Rheumatoid Arthritis Flashcards
(136 cards)
1
Q
Compare RA and osteoarthritis.
Age
Speed of onset
Joint Sx
Affected Joints
Suration of Morning Stiffness
Presenece of systemic sx
A
Symmetrical joint pain and stiffness >6 weeks
1
Q
What are the goals of tx for RA?
A
Prevent and control joint damage
Prevent loss of function
Maintain QoL
Decrease pain
ACHIEVE REMISSION OR LOW DX ACTIVITY
2
Q
How can remission or low disease activity be defined in RA?
A
Tender/swollen joint count <1
A measure of function based on the Health Assessment Questionnaire (HAQ)
CRP score <1
A physician global assessment <2
A patient assessment of global disease activity (PtGA) <2 – considering how much it effects there QOL
3
Q
General Principles of RA Management
A
1) Early recognition and diagnosis
Significant damage occurs in first two years of disease
2) Early use of DMARDs
Start within 3m of diagnosis
Depending on severity, treat aggressively
3) Concept of “tight control”
Treat until remission or low disease activity
Quickly treat exacerbations
Aggressively add DMARDs or early switch
Adjunct NSAID / steroids
Frequent reassessment
4) Responsible NSAID and glucocorticoid use
Reduce / discontinue as disease enters remission
4
Q
What are some non-pharamcologic therapy for RA?
A
Patient education
Rest important, but balance with activity
Reduce joint stress with RA friendly tools
Occupational and physical therapy
Diet / weight loss
Surgery
5
Q
TX Classes for RA
A
6
Q
Use of DMARDS (traditional)
A
Slow onset of action
Controls symptoms
May delay or stop progression of disease
Requires regular monitoring
7
Q
What is a major downfall of DMARDS? How can this be overcome to prevent damage?
A
Slow onset of action
Offer Bridging Therapy
8
Q
What are some examples of traditional DMARDS?
A
Hydroxychloroquine
Sulfasalazine
Methotrexate
Leflunomide
Others: D-penicillamine, gold, azathioprine, cyclosporine, minocycline
9
Q
MOA of Hydroxyxhloroquine
A
Inhibits neutrophils and chemotaxis; impairs complement system
(down stream effects of inflammatory response)
10
Q
MOA of Sufazaline
A
Prodrug metabolized into 5-ASA and sulfapyridine
Modulates mediators of inflammatory response; may inhibit TNF
Immune system
11
Q
Methotrexate MOA
A
Anti-folate –> less DNA synthesis, repair, cellular replication and immune response
Often supplement with folic acid
12
Q
Leflunomid MOA
A
Inhibits pyrimidine synthesis, leading to anti-inflammatory effects
Modulates many signaling pathways
13
Q
Which DMARD’s are considered immunosupressant? Why is this a concern? Recommendation?
A
Issues with immune suppression, infx rate increase and vaccine – worry with methotrexate and leflunomide as immunosuppressant
14
Q
When is methotrexate considered immunosuppressive?
A
Methotrexate only considered immunosuppressant when at higher doses (25 mg)
15
Q
Onset of DMARDS
A
Hydroxychloroquine – 2-6 months
Sulfasalazine - 2-3 months
Methotrexate – 1-2 months
Leflunomide – 1-3 months
16
Q
Methotrexate DOSE
A
Methotrexate – 7.5 to 25mg PO weekly
Titrate to target in most cases
Renal dosing: eGFR 10 – 50ml
May initiate at target dose in select patients
17
Q
Methotrexate Minimal Target? Is it advanategous to go beyond top target dose?
A
Minimum Target Dose: 15 mg per week – better outcomes at 25 mg per week – dose ceiling effect beyond 25
18
Q
Methotrexate Dosage Forms. Issues/Benefits?
A
IM or Sub-cut is an option – oral – more adherence, conveince
Su-cut – slightly more potent (small increase in efficacy), less nausea, vomiting, diarhhea
19
Q
Who can be started at a high target dose of methotrexate? Advantage?
A
Select – start right at dose – no comorbidities and accepting of potential s/e
Advantage; faster onst and start slowing dx faster
20
Q
Titration of methotrexate? Dialysis?
