Overview
Goals of therapy
Maintain normal activities of daily living by reducing inflammation to lowest levels possible, prevent structural damage or progression of disease, achieve remission or low disease activity
Which of the non-biological are conventional? Targeted?
Conventional: methotrexate, hydroxycchloroquine, leflunomide, sulfasalazine
Targeted: tofacitinib, upadacitinib, baricitinib
What is the BBW of Xeljanz?
serious infections, lymphoma and other malignancies, thrombosis, increased all cause mortality, TB
What is the BBW for all Anti-TNF DMARDs?
Severe infections, lymphomas or other malignancies, TB
Can we use combo therapy? If so, which classes can we combine?
Yes, recommended to use csDMARDs in combo, csDMARDs are recommended in combo with bDMARDs or tsDMARDs
Biological DMARDs should NOT be used in combo
Non pharm therapy
What is first line for RA? Dose range?
Methotrexate 7.5-20 mg PO, IM, SQ once weekly
Hydroxychloroquine (Plaquenil) onset, AE, warnings, monitoring?
Onset is several weeks
AE: retinopathy, N/V, diarrhea, rash, pigmentation changes, increased LFTs
Warnings: cardiomyopathy, bone marrow suppression
Monitoring: CBC, LFTs, sCr, eye exams, labs baseline and periodically
What are some common warnings and precautions for Anti-TNF DMARDs?
auto immune disorders-drug induced lupus like syndrome, CV/cerebrovascular rxns, hematologic disorders, hepatic rxns, hepatitis B reactivation
What are the 3 main steps for treatment approach?
Methotrexate, combo of synthetic DMARDs or add biologic, change to alternative bDMARD or tsDMARD
What % reduction in disease activity are we aiming for in what period of time?
> or = 50% reduction within 3 months and low disease activity within 6 months
Methotrexate AE, CI, monitoring? What deficiency is it known to cause?
AE: thrombocytopenia, leukopenia, N/V, diarrhea, liver damage, alopecia, renal damage, folic acid deficiency
CI: pregnancy, alcoholism, liver disease, preexisting blood dyscrasias
Monitor: CBC with diff, LFTs, sCr, Hep B and C serology, labs baseline 2-4 weeks for 3 months and continue to increase interval
Folic acid deficiency
Tofacitinib (Xeljanz) onset, AE, warnings, monitoring?
onset about 2 weeks
AE: infection, diarrhea, nausea, HA
warnings: bone marrow suppression, decreased HR, GI perforations, hepatotoxic
Monitoring: CBC, LFTs, sCr, lipids
What are the Anti-TNF DMARDs?
Infliximab (Remicade), Adalimumab (Humira), Etanercept (Enbrel), Golimumab (Simponi), Caertolizumab Pegol (Cimzia)
(Non-TNF) Anakinra (Kineret) main AEs, warnings, monitoring?
HA, vomiting, infection, arthralgia, nausea, diarrhea
Warnings: infections, malignancy, neutropenia, renal impairment
Monitoring: CBC baseline every month x3 months, sCr
What 2 classes are used for symptomatic treatment? Place in therapy?
NSAIDs: use as adjunct therapy at lowest effective dose for shortest duration possible, generally not used as monotherapy
Steroids: use as adjunct therapy, short and long term uses at lowest effective dose, may be used as bridge therapy when starting disease modifying agents
What is the typical alternative to methotrexate? AE? CI? Monitoring?
Leflunomide (Arava)
AE: HA, alopecia, rash, diarrhea, nausea, increased LFTs, URTI
CI: severe hepatic impairment, pregnancy
monitoring: pregnancy test prior to initiation, CBC, LFTs, labs monthly for first 6 months, then increase interval
Upadacitinib (Rinvoq) MOA, AEs, monitoring, BBW?
JAK inhibitor
AE: URTI, neutropenia, nausea, thrombosis, increased lipids
Monitoring: CBCs, LFTs, lipids
BBWs: serious infections, malignancies, thrombosis
(Non-TNF) Rituximab (Rituxan) main AEs, warnings, monitoring?
Warnings: bowel obstruction, CV effects, cytopenias
Monitoring: CBC and platelets prior each infusion, HBV screening
(Non-TNF) Abatacept (Orencia) main AEs, warnings, monitoring?
HA, nausea, infection, URTI, HTN
Warnings: infections, malignancy
TB and HBV screening
What 3 classes of drugs are used for chronic treatment? If patients enter remission, can we discontinue all DMARDS?
Non-biological DMARDs, Anti-TNF DMARDs, Non-TNF DMARDs
Not recommended, can taper down by removing one medication at a time but risk of flare needs to be discussed with patient
Sulfasalazine (Azulfidine) duration to onset, AE, CI, montoring?
Onset >4 weeks
AE: HA, rash, nausea, dyspepsia, anorexia
CI: hypersensitivity to sulfa or salicylate preparations, GI or GU obstruction
Monitoring: CBC, LFTs, renal function, labs every other week for the first 3 months, then increase interval
Baricitinib MOA, AE, monitoring, BBW?
JAK inhibitor
AE: URTI, nausea, thrombosis, increased LFTs and lipids
Monitoring: CBCs, LFTs, lipids
BBW: serious infections, malignancies, thrombosis
(Non-TNF) Tocilizumab (Acetemra) main AEs, warnings, monitor?
Increase in cholesterol, increase in LFTs, HTN, HA, diarrhea
Warnings: perforation, hepatic effects, hyperlipidemia
Monitor: TB screening, neutrophils and platelets, LFTs, lipid panel
(Non-TNF) Sarilumab (Kevzara) main AE, warnings, monitoring?
Increased LFTs, neutropenia
Warnings: GI perforation, hepatic effects, hematologic effects, hyperlipidemia
Monitor: Neutrophils, platelets, LFTs, TB screening, lipid panel