Rheumatoid Arthritis Flashcards
Rheumatoid Arthritis - Symptom Presentation
1) Diffuse pain (myalgias, arthralgias, arthritis
2) Variable time to symptom onset
3) Morning joint stiffness (gelling) lasting greater than 1 hour
4) Affected joints are swollen and inflamed
- Elbow
- Foot and ankle
- Hand and wrists (proximal interphalangeal and metacarpopalangeal joints)
- Hip
- Knee
- Shoulder
Rheumatoid Arthritis - Other contributing factors
1) Family hx of inflammatory disease such as:
- Autoimmune thyroid disease
- Multiple sclerosis
- Myasthenia gravis
- Rheumatoid arthrtitis
- Systemic lupus erythmatosus
2) Smoking is associated with increased disease activity
Vaccines to consider in patients receiving RA immunosuppressive therapy
Influenza vaccine - administer annually to all patients before and during DMARD therapy
Pneumococcal vaccine - Administer to all patients receiving biologic DMARDS, methotrexate, leflunomide and/or sulfasalazine before and during DMARD therapy
Hepatitis B - As above without the sulfasalazine
HPV - To all pts who meet recommendations from the CDC before and during DMARD therapy
Herpes Zoster - To all pts who meet recommendations from CDC before DMARD therapy and During if they are actively being treated with DMARD monotherapy or comination therapy but not if being treated with anti-TNF or non-TNF biologic agent
NSAID STEPS - Safety
- In patients at risk of or with existing cardiovascular disease, NSAID’s such as naproxen, ibuprofen and piroxicam are not associated with an increased risk of cardiovascular disease.
- all NSAID’s carry the risk of causing changes in renal function
- Patients with a greater risk of GI toxicity include:
- Elderly patients
- Patients with a history of GI bleeds
- Patients concurrently using anticoagulants, antiplatelet drugs, and/or systemic corticosteroids
NSAID STEPS - Tolerability
Dyspepsia
Prolonged bleeding
Dermatologic reactions
NSAID STEPS - Efficacy
- Available NSAIDs are equally effective, but individuals’ responses to agents will vary
- NSAIDs will reduce joint pain and swelling to some degree, but they will not modify the destruction or progression of RA
NSAID STEPS - Preference (Pearls)
- Celecoxib has fewer GI adverse events than other NSAIDs; however, it is no more effective at reducing pain and inflammation
- Adding misoprostol to an NSAID will decrease the risk of GI ulceration
- Adding a PPI to an NSAID will decrease nonulcerative symptoms
- If a patient does not respond to NSAID therapy (after an appropriate 14-28 day trial), providers should consider trying other NSAIDs before concluding therapeutic failure.
NSAID STEPS - Simplicity
- Widely available prescription and over-the-counter medications
- Once-daily formulations allow continuous analgesia
Corticosteroid STEPS - Safety
- Increased risk of osteoporosis and fracture
- Risk of symptoms of a psychiatric disturbance with increasing dose of corticosteroids
- Less than 40mg of prednisone/day 1-2%
- > 40mg of prednisone/day 5% incidence
- > 80mg of prednisone/day 20% incidence
Corticosteroid STEPS - Tolerability
Cataracts Dyslipidemia (high dose) Glaucoma Hirsutism Hyperglycemia Hypertension (high dose) Hypothalamic-pituitary-adrenal axis suppression Osteoporosis Pancreatitis (high dose) Weight gain
Corticosteroid STEPS - Efficacy
- Short-term (weeks), low-dose (less than 15mg of prednisone daily) corticosteroids are effective for symptoms flare
- Early initiation of corticosteroid and continuance at a low dose (less than 10mg of prednisone daily) reduce joint destruction and likelihood of clinical remission
- Higher corticosteroid doses ma be warranted to treat symptoms of sever or advanced disease (e.g., presence of vasculitis
- Intra-articular injections may be beneficial, but limit injections in joint to more than every 3-4 months
Corticosteroid STEPS - Preference (Pearls)
- Start appropriate calcium and vitamin D supplementation in all patients taking corticosteroid therapy
- Assess for bisphosphonate therapy
Corticosteroid STEPS - Simplicity
Once-daily fixed dose appears to be effective for symptom control and possibly slowing disease progression
Methotrexate STEPS - Safety
- Contraindicated in pregnancy and breastfeeding. Pregnancy should be avoided for at lease 3 months with men and at least one ovulatory cycle for women after discontinuing methotrexate
- Significantly diminishes the ability to generate an immune response
- Increased incidence of the following:
- any malignancy
- Lung cancer
- Melanoma
- Non-Hodgkins lymphoma
- Avoid in patient with the following:
- CrCl < 30ml/min
- Platelet count less the 50,000/mm3
- White blood cell count less than 3000/mm3
- Liver transaminases greater than 2 times the upper limit of normal
- Avoid concurrent use of NSAIDs in patients before or actively using high-dose methotrexate
Methotrexate STEPS - Tolerability
Abdominal cramping Anorexia Bone marrow suppression Hypersensitivity pneumonitis Increased aminotransferases Infections Nausea Stomatitis
Methotrexate STEPS - Efficacy
- Substantial treatment response in patients with RA
- Intense treatment strategy and dose may result in an increased chance of disease remission, but also an increased likelihood of having an adverse event or discontinuing therapy
- Consider changing to subcutaneous methotrexate in patient with an inadequate response to oral therapy secondary to increased bioavailability of the injectable formulation
- Proposed benefit of decreased chance of cardiovascular mortality
Methotrexate STEPS - Preference (Pearls)
- Considered first choice for DMARD therapy
- Adding a folic acid supplement decreases adverse events (folate deficiency increases risk of methotrexate toxicity)
Methotrexate STEPS - Simpliciy
Dosed as on subcutaneous injection or one oral dose weekly
Leflunomide (Brand)
Arava
Leflunomide STEPS - Safety
- Stevens-Johnson syndrome and toxic epidermal necrolysis
- May decrease defences against malignancy
- Women who wish to become pregnant or men who wish to farther a child should discontinue leflunomide use and us cholestyramine to achieve plasma (leflunomide) active metabolites less than 0.02 mg/L
- Patients with preexisting liver disease or aspartate aminotransferase/alanine transferase greater than 2 times thes upper limit of normal should not receive leflunomide
Leflnomide STEPS - Tolerability
- Alopecia
- Debilitating diarrhea
- Rash
- Severe hepatotoxicity
Leflunomide STEPS - Efficacy
- Available evidence shows leflunomide is comparable to methotrexate therapy
- May be added to methotrexate therapy to further improve symptoms, but at risk of hepatic toxicity
Leflunomide STEPS - Preference (Pearls)
An alternative for patients unable to tolerate or not responding to methotrexate therapy
Leflunomide STEPS - Simplicity
- 100mg by mouth daily for 3 days (loading dose) and then 20 mg by mouth once daily.