A
Titration:
Average: 7.5 mg per week and increase by 2.5-5 Q 1 month
Can be used in dialysis – reduce all the numbers by 50% (including titration)
CrCl 10-50 mL/min: reduce dose 50% (including titration)
21
Q
S/e of Hydroxychloroquine
A
Best tolerated of the DMARDs
NVD, stomach cramps
Skin / allergic lesions (10%)
Headaches, dizziness
22
Q
S/e Sufazaline
A
Headache
Photosensitivity
NVD
23
Q
S/E Leflunoamide
A
Nausea/diarrhea – 60% of pts d/c because of this
Rash and hypertension
Reversible alopecia
24
Common S/e of Methotrexate
Nausea / vomiting*
Fatigue*
Stomatitis*
Photosensitivity
Hair loss
Skin itch / burning / rash
25
Strategies to manage methotrexate side effects? What side effects?
Only works on the side effects:
Nausea / vomiting*
Fatigue*
Stomatitis*
No counteraction between folic acid on same day as methotrexate – does not reduce how well methotrexate works
25 mg per week – need to take in same day – 12.5 mg in morning and 12.5 mg at night
26
Serious Side Effects of Hydroxychloroquine
Myopathy
Ocular toxicity – metabolites deposit n eye, long time (1000 mg cumulative dose) – baseline then every year
27
Serious Side Effects of Sufalazaline
Hematologic abnormalities – RBC, platelet decrease
28
Serious Side Effects of Methotrexate
Hepatotoxicity
Hematologic abnormalities
Pulmonary toxicity
Reversible sterility in men
Infection increase – URTI’s, more serious is pneumonia
29
Serious Side Effects of Leflunomaide
Hepatotoxicity
Significant weight loss
Infection increase
30
Methotrexate Monitoring
CBC
Liver panel (LFT's) baseline and yearly
SCr
Baseline --> Q2-4wks for first 3 months, then q3 months (draw labs 1-2d before next dose)
Chest X-ray (baseline)
31
Hydroxychloroquine C.I.
Pre-existing retinopathy
32
Sufazaline C.I.
Hypersensitivity to salicylates or sulfonamides
Asthma attacks precipitated by ASA or NSAIDs
Severe renal / hepatic impairment
Existing gastric or duodenal ulcer
33
Methotrexate C.I. and Cuations
Precaution/caution in lung dysfunction
C.I.:
Severe hepatic impairment
Current hematologic abnormalities
Pregnancy / breastfeeding
34
C.I. of Leflunomide
Moderate-severe renal (<60ml/min) / hepatic impairment
Current hematologic abnormalities or serious infection
Pregnancy / breastfeeding
35
Hydroxychloroquine D.I.
What can it cause and what drugs would be cautioned?
No CYP interactions
High risk QT-prolongation
36
Sulfasalazine D.I.
Additive nausea if used with MTX
Possible issue with Warfarin (↑ or ↓ INR)
37
Lefluomide D.I.
Bile-acid sequestrants cause rapid elimination – e.g. cholestyramine – can give to increase elimination
Additive immunosuppression – can combine with other immunosuppressant
Live vaccines
38
Drug Interactions of Methotrexate
Many drug interactions only significant based on cancer doses (e.g. 500 - 2000mg weekly)
NSAIDs
Decreases clearance of MTX, increased toxicity potential
MTX <15mg/week – likely no risk
MTX 15-25mg/week – very low risk
Risk increases with concomitant renal dysfunction
Trimethoprim (mono agent or in combination with sulfamethoxazole)
Significantly increases risk of pancytopenia at any MTX dose, consider contraindicated
PPIs
Only an issue if MTX >500mg/week (anti-cancer doses)
Loop diuretics
Decreases clearance of MTX, may increase nephrotoxicity potential
Likely only an issue on high doses
Live vaccines
39
What are the only pain medications that can be used when on methotrexate?
NSAID’s are only pain meds that can be used (acet can cause liver dysfx)
- Methotrexate doses when using cancer doses - really high drug interaction
40
How can one monitor the efficacy of DMARD's?
