)
cutaneous (unique concern + rituximab)
autoimmune disease (unique concern)
seizure risk (unique concern)
70
When are we concerned about liver enzyme elevations with TNF-a inhibitors?
> 5x ULN (monitor periodically)
71
Describe HF as a unique concern for TNF-a inhibitors.
evidence is not conclusive
may cause or worsen HF
use cautiously if needed
utilize low doses
72
Describe cutaneous AEs as a unique concern for TNF-a inhibitors and rituximab.
increased risk of:
-cellulitis
-autoimmune skin disease
-malignancy
73
True or false: TNF-a inhibitors are an appropriate therapy if the patient has a seizure disorder
false
74
What are some monitoring parameters for TNF-a inhibitors?
TB, HIV, Hep B/C screening
CBCs
LFTs
signs of infection
ensure vaccinated
75
What is the MOA of IL inhibitors?
antagonize interleukin receptors --> decreased cytokine activity
76
What are examples of IL inhibitors?
anakinra (IL-1)
tocilizumab (Il-6)
sarilumab (IL-6)
77
What is the onset of IL inhibitors?
weeks but peak at 5-6 months
78
What are the contraindications to IL inhibitors?
anakinra: none
tocilizumab: active infection
sarilumab: none
79
What is the efficacy of the IL inhibitors?
anakinra:
-less anti-inflammatory than other biologics
-likely less effective than other biologics
-40% achieve ACR20
tocilizumab/sarilumab:
-~40% achieve ACR50
-similar or potentially more effective than TNF inhibitors
80
What is the route and admin and dosing frequency of the IL inhibitors?
anakinra: SC daily
tocilizumab: IV q4wks
sarilumab: SC q2wks
81
Which class of biologics has the robust data for renal impairment?
IL inhibitors
82
What are the adverse effects of the IL inhibitors?
anakinra:
-injection site rxns and infection
-serious AE risk similar to placebo
tocilizumab/sarilumab:
-GI perforation (unique + rituximab): caution if GI risk
-dyslipidemia (unique): increased TC/TG and decreased HDL
-HTN
-Ab development not linked to decreased efficacy (unique)
-others similar to TNF-a inhibitors
83
What are the drug interactions of IL inhibitors?
all:
-decreased IL-1/6 = increased CYP activity
-live vaccines
-additive immunosuppression
tocilizumab:
-increased simvastatin 4-10x
84
What are the monitoring parameters for the IL inhibitors?
anakinra:
-baseline CBCs, LFTs, SCr then q3-6mo
tocilizumab/sarilumab:
-baseline CBCs, LFTs, SCr then 4-8wks then q3-6mo
-lipids
-BP
-latent/active TB, HepB/C screening
85
What is the MOA of T cell co-stimulation inhibitors?
inhibit T cell activity
86
What is the use for T cell co-stimulation inhibitors?
inadequate response to DMARDs or TNF inhibitors
-monotherapy or combo with DMARD (MTX)
87
What is an example of a T cell co-stimulation inhibitor?
abatecept
88
What is the route of administration and frequency for abatecept?
optional IV loading dose
then SC once weekly
89
What are the adverse effects of abatecept?
similar to TNF inhibitors
COPD exacerbations (unique)
no impact on liver function (unique)
HTN
increased blood glucose
unknown if Ab impact efficacy or safety
90
What are the monitoring parameters for abatecept?
signs and symptoms of infection
TB and hepatitis
SCr, CBCs
blood pressure
blood glucose
91
What is the MOA of B-cell depletors?
bind B-cells and cause lysis
-B cells central to immune memory and Ab production
92
What is an example of a B-cell depletor?
rituximab
93
What is the efficacy of rituximab?
ACR50 of 43%
does not work well in RF-negative pts
no halt of radiographic progression
94
What is the route of admin and frequency for rituximab?
2 dose course: 1g IV 2 wks apart
-pretreat: methyprednisolone, dph, acet
-retreat when needed (~6 months)
-withhold HTN meds the morning of infusion
95
What are the adverse effects of rituximab?
infusion rxn more rapid, but mild + brief
initial infection rate non-existent, increases with rpt course
HTN
increased BG
GI perforation
cutaneous rxn (more common than other biologics)
Ab formation = increased rxns, decreased efficacy1
96
What are the monitoring parameters for rituximab?
CBC, SCr, LFT
TB, Hep B/C screening
97
What is the place in therapy for the biologic DMARDs?
considered once other options have been tried
-exception: initial severe RA
TNF inhibitors:
-initial biologic of choice for most
IL-1/6 inhibitors:
-anakinra: risk averse or cannot tolerate other DMARDs
-tocilizumab/sarilumab: mod-severe RA, combo with MTX
-both: Ab develop to other biologics
T-cell co-stimulation inhibitors:
-tDMARDs or TNF inhibitors failed
B-cell depletors:
-combo with MTX when others failed
-history of lymphoma
98
What is the MOA of JAK inhibitors?
