Rheumatoid Arthritis Treatment Flashcards
What is the goal of RA Treatment?
Low disease activity or remission
What is DMARDs and what is included?
Disease modifying anti rheumatic drugs
1. Nonbiologic
2. Biologic
NSAIDs have what main effect in RA treatment?
Anti-Inflammatory
HPA Axis Steps
Hypothalamus: Corticotropin releasing hormone –> Pituitary: Corticotropin ACTH –> Adrenals: Cortisol –> neg feedback on Pituitary
What are the indications of Corticosteroids?
- Extaarticular disease
- Vasculitis
- Active RA during pregnancy or breastfeeding
What are the AEs of Corticosteroids?
- 2-4x increased GI risks when given with NSAIDs
- Moon face
What can be accelerated with corticosteroids?
Atherosclerosis or Osteoporosis
How can you prevent osteoporosis when taking corticosteroids?
- Calcium
- Vitamin D
- Weight baring exercise
- Bisphosphonate if moderate/high fracture risk
When is pulse dose IV methylprednisolone used?
Lupus
When is IM depot methylprednisolone used?
Immediate relief of pain
What are the Nonbiologic DMARDs csDMARDs?
- Methotrexate
- Sulfasalazine
- Leflunomide
- Hydroxychloroquine
- Minocycline
- Cyclosporine
- Azathioprine
- Gold
- D-Penicillamine
What is the primary nonbiological drug for RA?
Methotrexate
Methotrexate absorption decreases with what?
Increased doses and food
What is the onset of effect for Methotrexate?
Onset 3-6 weeks, max effect 3-6 months
What is the hepatic concern with Methotrexate?
Fibrosis and Cirrhosis
What is the pulmonary concern with Methotrexate?
Acute hypersensitivity pneumonitis vs. toxic drug reaction
Dyspnea, drug cough, and fever
What are the toxicities of Methotrexate?
- Fetal abnormalities/abortifacient
- Oligospermia
How do you decrease toxicity of Methotrexate?
Take with Folic Acid 1 mg/day
What are the drugs that can cause decreased renal clearance and increased risk of toxicity of Methotrexate?
- Probenecid
- Salicylate
- NSAIDs
- Diuretics
What are the drugs that displace Methotrexate from binding sites?
- Salicylate
- Sulfonamides
- Phenytoin
What are the CIs of Methotrexate?
- Acute or chronic liver disease
- Excessive alcohol consumption
- Pregnanc
What is precaution of Methotrexate?
Obesity, diabetes aka Fatty Liver, which the risk of fatty liver can be increased with Methotrexate
What is the dosing frequency of Methotrexate?
EVERY WEEK
PUT DAY of week on the Rx Label
What are the monitoring concerns with Methotrexate?
- CBC
- Cr
- Liver Enzymes
Q2-4 wks every 3 months, then q8-12 weeks for 3-6 months, and then q12 weeks after 6 months
What is the main takeaway of Methotrexate in RA?
Initial drug of choice, anchor for most combinations
What is the efficacy monitoring of Sulfasalazine?
- Improvement detectable at 4-8 weeks
- Failure identifiable within 3 months
What is the CI of Sulfasalazine?
Hypersensitivity to salicylate or sulfonamide
What is the monitoring for Sulfasalazine?
- Baseline G6PD
- CBC and LFTs within 1 month
What is the main toxicity of Sulfasalazine?
GI Effects 19%
What is the concern of Sulfasalazine during pregnancy?
Safe during pregnancy, but NOT safe AT TERM because it can cause Kernicterus: jaundice in the newborn
What are the PK parameters of Leflunomide?
Prodrug for Teriflunomide and still detectable 2 years later
What is the main toxicity of Leflunomide?
Increased LFTs, Severe Liver Injury
Stop is ALY 3x ULN
What are the CIs of Leflunomide?
- Teratogenicity
- Prior to pregnancy, drug is eliminated with cholestyramine until plasma concentration <0.02 ng/L
What is the monitoring of Leflunomide?