Disease activity (ESR, CRP) every 1-3 months initially
Radiographs every 6-12m
Patient assessment:
Chronic disease activity index - administered by HCP:
Health Assessment Questionnaire (HAQ) – done by patient:
41
Monitoring Safety of Hydroxychloroquine
No lab tests required
HYDROXYCHLOROQUINE --> ophthalmic exam baseline and annually after 5 years
42
Sulfasalazine Safety Monitoring
CBCs and LFTs, creatinine
43
Methotrexate Safety Monitoring
CBCs and LFTs, creatinine
Chest x-ray (baseline) – pulmonary toxicity
44
Leflunomide Safety Monitoring
CBCs and LFTs, creatinine
45
Hydroxychloroquine Efficacy
vs. placebo: decreases # affected joints, pain, QoL assessments
vs. other DMARDs: less effective
Does not decrease radiographic damage
46
Sulfasalazine Efficacy
vs. placebo: Decreases symptoms by half
Vs. other DMARDs: typically less effective
Limited monotherapy evidence
Use if other options not tolerated
47
Methotrexate/Leflunomide Efficacy
“Healing” of bone may occur
48
Rank the relative potencies of the DMARDS
49
Hydroxychloroquine Role in Therapy
Useful for early, mild RA
Best tolerated of the DMARDs
Combined with other
DMARDs -- monotherapy generally rare
50
Role in Therapy Sulfasalazine
Use if other options not tolerated
Most effective the earlier used
Combined with other DMARDs -- monotherapy generally rare
51
Role in Therapy Methotrexate
Highly effective in mod-severe disease
Significantly improves efficacy when combined with biologics
Standard therapy – “backbone”
52
Leflunomide Place in TX
Replacement for MTX if not tolerated
May be added in low doses to MTX
53
Immune Response in RA Involves....
Central to the inflammatory process of RA are monocytes, macrophages and fibroblasts within the synovium, which produce cytokines:
Tumor necrosis factor α (TNF – α)
Interleukins
Overtime, these cause the damage to soft tissue and bone
B and T cells / receptors also a target
54
What are the main classes of biologic DMARD's?
TNF – α inhibitors
Interleukin – 1 or 6 inhibitors
T-Cell Co-stimulation inhibitors
B-Cell depletors
55
What are some common side effects for all biologics?
Nausea
Headache
Diarrhea
Malaise – most common reported one
(Fatigue side effect is short-lived)
56
What are some more serious concerns for biologics?
Injection site reactions
Infection rate increase
Neutropenia
Malignant disease
Antibody development
57
Describe the injection site reactions associated with all biologics? How can it be treated?
SC --> minor redness and itching, swelling, pain.
Lasts 3-5 days each injection
Severity declines over time
IV --> headache and nausea, rash, hives, fever, chills, fatigue
Hypersensitivity
Anaphylaxis uncommon
Often pre-treat: acetaminophen + antihistamine + steroid ~90 min prior
58
Infection risk with biologic DMARD's.When is the risk the highest?
Infection rate increase:
Age and dose related (Under 65, less of a concern)
Incidence in trials was 5-10%/yr (common) or 2-4%/yr (serious) (compared to placebo)
Common infections: sinusitis, pharyngitis, candidiasis, pneumonia, UTIs
Serious infections: TB, mycobacterial, PCP, CMV, zoster, Hep B/C (opurtunitstic/dormant infections)
Risk highest early in therapy
59
How can the risk of infection associated with biologic DMARD's be diminished?
Screen for TB, Hep C, Hep B, HIV prior to therapy
Up to date on vaccinations (esp. influenza / COVID)
Use biologics with a shorter dosing interval in high-risk patients (shorter interval, can stop, wear off faster)
Educate patient on signs of infection (moderate fever/malaise)
Abatacept may be safest option in high-risk patients
Never use two biologics in combination
If infection occurs: consider temporary discontinuation of biologic
60
What to do if someone on a biologic has an infection occur?
If infection occurs: consider temporary discontinuation of biologic
61
Describe the risk of neutropenia associated with biologic DMARD's. WHy is this a concern?
~20% will experience a decrease
Increases severity of infections
Monitoring important
Not a reason to d/c therapy (Small decrease is nothing to worry about)
62
Describe the risk of malignant disease for biologic DMARDS? Management?
