Derm Exam 2: Yamaki RA

Epidemiology of RA

• 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:

  • ______ (______ mediated)

  • ______ (______ mediated)

  • ______, ______, and ______

  • ______

T cells, cell, B cells, 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 ______

• RA is characterized by:

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

  • synovial ______ and hyperplasia (pannus);

  • cartilage and ______ (deformity); and

  • extra-articular involvement: CV, pulmonary, skeletal, ocular, and skin involvement

  • Inflamed and pain in joint, bone deformity, etc.

smaller joints, prevent progression of destruction, RF, ACPA, inflammation, bone destruction

Clinical S/Sxs

• Slow but progressive

• Stiffness is ______

• Can decrease stiffness in the AM ______

worst in the morning, with activity

Common Joints of Involvement

• Most common joint involvement: ______ joints affected, no ______

  • ______ (90%)

    • ______ joint (PIP)

    • ______ joint (MCP)

  • ______ (90%)

    • metatarsophalengeal joint (MTP)

1st or 2nd, distal, hands, proximal interphalangeal, metacarpophalangeal, toes and feet

Signs and Symptoms

• Untreated RA can go beyond joints and ultimately ______

affect organs

Diagnosis of RA

• Score of ______ indicates RA

• High Specificity for RA diagnosis

  • ______

  • ______ (highly specific for RA)

6 or higher, RF, ACPA

General Principles in the Treatment of RA

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

• Baseline testing before starting DMARDs:

  • ______ with differentials (cell counts)

  • ______

  • ______ (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)

DMARD, all pts, CBC, LFTs, BUN/SCr, DMARDs, comorbid conditions

General Principles in the Treatment of RA

• Anti-inflammatory (______) or ______ therapy for ______ therapy ONLY

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

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

NSAIDs, glucocorticoid, bridging, treat to target, remission, low disease activity, lack of remission, low disease activity, 3-6 months

Functional Status Instrument Tools

• ______ is worse

higher number

Non-Pharm Therapy

• Relate to Help Inflammation

  • ______

  • ______

  • ______ (______ = pro-inflammatory)

  • ______ reduction

  • ______

• Counseling

• Physical Therapy

• Surgery (last resort) - aims to relieve pain, correct deformities, improve joint function  → enhancing the quality of life

Exercise, massage, smoking cessation, smoking, stress, diet

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

  • ______ (______)

  • HCQ (Plaquienil)

  • Sulfasalazine (Azufidine)

  • Leflunomide (Arava)

  • ______ combine with each other, ______ (non-b + non-b and non-b + biologic)

• Biologics

  • -mab and -cept

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

  • ______ combine biologic DMARDS with each other

Methotrexate, Trexal, okay to, up to triple therapy, Do not

Methotrexate (MTX)

• Anti-inflammatory and immunosuppressive action (1st line DOC for moderate/high)

  • Given ______ PO or SQ, start with PO

  • Titrate to >15mg per week within 4-6 weeks (2.5 mg per week), 30mg weekly upper max limit

• SEs

  • ______ (monitor for liver dysfunction)

  • ______ (monitor CBC)

  • ______ (take supplemental folic acid 1mg PO daily)

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

    • Potential to ______ with ______ (avoid ______ administration ______)

weekly, LFTs increase, Suppression of blood counts, decreases folic acid, decrease MTX efficacy, Leucovorin, same day, PO/IV

Methotrexate (MTX)

• Contraindicated

  • Liver disease (severe)

  • ______

• Precautions

  • ______ (AKI or CKD)

  • ______

Pregnancy (X), renal elimination, liver dysfunction

Hydroxychloroquine (HCQ)

• Moderately effective ______

• ______

• SEs (well tolerated in general)

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

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

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

Sulfasalazine (SSZ)

• Onset (______)

• ______

• SEs

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

  • Serious:

    • Hepatitis- monitor ______

    • Leukopenia- monitor ______

    • ______

Takes a long time, safe in pregnancy, LFTs, CBC, Agranulocytosis

Leflunomide (LEF)