JAK is a group of enzymes responsible for IL signaling
99
How should JAK inhibitors be taken?
preferably in combo with MTX
-may be used alone if MTX intolerance
-no other combos recommended
100
What is the place in therapy for JAK inhibitors?
last line
101
What are examples of JAK inhibitors?
tofacitinib
upadacitinib
baracitinib
102
What is the route of admin and frequency for JAK inhibitors?
po
OD or BID
103
What is the efficacy of JAK inhibitors?
combo: ACR50 46%
alone: ACR50 38%
104
What are the adverse effects of JAK inhibitors?
similar to TNF-inhibitors and other biologics:
-HTN
-LFTs/hepatotoxicity
-infections
-bradycardia
-GI perforation
*no concern about Ab development*
105
What is a contraindication to JAK inhibitors?
severe infection
105
What is the main drawback of JAK inhibitors?
CV risk (MI, clots)
malignancy
106
What are the drug interactions of JAK inhibitors?
tofacitinib/upadacitinib: major 3A4 substrate
live vaccines
immunosuppression
107
What are the monitoring parameters for JAK inhibitors?
CBC
LFT
lipids
TB testing
108
True or false: there is lots of data supporting JAK inhibitor use in pregnancy/breastfeeding
false
lacking data
109
What is an important tool in rheumatoid arthritis treatment?
corticosteroids
-most will use in course of disease
-likely has DMARD properties, and decreases early progression of RA
110
What are the three treatment modalities with corticosteroids for rheumatoid arthritis?
1. short-term use
-10-15mg prednisone equivalent/day
-taper and dc as sx improve
-limited safety issues if dose/duration kept low
2. chronic use
-5-10mg prednisone equivalent/day
-safety issues become apparent
-increased need for monitoring and adjunct treatment
3. pulse therapy
-high doses for a few days
-safety: CV collapse, hypokalemia, MI, severe infection
-last resort in RA
110
What is the onset of corticosteroids?
within days
110
What is the efficacy of corticosteroids for rheumatoid arthritis?
reduces joint tenderness more than NSAIDs and placebo
reduces pain more than NSAIDs
improves QoL measures
small radiographic progression decrease
*main benefit: subjective symptomatic improvement*
111
What are the monitoring parameters for corticosteroids?
long-term AEs
-glaucoma
-hyperglycemia
-dyslipidemia
-osteoporosis
-weight gain
112
Describe intra-articular corticosteroid injections for rheumatoid arthritis.
safe and effective when done by MD
effects are dramatic but temporary
same joint should not be done more than 3 months
rest joint x 3 days post-injection
issues: tendon rupture, synovitis, septic arthritis
113
What is the guideline approach to corticosteroid use in rheumatoid arthritis?
consider for flares or bridging
aim for max dose of 10mg/d
never use as monotherapy
consider avoiding if risk of steroid AE
114
What is the use of NSAIDs for rheumatoid arthritis?
provide high dose NSAIDs at initial diagnosis
use for at least 2 wks for maximum benefit
cautiously combine with other tx
consider providing GI protection
should not need to use chronically
115
What is the role of acetaminophen in rheumatoid arthritis?
sometimes added
-poor efficacy
116
What is the role of opioids in rheumatoid arthritis?
avoid
-limited evidence
-proper DMARD and non-pharm = greater benefit
117
What is tDMARD double therapy? Triple therapy?
double therapy: any two of MTX, SSZ, HCQ, SSZ
triple therapy: MTX + SSZ + HCQ
118
In general, how can we manage a rheumatoid arthritis flare?
intraarticular glucocorticoid if few joints
initiate/increase glucocorticoid
consider increasing DMARD dose
add new DMARD if frequent flares
119
As per the 2023 CRA guidelines, what is recommended regarding biologic or synthetic DMARDs for patients in remission or low disease activity?
remission: 6 months
reduce dose in stepwise manner but dont d/c
120
As per the 2023 CRA guidelines, what is recommended for people who fail to respond to TNF inhibitors?
different TNF inhibitor
non-TNF inhibitor biologic
JAK inhibitor
121
What is the recommendation from the ACR regarding DMARD tapering/dc?
recommend staying on DMARDs at current doses
-only consider taper if pt will remain on therapeutic dose of at least 1 DMARD, AND has been in remission x 6 months
122
When should therapy be escalated for rheumatoid arthritis?
failure to achieve remission or acceptable disease activity after 3-6 months at optimal dose
inability to taper steroids
recurrent flares
disease progression on xray
123
What are the recommendations for pre-conception in rheumatoid arthritis?
must dc unsafe meds
-MTX: male and female - stop 3 months prior
-leflunomide: male and female
achieve remission on safe options
-HCG and SSZ
-all biologics except: rituximab
-certolizumab has most robust data
124
What are the recommendations for peri-pregnancy in rheumatoid arthritis?
steroids can be used sparingly
ensure folic acid 5mg/d if previous MTX use
cautious use of NSAIDs
125
What are the recommendations for post-partum in rheumatoid arthritis?
flares are common
return to pre-pregnancy dose if compatible with breastfeeding
126
Which agents can be used for rheumatoid arthritis during lactation?
NSAIDs (ibuprofen preferred)
low dose steroids (<20mg prednisone per day)
SSZ and HCQ
TNF and IL-6 inhibitors
127
Which rheumatoid arthritis agents should be avoided during lactation?
MTX and LEF