RA patients have higher cancer risk, confounding data
Overall: No cancer risk increases except for:
Skin cancer
Lymphomas
Avoid biologics in those active malignancies
Preferentially avoid if previous skin cancer
Use rituximab in those with previous lymphoma
63
Describe antibody development as it pertains to the biologic DMARDS?
Drug Concnetration?
Occurs when?
Predicts?
Highest Risk and MAnagement?
Clearance of drug increased by body’s defenses
Usually occurs within 2-6 months of starting therapy
May also predict development of auto-immune disease
Infliximab likely highest risk (~50%)
Adalimumab and Etanercept lower risk (~12%)
Methotrexate may lower formation
64
What biologic DMARD's develop the most antibody development? Effect of antibody development?
Does not occur with IL-6 inhibitors
T-cell inhibitors and B-cell depletors: possible effect, but less than TNF-inhibitors
TNF-a inhibitors develops the most
Antibody to the biologic – cleared faster – increased injection site rxns, drug effects wanes over time – more and more to sustain its effect
65
What is the MOA of TNF-a inhibitors?
High TNF in RA patients
--> bone erosion
66
What are some examples of TNF-a inhibitors? Differences in efficacy and safety?
Adalimumab
Certolizumab
Etanercept
Golimumab
Infliximab
Efficacy and safety equal between the 5 of them
67
What is ACR50?
ACR50 – what % of pt’s received a 50% reduction in sx
68
Onset of TNF-a inhibitors
Onset – within weeks
69
Efficacy of Tnf-a inhibitors. Effect of efficacy?
ACR50 of ~40%
Combination with MTX is more effective (ACR of 60 to 50)
Slow/stop radiographic progression with bone
70
TNF-a combination with MTX. Benefit?
Infliximab / Golimumab only indicated in combination with MTX
When combined with MTX, reduce risk of antibody development
71
What are some general principles of TNF-a tx?
Infliximab is IV
Subcut is with autoinjectors (can give them themselves)
- Infliximab is every 8 weeks
- Dosing intervals – subcut more frequently
- Biosimilars – some person can get coverage
- Pregnancy – fairly equal in data
- Certolizumab – preferred in pregnancy and breast feeding (even better data)
TNF-a not studie din renal impairment – do not use in this group
72
C.I. of TNF-a Inhibitors
Active severe infection – temporary d/c
Moderate to severe heart failure (increase risk of heart failure)
73
D.I. of TNF-a Inhibitors
Live vaccines – efficacy and infx
Additive immunosuppression with other drugs
74
Adverse Effects of TNF-a Inhibitors (General)
Liver enzyme elevations
Heart Failure (unique concern)
Cutaneous (unique concern (plus rituximab))
Autoimmune disease (unique concern
Seizure risk (unique concern)
75
TNF-a and liver enzyme elevations
Liver enzyme elevations uncommon (1-5%)
Concern if ALT >5x upper limit normal
Requires periodic monitoring (Baseline then regular monitoring)
76
TNF-a and Heart Failure
May cause or worsen existing HF
Use cautiously if needed
Utilize low doses
Evidence is not conclusive
77
TNF-a and Cutaneous
Cutaneous (unique concern (plus rituximab))
Cellulitis
Autoimmune skin diseases (eczema, psoriasis)
Skin malignancy
78
TNF-a and autoimmune Disorders
Lupus
Vasculitis
Sarcoidosis
Psoriasis
79
TNF-a and Seizure Risk
Avoid in patients with seizure disorder
80
Monitoring of TNF-a
TB, HIV, Hep B/C screening
CBCs – neutropenia, or agrunlocytosis
LFTs
Baseline and then every 3-6 months
Signs of infection
Ensure vaccinated
81
Which TNF-a inhibitor to choose?WHat to do if lose function over time?
Track record and time since approval
Frequency of dosing and route
Cost --> consider those with a biosimilar (inf, eta, ada)
Rheumatologist preference
If loss of effect over time check antibodies, consider switching or adding MTX
82
Which TNF-a inhibitor can only be administered via IV?
