Derm FINAL Exam: Yamaki DMARD and RA (bolded+underlined)

Epidemiology of Rheumatoid Arthritis

• Onset is 3rd to 4th decades of life, and prevalence increases with advancing age (Usually manifests ~______).

50 years

Etiology of RA

• Immune cells, pro-inflammatory cytokines, and signaling pathway:

  • T cells (______ mediated)

  • B cells (______ mediated)

  • ______, ______ and ______

  • ______

cell, humoral, TNF, IL-1, IL-6, JAK

Rheumatoid Arthritis (RA)

• Inflammatory polyarthritis, especially the ______ of the hands and feet.

• Untreated chronic inflammation → joint erosions and joint destruction.

• Need to treat to prevent ______

• RA is characterized by:

  • autoantibody production [______, ______]; highly specific for RA

smaller joints, progression on destruction, RF, ACPA

Clinical S/Sxs

• Slow but progressive

• Stiffness is ______

• Can decrease stiffness in the ______ with ______

worst in AM, AM, activity

S/Sxs

• Untreated RA can go beyond joints and ultimately affect ______

organs

Diagnosis of RA

• Score of ______ indicates RA

• High Specificity for RA diagnosis: ______ and ______

6 or greater, RF, ACPA

General Principles in the Treatment of RA

• ______ treatment for ALL patients diagnosed with RA. (More aggressive than previous approaches decades ago)

• Baseline testing before starting ______:

  • ______ with differentials (cell counts)

  • ______ (liver function tests)

  • ______ (renal function)

• Selection of ______ based on:

  • severity of RA & stage of RA (DMARDs naïve or experienced)

  • patient’s preference

  • insurance coverage

  • presence of adverse prognostic findings (______, other factors)

• Anti-inflammatory (NSAIDS) or glucocorticoid therapy for ______ only (gap of onset)

• ______: Achieve and maintain tight control of disease activity, defined as remission or a state of low disease activity

• Treatment failure defined as lack of ______, following ______ of ______ at optimal dosing

DMARD, DMARD, CBC, LFTs, BUN/SCr, DMARDs, comorbid conditions, bridging therapy, Treat to Target, remission/low disease activity, 3-6 months, DMARDs

DMARD naïve - Low vs High RA Activity

• Level of RA activity will guide how to start treatment for patients ______ to patient specific factors

in addition

DMARDs

• Non-Biologics

  • ______ (______)

  • Hydroxychloroquine (Plaquienil)

  • Sulfasalazine (Azufidine)

  • Leflunomide (Arava)

  • ok to combine with each other, up to ______ therapy (non-b + non-b and non-b + biologic)

• Biologics

  • -mab and -cept

  • Tofacitinib & Baricitinib (JAK/STAT kinase inhibitors) → technically not a biologic

  • do not combine biologic DMARDs with each other

Methotrexate, Trexal, triple

Methotrexate (MTX)

• Anti-inflammatory and immunosuppressive action (______)

  • Given ______ PO or SQ, start with PO

• SEs

  • LFT ______ (monitor for liver dysfunction)

  • ______ of blood counts (monitor CBC)

  • Decreases ______ (take supplemental ______ 1mg PO daily)

  • Leucovorin (folinic acid) can be used if folic acid does not help

    • Potential to decrease MTX efficacy with ______ (avoid ______ administration PO/IV)

• Contraindicated

  • Liver disease (severe)

  • ______

• Precautions

  • ______ (AKI or CKD)

  • ______

1st Line DOC for moderate/high, weekly, increases, suppression, folic acid, folic acid, Leucovorin, same day, Pregnancy, renal elimination, liver dysfunction

Hydroxychloroquine (HCQ)

• Moderately effective ______

• ______

• Side effects (well tolerated in general)

  • Rare (but serious): ______ (retinopathy) with long-term use with doses greater than 5 mg/kg

