DERM IE2 MATERIAL: RA

etilogy and pathogenesis of RA

• autoimmune disease

• systemic inflammation

• need to treat to prevent progression

key immune cells, cytokines, and pathways involved

• T cells

• B cells

• Pro-inflammatory cytokines (TNF, IL-1, IL-6)

• JAK pathway

RA

• inflammatory polyarthritis

• affects usually smaller joints of hands and feet

RA characterized by

• RF, ACPA = highly specific

• inflammation, pannus

• deformity

• extra-articular involvement

clinical s/sx

• slow onset but progressive

• fever, malaise, arthralgia, weakness

• stiffness worse in morning → activity can decreaeses it

• synovitis

• impacts activities of daily living

• most common joint involvement

• other large joint involvement

• most common joint involvement

  • hands

    • proximal interphalenfial joint (PIP)

    • metacarophalengeal joint (MCP)

• other large joint involvement

  • knee

  • hip

  • elbow

  • shoulders

extra-articular involvement

• untreated RA → can affect organs

• rheumatoid nodules

• pulmonary

• ocular

• cardiac

• neurologic

• other

  • depression, anxiety, anorexia, weight loss

Diagnosis of RA: total score indicating RA

6 or higher

diagnosis of RA

• joint involvement

• serology

• acute phase reactants

• duration of sx

• joint involvement

  • # and types of joints

• serology

  • RF - can be present in other diseases

  • ACPA - more specific for RA

• acute phase reactants

  • CRP (C-reactive Protein)

  • ESR (erythrocyte sedimentation rate)

• duration of sx

  • ≥ 6 weeks

when should recognition and diagnosis of RA start?

early

what is treatment for ALL patients w/ RA?

DMARD (disease modifying anti-rheumatic drugs)

baseline testing before starting DMARDs

• CBC (cell count)

• LFTs (liver function)

• BUN/SCr (renal function)

• TB testing (to make sure no latent TB)

  • if TB + and is on DMARD → TB can get activated → NOT GOOD

selection of DMARD based on

• severity and stage of RA

• pt preference

• insurance coverage

• comorbid conditions

what is used for bridging therapy w/ DMARDs?

NSAIDs or glucocorticoid therapy = only for short term sx relief

treat to target

• achieve + maintain tight control of disease activity = remission or low disease state activity

• evaluate every 3 months

treatment failure

lack of remission or low disease activity after 3 - 6 months of DMARDs at optimal dosing

CDAI Score based on severity of disease activity

higher # = worse

non-pharmacological therapy

• exercise

• massage

• smoking cessation → smoking = pro-inflammatory

• stress reduction

• diet

• counseling

• physical therapy

• surgery = last resort

DMARD naive

pts w/ RA who have not had DMARD yet

non-biologic DMARD (conventional synthetic - csDMARD)

• Methotrexate (Trexall)

• HCQ

• Sulfsalazine

• Leflunomide

• can be combine with each other (up to 3)

T or F: biologic and biologic CANNOT be combined

True

Methotrexate (MTX)

• action

• role

• dosing

• SEs

• precautions

• renal adjustment?

• action

  • anti-inflammatory and immunosuppressive

• role

  • 1st line DOC for moderate/high RA

• dosing

  • given weekly (PO or SQ)

• SEs

  • fatigue

  • alopecia

  • GI upset

• precautions

  • renal elimination, liver dysfunction

• renal adjustment?

  • yes

MTX SEs labs

• LFT increases

• suppression of blood counts → monitor CBC

• decreases folic acid → take supplemental folic acid (Leucovorin)

  • avoid same day admin as it can decrease MTC efficacy

CI of MTX

• severe liver disease

• pregnancy (Category X)

  • females → stop at least 1 ovulatory cycle

  • males → stop for at least 3 months

Hydrochloroquinolone (HCQ)

• action

• role

• efficacy SEs

• monitoring renal adjustment?

• action

  • anti-malarial agent

• role

  • effective alone for mild RA

• efficacy

  • no response within 6 months → treatment failure

• SEs

  • well tolerated

  • rare: retinal toxicity

• monitoring

  • eye exam done at baseline and every 5 years thereafter

• renal adjustment?

  • no

what meds for unresponse RA?

HCQ + MTX and/or Sulfasalazine

Sulfasalazine (SSZ)

• action

• role

• onset

• pregnancy

• SEs

• monitor

• renal adjustment?

• action

  • immunosuppressive and anti-inflammatory

• role

  • commonly used in combo w/ MTX or if MTC can’t be used

• onset

  • initial: 6 - 12 weeks

  • full effect: 23 weeks

• pregnancy

  • safe

• SEs

  • GI upset, rash

  • serious: hepatitis, leukopenia, agranulocytosis

• monitor

  • LFTs, CBCs

• renal adjustment?