Infliximab
83
IL Inhibitors MOA
IL-1 and 6 inhibitors antagonize the interleukin receptors reduction in cytokine activity and cartilage damage
84
IL-1 or 6 inhibitors Examples and Place in TX
Anakinra (IL-1)* - poorly efficacious in RA, less potent, less s/e
Tocilizumab (IL-6)
Sarilumab (IL-6)
Can be considered first line along with TNF-a
85
IL-1 or 6 Onset
weeks, but peak at 5-6 months
86
IL-1 and 6 Inhibitor C.I.
Anakinra: None
Tocilizumab: Active infections
Sarilumab: None
87
Anakinra Efficacy Data RA
Less anti-inflammatory than other biologic agents
Likely less effective than other biologics
40% achieve ACR20 vs. 27% placebo
Some radiographic improvement
88
Tocilizumab/Sarilumab IL-1 and 6 Inhibitor Efficay
~40% achieve ACR50 vs. 10% placebo
Similar or potentially more effective than TNF inhibitors (adalimumab)
Some radiographic improvement
89
IL-1 and IL-6 Dosing Adjustments
Anakinra:
CrCL >30ml/min: No adjustment
ESRD: Dose every other day
Tocilizumab and Sarilumab
CrCL >30ml/min: No adjustment
IL-1 and 6 inhibitors are only ones that have robust renal impairment data
90
Anakinra A/E
Injection-site reactions and infections
Overall serious adverse effects similar to placebo rate
Headache and Nauseau
91
A/e of Tocilizumab/Sarilumab
GI perforation (unique + rituximab)
Rare
Caution if at risk of GI issues
Ulcer and sepsis risk
Dyslipidemia (unique): ↑ TC / TG and ↓HDL
Antibody development not linked to decreased effect (unique)
Hypertension – small increase
Other concerns similar to TNF inhibitors (common ADRs, LFTs, infections,
92
What other drug is often started alongside Tocilizumab / Sarilumab?
Other factors for metabolic – often will see people on statins here to deal – use target high doses of statin
93
D.I. of the IL-1 and 6 Inhibitors
Drug Interactions
All:
Decreased IL1 or 6 activity = Increased CYP activity
Additive immunosuppression
Live vaccines
Tocilizumab
Simvastatin increased 4-10x
Choose any other statin here
94
Monitoring of IL-1 and 6 Inhibitors
Anakinra: Baseline CBC, LFTs, creatinine; then every 3-6 months
Tocilizumab / Sarilumab:
Baseline CBC, LFTs, creatinine; repeating in 4-8 weeks after starting, then every 3-6 months
Lipid panel
Blood pressure
Latent / active TB, Hep B/C screening
95
T-cell Co-Stimulation Inhibitor MOA and Use
Inhibits T-cell activation
Used if inadequate response to DMARDs or TNF inhibitors
Monotherapy or combination with traditional DMARDs (MTX)
Includes: Abatacept
Less data than other biologics
96
Efficacy of T-cell Co-Stimulation Inhibitor
41% achieved ACR50 vs. 20% placebo at one year
Dosage and administration
97
Adverse Effects of T Cell Co-Stimulation Inhibitor
Similar to TNF inhibitor – infections (likely lower risk), neutropenia, common ADRs
COPD exacerbations (unique)
No impact on liver function (unique)
Hypertension
Blood glucose increased
Unknown if antibodies impact efficacy or safety
98
Monitoring of T-Cell Co-Stimulation Inhibitor
Signs and symptoms of infection
TB and hepatitis screening
CBCs, creatinine
Blood pressure
Blood glucose – not mandatory – if pre-diabetic or risk factors
99
B-cell depletor MOA, Example
B-cells central to immune memory and the production of auto-antibodies
B-cell depletors bind to B-cells to cause lysis
Includes: Rituximab
100
B-cell Depletor Use, Onset, Efficacy Data