  • Patients should have a complete ______ done at baseline and every 5 years thereafter

alone for mild RA, Safe in pregnancy, retinal toxicity, eye exam

Sulfasalazine (SSZ)

• ______ (______)

• ______

• SEs

  • GI upset (nausea and vomiting) may limit use, rash development

  • Serious:

    • Hepatitis- monitor LFTs

    • Leukopenia- monitor CBC

    • Agranulocytosis

onset, takes a long time, Safe in Pregnancy

Leflunomide (LEF)

• SEs

  • Diarrhea is most commonly the limiting effect in treatment

  • ______

  • ______

  • Rash

  • Reversible alopecia

  • Rare but serious - ______ and ______

• C/I

  • ______ and carcinogenic in animal studies (______)

Liver toxicity, myelosuppression, interstitial lung disease, peripheral neuropathy, teratogenic, do not use in pregnancy

KNOW IMAGE

Do NOT combine ______ with each other

biologic DMARDs

TNF Inhibitors (EIACG) → Anti-TNF Biologics

• TNF inhibitors: Etanercept, Infliximab, Adalimumab, Certolizumab, Golimumab

• Common SEs (boxed warning):

  • ______: URTI, pneumonia, UTI, skin and soft tissue infection

  • ______: ______ (reactivation of latent disease), invasive fungal infections, reactivation of hepatitis B. ______ BEFORE STARTING!

  • ______: lymphoma, nonmelanoma skin cancer

• Warnings, precautions:

  • Not recommended in patients with ______, transient ______, and ______ dyscrasias

Infection, Opportunistic Infection, TB, must treat TB completely, Cancer, CHF, neutropenia, blood

T-Cell Co-Stimulatory Blockade

• Abatacept Adverse Effects

  • Increased risk of ______ (mild to severe)

    • Pneumonia (esp. in patients with ______), opportunistic infections (less risk than TNFi’s)

    • TB cases have been ______, but screening is still recommended. (Can start if being treated currently for ______, preferred over ______)

infections, COPD, few, TB, TNFi

Interleukin-6 Inhibition

• Tocilizumab (Actemra®) SEs

  • Increase risk of ______. (Can start if being treated currently for ______)

  • Increased risk of ______

infection and serious infection, TB, GI perforation

B-Cell Depletion

• Rituximab Adverse Effects

  • Infections: ______ (______)

reactivation of viral infections, HepB

JAK Inhibitors

• Precautions: ______

• Warnings

  • ______, serious infections (______, bacteria, invasive fungal, viral and opportunistic infections), lymphoma, ______, viral reactivation EBV & HSV.

  • ______

Infections, Thrombosis, TB, malignancies, Do not use in pregnancy

Comparison of Biologics (and JAK/STATi) + ADRs

• Infliximab, adalimumab, etanercept, etc. (TNF Inhibitors) → ______, ______ ______

• Tocilizumab (IL-6 inhibitor) → ______

• Tofacitinib / Baricitinib (JAK inhibitors) → ______

cancer, HF, exacerbation, GI perforation, Boxed Warning of VTE/PE

Treatment Goals

• ______ approach

• Evaluate ______ for treatment success

Treatment Approach

• Combo Traditional DMARDs → DMARD non-biologic

• Preferred ______ over combo traditional DMARDs

  • TNF Inhibitors +/- MTX

  • Non-TNF Biologic +/- MTX

• At this point >6 months

Treat to target, every 3 months, Now

• Still Lack of Response/Improvement, Not at Target

  • ______ (e.g., ______) or ______ added to ______ (1st line)

• Still Lack of Response/Improvement, Not at target

  • Change to a different class of ______ e.g, ______ → ______ or ______

Add biologic DMARD, TNFi, JAK/STAT-i, MTX, Biologic, TNFi, non-TNFi, JAK/STAT-i

RA Remission/Low Activity

• Approach if only on MTX → ______

• If on MTX + biologic or JAKi, can start to gradually discontinue ______

Decrease dose (taper), MTX