IC16: Management of RA

Question 1

State the peak incidence of RA and which gender is it most common in

Answer 1

Peak: 40-50yo
Most common in females (~3x)

Question 2

State 3 risk factors for RA

Answer 2

Family history 3x higher in 1st degree relative, 2x higher is 2nd deg relative
Genetic predisposition: HLA-DRB1 gene
Smoking

Question 3

RA increases the risk of developing other chronic diseases such as…

Answer 3

1. CVD
2. Lung disease
3. Psychiatric disorders
4. osteoporosis
5. Malignancies

Question 4

List 4 inflammatory cytokines involved in RA pathophysiology

Answer 4

• IL-1
• IL-6
• IL-17
• TNF-a

Question 5

List the clinical presentations of RA

Answer 5

1. Pain, swelling, erythematous (red) & warm
2. Early morning stiffness > 30min
3. Symmetrical polyarthritis (may be unilateral at first)
4. Systemic symptoms (fatigue, fever, weight loss, depression, generalised aching/stiffness)
5. Extra-articular complications

Question 6

List 2 complications of **chronic RA **

Answer 6

1. Deformities- swan neck, boutonneire, Z-shaped thumb etc…
2. Loss of physical function & ability to carry out ADL

Question 7

List the extra articular complications of RA. State the organ and type(s) of complications

Answer 7

• Eye: Sjogren’s syndrome
• Heart: Coronary Artery Disease
• Haematology: Felty’s syndrome
• Lungs: pleural effusion, interstitial lung disease
• Renal: glumorulonephritis
• Skin: Rheumatoid nodules
• Vascular: Rheumatoid vasculitis, peripheral vascular disease

Question 8

List the laboratory findings found in a patient with RA

Answer 8

1. Autoantibodies: RF+, anti-ccp +ve
2. Acute phase response: Elevated ESR, CRP
3. FBC: decreased Hct, elevated platelets &WBC
4. Radiologic(X-ray/MRI): Narrowing of joint space, erosion (around joint margin), hypertrophic synovial tissue (due to pannus formation)

Question 9

Is radiologic imaging required for the diagnosis of RA?

Answer 9

No. Usually done at baseline for monitoring disease progression than diagnosis. Early onset damage usually not observable

Question 10

Describe the criteria for RA diagnosis

Answer 10

• RA is diagnosed using history, PE, labs, radiographs
  & Must fulfill at least 4 of the following:
• Early Morning Stiffness > 1 hour x > 6 weeks
• Swelling of > 3 joints x > 6 weeks
• Swelling of wrist/ MCP/ PIP joints x > 6 weeks
• Rheumatoid nodules
• +ve RF and/or anti-CCP tests
• Radiographic changes

Question 11

List the goals of treatment for RA

Answer 11

1. Achieve remission or low disease activity
   * for at least 6mths, using:
   * Boolean 2.0 criteria (remission)
   * Index based definition of SDAI/CDAI/DAS 28
2. Achieve maximal functional improvement
3. Stop disease progression
4. Prevent joint damage
5. Control pain

Question 12

List the drugs used to treat RA

Answer 12

1. NSAIDs
2. Glucocorticoids
3. DMARDs

Question 13

List 4 csDMARDs

Answer 13

Methotrexate, sulfasalazine, leflunomide, hydroxychloroquine

Question 14

List 3 TNF-a inhibitors

Answer 14

Infliximab, etanercept, adalimumab

Question 15

List an IL-6 receptor antagonist

Answer 15

Tocilizumab

Question 16

State 2 tsDMARDs

Answer 16

Tofacitinib, baricitinib

tsDMARDs = JAK inhibitors

Question 17

Describe the place in therapy of NSAIDs for the treatment of RA

Answer 17

1. Does not alter course of diseaes
2. Used as adjunct to DMARDs to relieve pain & minor inflammation

Question 18

Describe the place in therapy of glucocorticoids for the treatment of RA

Answer 18

1. Used as bridging therapy with DMARDs
2. Used as continuous low-dose therapy for difficult to control patients, **but not recommended due to SE ** of many DMARDs
3. IA injections used to control flares

Question 19

List at least 5 adverse effects of glucocorticoids

Answer 19

1. Increased CV risk
2. Cataract glaucoma
3. Gastric ulcer (+ nsaids)

Endocrine
4. hyperglycemiaImpaired glucose metabolism, insulin resistance, b-cell dysfunction
5. Weight gain/obesity
6. Fluid retention, edema
7. Cushing syndrome

Osteoporosis/osteonecrosis

Question 20

Which of the RA drug classes alter disease progression, and which does not?