Only studied in combination with MTX AND failure on a TNF inhibitor
Onset – May be delayed up to 6 months
Efficacy data:
ACR50 of 43% vs. 13% placebo
Does not work well in RF-negative patients
No halt of radiographic progression
101
B-cell Depletor Times of Administration
2 dose course: 1g IV infusion given two weeks apart
Must pretreat with methylprednisolone, acetaminophen and diphenhydramine
Re-treat when needed (~6 months) – some only need to retreat every 1-2 years
Some require two courses for efficacy
Withhold hypertension medication morning of infusion
Pre-tx protocol – methylprednisone, diphenhydramine, and acetaminophen – reduce risk of anaphylactic rxn
102
A/E Of B-cell Depletor
Infusion reactions tend to be more rapid, but mild and brief
Serious infection rate is non-existent initially; then increases on repeat courses
Hypertension
GI perforation
Blood glucose increase
Mucocutaneous reactions (SJS, TEN) – reported, more common than other biologics
Antibody formation likely leads to increased infusion reactions and decreased efficacy
103
B-cell Depletor Monitoring
Baseline CBC, LFTs, creatinine
TB, Hepatitis B/C screening
104
What drives us to choose a certain biologic? (REMEMEBER)
105
Biologic DMARD's Place in TX
Biologics considered once other options have been tried
Exception: Initial severe case of RA
TNF – α inhibitors
Initial biologic of choice for most
Interleukin – 1 or 6 inhibitors
Anakinra: for those risk averse or who cannot tolerate other DMARDs
Tocilizumab / Sarilumab: for moderate to severe RA, often in combination with MTX
Both: if antibodies to others biologic DMARDs have formed
T-Cell Co-stimulation inhibitors
When traditional DMARDs or TNF inhibitors have failed
B-Cell depletors
Combo with MTX when others have failed
Use if history of lymphoma
106
Janus-Kinase Inhibitors MOA, Use, Examples, Role in TX
Janus Kinase are a group of enzymes responsible for enabling interleukin signalling
Indicated preferably in combination with MTX
May be used as monotherapy if MTX intolerance
Other combinations not recommended
Includes: Tofacitinib, Baricitinib, Upadacitinib
Place in therapy: Last line option
107
Efficacy of Janus Kinase Inhibitor
Combined with MTX: ACR50 46% vs. 20% placebo
Monotherapy: ACR50 of 38%
108
A/E Janus Kinase Inhibitor
Similar to TNF inhibitors and other biologics, including:
HTN
Infections / cytopenia
LFTs / hepatotoxicity
Bradycardia
GI perforation
Drop out rates of ~10%
No concern about antibody development
109
C.I. Janus Kinase Inhibitor
Use during severe infections
110
Warnings Janus Kinase Inhibitor
*New data* - CV risk (MI, clots) - NNH 113/5yrs
*New data* - Malignancy (lung cancer, lymphoma)
GI perforations
Bradycardia
Dyslipidemia
111
D.I. Janus Kinase Inhibitors
Tofactinib / upadacitinib are major 3A4 substrates; baricitinib is a minor 3A4 substrate
Live vaccines
Additive immunosuppression
112
Janus Kinase Inhibitor MOnitoring
Latent TB testing
Lipid profile
CBCs every 3-6m months
LFTs
113
Janus Kinase Inhibitor Preganancy
Pregnancy / lactation – limited data, use better studied alternatives
114
Corticosteroids in RA Use, MOA
Important tool for RA treatment
Majority of patients will use in course of disease
Likely has DMARD properties and decreases early progression of RA
Significant controversy on optimal utilization
115
Corticosteroids Efficacy. Main Benefit?