- Baseline Hep B and C
- Same as MTX and SAS
How long does it take to determine efficacy of Hydrochloroquine?
6 months to determine failure
In mild RA, how is Hydrochloroquine utilized?
Monotherapy
What is the elimination half life of Hydrochloroquine?
40 days
What is the main side effect of hydrochloroquine, and what is a side effect that Dr. Resman-Targoff was surprised by?
- Retinal Damage
- Skin Hyperpigmentation (dr. resman)
What are the counseling points of Hydroxychloroquine?
- Considered safe in pregnancy
- Take with food or milk
What are the monitoring parameters of Hydroxychloroquine?
- CBC
- LFTs
- Creatinine
What is Minocycline?
- Not currently in ACR RA treatment guidelines
- Previously used for Mild RA off label
What is the plasma half life of Cyclosporine?
1-45 hrs
What is the efficacy of Cyclosporine?
Seen at 2-12 weeks
Peaks at 6 months
What are the toxicities of Cyclosporine?
- Nephrotoxicity
- Hypertension
- Gingival Hyperplasia
- Hyperkalemia
- Hypomagnesemia
- Hyperuricemia
- GI
- Neuropathies
- Hirsutism
What are the monitoring parameters of Cyclosporine?
- Cr
- BP
- K
- Uric Acid
There is a high risk of toxicity for Azathioprine is what?
Low or Absent TPMT
What is the concern in pregnancy for Azathioprine?
Considered safe in pregnancy but use CI by manufacturer?
What is the efficacy of Azathioprine?
Onset 6-12 weeks
Peak 6 months
What are the Targeted Synthetic DMARDs/Oral Janus Kinase JAK Inhibitors?
- Xeljanz
- Olumiant
- Rinvoq
How to spell Tofacitinib brand name?
X E L J A N Z
How to spell Baricitinib brand name?
O L U M I A N T
How to spell Upadacitinib brand name?
R I N V O Q
What can you NOT combine JAK Inhibitors with?
- Azathioprine
- Cyclosporine
- Tacrolimus
- Biologics
- Other JAK Inhibitors
What is the toxicity of JAK Inhibitors?
- Thrombosis
- Zoster
- GI Perforation
- Increased LDL Cholesterol
- Increased LFTs
What is a risk of JAK Inhibitors?
Risk of Major CV Events and malignancy
What should monitor for with JAK Inhibitors?
- CLOTS
- CBC
- Lipid Panel
- Infections
Xeljanz dosing is what?
PO
Olumiant dosing and caution is what?
PO
Not used for GFR <60
Rinvoq dosing and caution is what?
PO
AVOID if severe hepatic impairment
What are the Anti-TNF Monoclonal Antibodies?
- Infliximab
- Adalimumab
- Golimumab
- Certolizumab Pegol
- Entanercept
- Rituximab
- Abatacept
What does (I)I mean?
Immune target
What does xi mean?
Chimeric
What does (m)u mean?
Fully human
What does zu mean?
Humanized
What should you avoid when taking TNFa Inhibitors?
Avoid foods with listeria risk
What happens to the fetus when mother is taking TNFa Inhibitors?
Immunosuppression after birth
What is the MOA of Etanercept and its dosing?
Soluble TNF receptor, binds TNFa, blockers interaction
SUB Q
What is the main drug warning of Entanercept?
CNS Demyelinating disorders
What is the MOA of Infliximab and its dosing?
Chimeric, binds to TBFa
IV INFUSION
What are the toxicities of Infliximab?
- TB Reactivation
- Acute infusion reaction
- Hypesensitivity
- Increased infection risk
What is the MOA of Adalimumab and its dosing?
HUMAN IgG1, binds TNFa
SUB Q, Without or without MTX
What is the MOA of Golimumab and its dosing?
HUMAN IgG1, binds TNFa
SUB Q or IV WITH MTX in RA
What is the MOA of Certolizumab Pegol and its dosing?