Answer 20

Alter: DMARDs
Does not: NSAIDs, glucocorticoids

Question 21

Describe the benefits of DMARDs

Answer 21

DMARDs alter disese progression via:
* Slow/prevent radiographic joint dmg
* Improve physical function
* Lower ESR/CRP

Question 22

When should DMARDs be initiated after a diagnosis of RA?

Answer 22

Start ASAP after diagnosis

Question 23

State the first-line DMARD used for RA treatment

Answer 23

Methotrexate (Sulfasalazine/leflunomide if MTX is CI or not tolerated)

Question 24

Which class of medication is commonly given when initating/changing DMARDs?

Answer 24

MTX + Glucocorticoids (short term), taper & discontinue ASAP to avoid long term SE)

Question 25

How often should RA treatment be monitored in active disease?

Answer 25

If no improvement by 3mth or target not reached by 6 mth

Question 26

# According to ACR 2021, Which DMARD is preferred in moderate to high disease activity for DMARD-naive patients

Answer 26

Moderate to high disease activity

Question 27

# According to ACR 2021, Which DMARD(s) are preferred in low disease activity for DMARD-naive patients?

Answer 27

1. Hydroxychloroquine (better tolerated) 2. Sulfasalazine (less immunosuppressive vs MTX) 3. MTX > leflunomide (greater dosing flexibility & lower cost)

Question 28

State the dosing for MTX monotherapy | Initiation, dose increment, target dose, max dose

Answer 28

1. **Initiation dose**: 7.5 mg ONCE weekly 2. **Dose increment** 2.5 – 5 mg/week every 4-12 weeks based on response 3. **Target dose**: 15 mg/week within 4-6 weeks of initiation 4. **Max** 25 mg/week

Question 29

State the dosing for short term glucocorticoid therapy to MTX | Initiation dose, duration, when to discontinue?

Answer 29

Prednisolone ≤7.5mg/d x 3mths. **Taper & discontinue:** within 3 months OR **Discontinue** if bDMARD/tsDMARD started

Question 30

Compare & contrast between the csDMARDs | MOA, PK, dose adjustment, CI, DDI, SE, pregnancy, monitoring, labs

Answer 30

Refer to IC16 RA, slide 21

Question 31

Which DMARD(s) should be avoided in pregnancy? Which can be used in pregnancy?

Answer 31

Avoid: MTX & Leflunomide Can use: Sulfasalazine, hydroxychloroquine

Question 32

For patients on MTX but not at target, what should be done?

Answer 32

* Add bDMARD or tsDMARD (bMARD > tsDMARD) * Add hydroxychloroquine & sulfasalazine (triple therapy; less risk of adverse events & lower cost)

Question 33

For patients on bDMARD/tsDMARD but not at target, what should be done?

Answer 33

Switch to bDMARD or tsDMARD **of a different class**

Question 34

Compare & contrast between bDMARDs and tsDMARDs | 1) ROA, 2) MOA

Answer 34

**bDMARD**: * ROA: SC injection/IV infusion * MOA: bind to cytokines or their receptorrs to downregulate/inhibit fxn, this reduces immune & inflammatory response **tsDMARD**: * ROA: Oral * MOA: binds to JAK proteins inside cells, prevent JAKs from transphosphorylating the associated cytokine & growth factor receptor