Reduces joint tenderness more than placebo and NSAIDs
Reduces pain more than NSAIDs
Improved QoL measures
Small radiographic progression decrease
Main benefit: subjective symptomatic improvement
116
Tx Modalities of Corticosteroids in RA
1) Short-term use
Doses of 10-15mg prednisone equivalent per day (low dose)
Taper and d/c as symptoms improve
Limited safety issues if dose / duration kept low
2) Chronic Use
Doses of 5-10mg prednisone equivalent per day indefinitely
Long-term steroid safety issues become apparent
Increases need for monitoring and adjunctive treatments
3) Pulse Therapy
Administer high doses for a few days
Methylprednisolone 1000mg IV for 3 consecutive days once monthly for 6-8 months
Safety issues: cardiovascular collapse, hypokalemia, myocardial infarction, severe infection
Considered a last resort option in RA
117
Corticosteroids Onset
Within days
118
Corticosteroids S/e
Cataracts
Dyslipidemia
Hyperglycemia
Osteoporosis
Weight gain
119
Intra-articular Injections of Corticosteroids
Safe and effective when done by experienced MD
Effects dramatic, but temporary
Same joint should not be done more than once per 3 months
Considered “palliative”
Rest joint for 3 days after injection
120
Issues with Intra-articular injections of corticosteroids
tendon rupture
acute synovitis
localized skin hypopigmentation
septic arthritis
121
Guideline Approach for Corticosteroid USage
Consider for flares or as “bridging”
Aim for a max dose of 10mg/d
Never use as monotherapy
Find minimum dose/duration
Consider avoiding in those more at risk of steroid side effects
122
NSAID's Use in RA
Provide high dose NSAIDs at initial diagnosis
Use for at least 2 weeks for maximum benefit
Cautiously combined with other treatments (e.g. corticosteroid)
Consider providing GI protection
Should not need to use chronically
123
Do NSAID's help with the underlying dx process?
Do not do anything to effect underlying disease process
GI Risk and Bleed heightned with steroids and NSAID
124
Other analgesics used in RA
Acetaminophen sometimes added (2g/day)
Avoid opioids
Limited evidence in RA
Proper DMARD use and non-pharm is greater benefit
125
Combination TX for RA
NSAIDs + Glucocorticoids can be added to any regimen (extra caution with NSAID and Steroids together)
MTX can be added to all biologics
LEF + biologics similar to MTX + biologics
tDMARD double therapy - any two of MTX, SSZ, HCQ or LEF
tDMARD triple therapy - MTX + SSZ + HCQ
ACR50 of single, double or triple combo tDMARDs: 29%, 40% and 55%
Biologic + two tDMARDs – unclear benefit/harm; “reasonable” in guidelines
Recommend AGAINST multiple biologics
ACR50 of MTX vs. MTX + biologic: 20% vs. 58%
126
Flare Management for RA
Intraarticular glucocorticoid if few joints
Initiate / increase glucocorticoid
Consider increasing DMARD doses
Add new DMARDs if frequent flares
127
First-line Initial therapy approach for low disease activity?
Conditional recommendation, in order of preference for initial therapy: HCQ > SSZ > MTX > LEF
Monotherapy preferred
128
First-line Initial therapy approach for moderate-to-high disease activity?
Methotrexate strongly recommended over HCQ or SSZ
Methotrexate conditionally recommended over leflunomide
Methotrexate monotherapy recommended over double or triple traditional DMARDs therapy
Methotrexate monotherapy conditionally recommended over combo with biologics
129
When monotx fails to achieve goal of therapy?
Preferentially add a biologic DMARD instead of SSZ/HCQ
130
When should RA tx be escalated?
Failure to achieve remission or acceptable disease activity after 3-6 months at optimal doses
Inability to taper steroids
Recurrent flares (2 or more flares per year; escalate tx if happening; 1 flare per year still a strong consideration)
Disease progression on Xray
131
Pregnancy: Agents to Avoid
Must discontinue unsafe medications
MTX – male and female - stop for 3 months prior to conception
Leflunomide – male and female – take cholestyramine, measure levels until <0.02mg/ml, then wait an additional 3 months
132
Goal of TX in Pregnancy
Achieve remission on safe options:
HCQ and SSZ good options
All biologic agents, except rituximab, have favourable safety profiles
Certolizumab has the most robust data; compatible with all trimesters
133
Peri-Preganancy RA Options
Corticosteroids may be used sparingly
Ensure folic acid 5mg/d if previous MTX use
Cautious use of NSAIDs – C.I. in third trimester, strong precaution in 1st trimester, 2nd semester is safer
134
Post-partum RA Tx
Flares common
Return to pre-pregnancy regimen/doses if compatible with breastfeeding
135
Lactation RA Tx
NSAID use (ibuprofen preferred) acceptable
Low dose prednisone (<20mg/d) compatible
HCQ and SSZ safe to continue
TNF-inhibitors, IL-6 inhibitors safe
Continue to avoid MTX and LEF
Other agents: limited data or not studied