• SEs

  • Diarrhea is most commonly the limiting effect in treatment

  • ______

  • ______

  • Rash

  • Reversible alopecia

  • Rare but serious - interstitial ______ disease and ______

• C/I

  • ______ and carcinogenic in animal studies (______)

Liver toxicity, myelosuppression, lung, peripheral neuropathy, Teratogenic, do not use in pregnancy

KNOW IMAGE

Biologic DMARDs

• ______

  • Adalimumab

  • Etanercept

  • Infliximab

  • Certolizumab

  • Golimumab

• ______

  • ______ (IL-1 inhibitor)

  • ______ (IL-6 inhibitor)

  • ______ (B cell inhibitor)

  • ______ (co-stimultation inhibitor)

  • ______ & ______ (JAK/STAT kinase inhibitors) (technically not a biologic)

• ______ combine biologic DMARDS with each other

Anti-TNF Biologics, Non-TNF Targeting Biologics, Anakinra, Tocilizumab, Rituximab, Abatacept, Tofactinib, Baricitinib, do not

TNF Inhibitors → Anti-TNF Biologics

• TNF inhibitors: ______, ______, ______, ______, ______

• Common SEs (boxed warning):

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

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

  • ______: lymphoma, nonmelanoma skin cancer

• Warnings, precautions:

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

Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab, Infection, Opportunistic Infection, TB, must treat TB completely before starting, Cancer, CHF, transient neutropenia, blood

T-Cell Co-Stimulatory Blockade

• Abatacept Adverse Effects

  • ______ (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 ______)

Increased risk of infections, COPD, few, TB, TNFi

______

• Tocilizumab (Actemra®) SEs

  • Increase risk of infection and serious infection. (Can start if being treated currently for TB)

  • Increased risk of GI perforation

IL-6 Inhibitor

Interleukin-6 Inhibition

• ______ (______®) SEs

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

  • Increased risk of ______

Tocilizumab, Actemra, infection, infection, TB, GI perforation

______

• Rituximab Adverse Effects

  • Infections: reactivation of viral infections (hepatitis B)

B-Cell Depletion

B-Cell Depletion

• ______ Adverse Effects

  • Infections: ______ (______)

Rituximab, reactivation of viral infections, HepB

______

• Modest increase in risk of infection

IL-1 Antagonists

______

• Precautions: Infections

• Warnings

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

  • No in pregnancy

JAK Inhibitors

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 for VTE/PE

Treatment Goals

• Treat to ______

• Evaluate ______ for treatment success

target approach, every 3 months

Treatment Approach

• Combo Traditional DMARDs → DMARD non-biologic

• ______

  • TNF Inhibitors (Anti-TNF) +/- MTX

  • Non-TNF Biologic +/- MTX

• At this point >6 months

Preferred now over combo traditional DMARDs

KNOW IMAGE

Treatment Approach IMAGE (ENTER AFTER EACH FILLED BULLET POINT)

• Low → ______ > SSZ > MTX > LEF

  • Lack of Response/Improvement, Not at target (check up q3months) → Switch to ______ + ______ → give ______

• Moderate/High → ______ > LEF > SSZ > HCQ

  • Lack of Response/Improvement, Not at target (check up ______) → ______ → give ______

• 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 ______ e.g, ______ → ______ or ______

HCQ, MTX, maximize MTX dose, SQ

MTX, every 3 months, maximize MTX dose, SQ

add biologic DMARD, TNFi, JAK/STAT inhibitor, MTX

class of biologic, TNFi, non-TNFi, JAK/STAT inhibitor

Bridge Therapy

• Wait for DMARD to start → ______

3 months

RA Remission/Low Activity

• Approach if only on MTX → ______, ______

• If on MTX + biologic or JAKi, can start to ______ (not the ______)

decrease dose (taper), do not just stop, gradually discontinue MTX, biologic or JAKi