  • yes

Leflunomide (LEF)

• action

• role

• onset

• SEs

• pregnancy

• monitoring

• renal adjustment?

• action

  • pyramidine synthesis inhibitor

• role

  • not commonly used

  • increased risk of liver toxicity when in combo w/ MTX

• onset

  • 4 - 8 weeks

• SEs

  • diarrhea

• pregnancy

  • CI → teratogenic and carcinogenic

  • requires cholestyramine for 11 days to sequester drug

• monitoring

  • LFTs, CBC

• renal adjustment

  • no

Biologic DMARDs: anti-TNF

• Adalimumab

• Etanercept

• Infliximab

• Certolizumab

• Golimumab

anti-TNF Biologics

• action

• onset

• SEs

• warning/precautions

• action

  • target TNF-alpha

• onset

  • 2- 4 weeks for improvement

  • 3 - 6 months for significant benefit

• SEs

  • infection

  • opportunistic infection (TB)

  • cancer

• warning/precautions

  • not recommended in pts w/ CHF, neutropenia, blood dyscrasias, s

  • screen for TB → treat first

Biologic DMARDs: non-TNF targeting

• Anakinra

• Tocilizumab

• Rituximab

• Abatacept

• Tofacitinib and Baricitinib

Abatacept

• MOA

• onset

• ADE

• MOA

  • T cell costimulatory blockade

• onset

  • 3 months, continuous improvement within 1st year

• ADE

  • increased infection risk, opportunistic infections

    • if TB positive → can use abatecept and TB treatment at same time (unlike anti-TNFs)

    • pneumonia (esp w. COPD)

Tocilizumab

• MOA

• onset

• SEs

• MOA

  • IL-6 inhibitor

• onset

  • 4 - 8 weeks (1 - 2 months)

• SEs

  • increased risk of infection (can start if being treated for TB)

  • increased risk of GI perforation

Rituximab

• MOA

• role

• onset

• ADE

• MOA

  • B-cell depletion

• role

  • option after TNF inhibitors or unable to take TNF inhibitors

• onset

  • 3 months for effect

  • last 6 months to 2 years

• ADE

  • infusion reactions

  • reactivation of viral infections (Hep B)

  • complete immunizations prior to therapy; avoid live vaccines

Anakinra

• MOA

• role

• onset

• SEs

• MOA

  • IL-1 antagonist

• role

  • used alone or in combo w/ non-biologic DMARDs

• onset

  • 2 - 4 weeks

• SEs

  • injection site reactions

  • infection risk (when combined w/ csDMARDs)

Tofacitinib and Upadacitinib

• MOA

• role

• precautions

• warnings

• pregnancy

• MOA

  • JAK inhibitors

• role

  • approved in RA pts who failed MTX

• precautions

  • infections

  • CBC monitoring, LFTs

• warnings

  • thrombosis (VTE/PE)

  • infections

  • malignancies

• pregnancy

  • no

low disease activity (mild) treatment approach

• conventional DMARD (1st line) → HCQ > SSZ > MTX > LEF

• no improvement (check q 3 months)

  • switch to MTX

  • maximize MTX

  • give SQ

• still no improvement

  • add biologic OR STAT + MTX (1st line)

  • triple conventional DMARD (2nd line)

• still no improvement

  • different class of biologic (TNFi) → non-TNFi or JAKi

  • add glucocorticoid → change DMARD 1st

  • IA steroid injections → change DMARD 1st

moderate/high disease activity: treatment approach

• conventional DMARD (1st line) → MTX > LEF > SSZ > HCQ

• no improvement (check q 3 months)

  • maximize MTX

  • give SQ

• still no improvement

  • add biologic OR STAT + MTX (1st line)

  • triple conventional DMARD (2nd line)

• still no improvement

  • different class of biologic (TNFi) → non-TNFi or JAKi

  • add glucocorticoid → change DMARD 1st

  • IA steroid injections → change DMARD 1st

bridge therapy

• glucocorticoids (PO and IA)

  • guidelines not recommended

• NSAIDs

• for induction periofs, flares, during changes in regimens

• no disease modifying activities

• only for sx management

RA remission/ Low activity

• tapering/dc

• approach if only on MTX

• approach on triple DMARD

• approach if on MTX + biologic or JAKi

• tapering/dc

  • stable (> 6 months)

• approach if only on MTX

  • taper, do not stop

• approach on triple DMARD

  • discontinue SSZ

• approach if on MTX + biologic or JAKi

  • gradually dc MTX