Peglayted Fab Fragment
SUB Q, alone or with nonbiologic DMARD in RA
What is the MOA of Rituximab?
CHIMERIC, directed against B cell surface antigen CD20, depletes B Cells
When do you use Rituximab in RA?
- Active RA
- Inadequate response or intolerance to TNF inhibitors
Can you use Rituximab in pregnancy?
NO, not recommended
What is the dosing of Rituximab?
- With MTX
- IV Infusion day 1 and 15
- Q 24 weeks
What is the MOA of Abatacept?
Selective Costimulation Modulator
What are the toxicities of Abatacept?
COPD Exacerbations
What is the dosing of Abatacept?
IV Infusion or SUB Q
Avoid silicone syringes
What are the Il-6 Antagonists?
- Tocilizumab
- Sarilumab
- Anakinra
What is the MOA of Tocilizumab?
HUMANIZED IL-6 Receptor inhibiting monoclonal antibody
What is the toxicity of Tocilizumab?
- Gastrointestinal perforation
Increased liver enzymes and lipids, decreased neutrophils and platelets
Can you use Tocilizumab in pregnancy?
NO
What is the dosing of Tocilizumab?
IV Infusion or SUB Q
What is the MOA of Sarilumab?
FULLY HUMAN IL-6 receptor inhibiting monoclonal antibody
What are the toxicities of Sarilumab?
- GI Perforation
Increased liver enzymes and lipids
What is the dosing for Sarilumab?
SUB Q
What is the MOA of Anakinra?
RECOMBINANT IL-6 receptor antagonist
What is the dosing of Anakinra?
SUB Q DAILY
Is Anakinra recommended in pregnancy?
NO
What is Comorbidity?
2 simultaneous diseases that occur together more often than by chance
What is Multimorbidity?
2 simultaneous disease that occur together randomly
What should be in lab monitoring of RA?
- ESR
- CRP
- Hemoglobin/Hamtocrit
- Platelets
- X-Rays
Do you use RF in monitoring of RA?
NO, only used to establish diagnosis
What are the RA Treatment Strategies?
- Combo therapy
- A+B+C+D
- Methotrexate Anchor
Why do you want to give Chimeric monoclonal antibodies with Methotrexate?
To decrease formation
Can Biologics and JAK Inhibitors be combined?
NO
Which drug needs an elimination procedure prior to pregnancy and what is it?
Leflunomide, eliminate with Cholestryramine
What is the initial treatment guideline?
- DMARD naive, low disease activity = HCQ>MTX>LEF
- DMARD naive, mod/high disease activity = MTX mono>HCQ mono, SAS, bDMARD, tsDMARD, or combo
- csDMARD without glucocorticoid preferred
What is methotrexate admin guideline?
Initial oral MTX preferred over SUB Q
What is the treatment modification guideline?
- Max tolerated MTX dose, adding bDMARD or tsDMARD preferred over cs DMARD triple therapy
- Adding/switching DMARDs preferred over continuing/adding glucocorticoid to stay at target
What is the tapering of DMARD guideline?
- Gradually DC Drugs
- If on triple csDMARDs, gradually DC SAS>HCQ
- Gradually DC MTX>stopping bDMARD or tsDMARD
How long should RA treatment be at target prior to tapering?
At target >6 months before tapering
When should you screen TB?
Before biologic or JAK inhibitor
Which drugs have the highest reactivation of tuberculosis?
TNFa Inhibitors Infliximab or Adalimumab
What is the screening for TB?
- Screen with PPD or IGRA, if positive get CXR
- If CXR positive, get sputum for AFB
- If AFB positive, treat for TB >3 months before starting biologic/JAK
- If AFB or CXR neg, treat for latent Tb 1 month before biologic/JAK
Immunosuppressed patients may have diminished response to vaccines and increased risk for infections. Vaccine may trigger autoimmune diseases and therefore,
Should be administered before starting
For patients older than 50 yrs what vaccine should you consider?
Shingrix, especially before JAK inhibitors