Question 35

State the adverse effects of bDMARDS & tsDMARDs

Answer 35

* **Injection site / infusion reactions**: acute vs delayed (not seen in JAK-i due to PO adm) * **Myelosuppression**: need to monitor CBC with WBC differentials & platelet count * **Infections**: URTI, TB, hepatitis, opportunistic infections -> pre-DMARD screening & Tx needed * **Malignancy** risk: similar risks between bDMARD & tsDMARD? -> shared decision-making needed * **Autoimmune diseases**: SLE or lupus-like syndromes, demyelinating peripheral neuropathies * **Cardiovascular diseases**: HF (avoid TNF-a, inhibitors in NYHA class III & IV), HTN, * **Hepatic effects**: Increased aminotransferase -> monitor LFT * **Metabolic effects**: Hyperlipidemia -> monitor lipid panel * **Pulmonary diseases:** Pulmonary toxicity -> use with caution in interstitial disease * **Gastrointestinal perforation**: esp with IL-6 inhibitors & JAK inhibitors (risk factors: diverticulitis, > 65yo, GC use, NSAID use) / also reported in Rituximab (ave onset ~ 6 days, range 1-77 days) -> evaluate abdo pain or repeated vomiting * **Thrombosis**: esp with JAK inhibitors & IL-6 inhibitors (avoid in patients w Hx of thrombotic events)

Question 36

State the principles for the selection of bMARD/tsDMARDs

Answer 36

1. **Do not use** > 1 bDMARD/tsDMARD at the same time 2. Consider contraindications during selection * Hypersensitivity to components of the formulation * Severe infections e.g. sepsis, TB, opportunistic infections -> consider vaccination against diseases with vaccination before initiating DMARDs * HF (for TNF-a inhibitors) 3. Anti-drug antibodies (ADA) may occur with TNF-a inhibitors --> loss of efficacy 4. Switch to a bDMARD w a different MOA when one fails

Question 37

List 4 DMARDs to be avoided in heart failure

Answer 37

To avoid TNF-a inhibitors (IGAE) - Infliximab, golimumab, adalimumab, etanercept

Question 38

Explain if bDMARDs or tsDMARDs are preferred. Explain why

Answer 38

bDMARDs are preferred. tsDMARDs eg. tofacitinib has higher risk for MACE & Malignancy compared to TNF-a inhibitors

Question 39

State the risk factors that contribute to MACE & malignancy when using a JAK-inhibitor/tsDMARD

Answer 39

**1. Cardiovascular risk factors**: > 65 yo, Hx for past/current smoking, Obesity **2. PMH of DM, HTN**: Risk factors for malignancy, Hx for past/current malignancy **3. Risk factors for thromboembolic events**: PMH of MI, HF, Inherited blood clotting disorders, blood clots, Use of CHC, HRT, Undergoing major surger, Immobility

Question 40

List 3 screening parameters that should be performed before initiating bDMARDs/tsDMARDs

Answer 40

**1. Pre-treatment screening** * Tuberculosis (latent/active): start after completing anti-TB Tx * Hepatitis B & C: avoid if untreated disease detected **2. Vaccination required before initiation** * Pneumococcal * Influenza * Hepatitis B * Varicella zoster / Herpes zoster **3.Laboratory screening/monitoring** * CBC w differential white count & platelet count * LFT (ALT, AST, bilirubin, ALP) * Lipid panel * SCr

Question 41

How should DMARDs be discontinued after patients are at target for ≥ 6mths? | For monotherapy, triple therapy & MTX + bDMARD/tsDMARD

Answer 41

**Mono:** Dose reduction gradually **Triple:** Gradual discontinuation of sulfasalazine recommended over hydroxychloroquine (for lower adverse events & better tx persistence) **MTX + bDMARD/tsDMARD**: gradual discontinuation of MTX is recommennded for better disease control | Abrupt discontinuation can lead to flares

Question 42

State 3 nonpharmacological interventions for RA

Answer 42

**1. Rest inflamed joint**/use splints to support joints & reduce pain- do not promote rest when there is no ongoing active disease as this can lead to acute flares **2. Physical activity & exercise**- ROM exercises, exercises to incr muscle strength, aerobic exercise, avoid high intensity weight bearing exercises **3. PT/OT referral**- supervised/tailored exercise **4.Nutritional & dietary counselling** **5. Psychosocial interventions**: CBT for enhancing self efficacy % QOL **6. Patient education**- evidence based info abt diseaes & Tx; expectations of tx; correct misconceptions