- dosage may be reduced (10 mg daily) for patients unable to tolerate full dose.
- Loading dose can be omitted for patients at high risk of hepatic or hematologic toxicities
Sulfasalazine (Brand)
Azulfidine
Sulfasalazine STEPS - Safety
- “Probably” safe for use in pregnancy; FDA pregnancy category B
- Avoid use in patients with:
- Platelet counts less than 50,000/mm3
- Liver transaminases greater than twice the upper limit of normal
- Acut hepatitis B/C
- Chronic hepatitis B, not receiving therapy
- Chronic hepatitis B, Child-Pugh Class C
- Chronic hepatitis C, Child-Pugh Class B or C
Sulfasalazine STEPS - Tolerability
- GI effects (may be lessened with enteric coated tablets
- A lupus-like syndrome has been reported in patients taking sulfasalazine
Sulfasalazine STEPS - Efficacy
Available data suggests that sulfasalazine is effective at modifying rheumatic disease activity, but data are less supportive of its effects on radiologic progression
Sulfasalazine STEPS - Preference (Pearls)
Alternative for women who are (or who are planning to become) pregnant
Sulfasalazine STEPS - Simplicity
- Twice-daily dosing
- May require 2-4 tablets per dose
Other considerations for synthetic DMARDs
Routine monitoring of CBC, hepatic transaminases, and creatinine when starting or adjusting DMARD therapy (methotrexate, leflunomide, sulfasalaine)
a) Every 2-4 weeks for first 3 months
b) Every 8-12 weeks until month 6
c) Every 12 weeks thereafter
Additional agents to consider in RA
a) Low disease activity and no poor prognosis factors;
1) Hydroxychloroquine
2) Minocycline (diagnosis less than 6 months)
b) Not recommended by the ACR
1) Azathioprine
2) Cyclophosphamide
3) Cyclosporine
4) D-penacillamine
5) Gold salts
Biologic DMARDs
Tumor necrosis factor (TNF) inhibitors
1) Adalimumab (Humira)
2) Certolizmab Pegol (Cimzia)
3) Enteracept (Enbrel)
4) Golimumab (Simponi)
5) Infliximab (Remicade)
TNF Inhibitors STEPS - Safety
- Increased risk of serious bacterial and/or fungal infections
- Associated with reactivation of tuberculosis
- May increase risk of malignancy, including melanoma, leukaemia, and lymphoma
- Linked with new or worsening heart failure and possibly death inpatients with heart failure
TNF inhibitors STEPS - Tolerability
- Headache
- Abdominal pain
- Injection site reactions
- Upper respiratory tract infection
- Infusion reactions (infliximab)
TNF Inhibitor STEPS - Efficacy
- First-line choice for biologic DMARDs on the basis of their ability to improve physical function and delay radiographic changes.
- Superior to synthethetic DMARDs with respect to radiographic outcomes
- Combination with methotrexate yields better outcomes than using TNF inhibitors as monotherapy
TNF Inhibitors STEPS - Preference (Pearls)
- The ACR generally recommends biologic DMARDs after insufficient response to nonbiologic DMARDs or in patients with high disease activity and reatures of poor prognosis
- The EULAR recommends biologic DMARDs after sufficient response to methotrexate or other nonbiologic DMARDs
- All patients receiving biologic DMARDs should be tested for (and treated for ) tuberculosis before starting RA therapy
- Treatment is expensive for patients without insurance or suboptimal coverage
- Infliximab should only be used in combination with methotrexate
TNF Inhibitors STEPS - Simplicity
- Doses may be given subcutaneously weekly (entaracept), every other week (adalimumab), or every 4 weeks (golimumab)
- Certolizumab is dosed subcutaneously every other week when initiating therapy and may be extended to every 4 weeks for maintenance therapy
- Infliximab is dosed intravenously every 9 weeks after completeing induction therapy at 0, 2, and t weeks. Interval may be decreased to every 4 weeks if necessary
Abatacept
Brand: Oencia
Biologic DMARD
Abantacept STEPS - Safety
- In patients with COP, abantacept has been linked with more adverse pulmonary effects.
- Increased risk of developing serious infections
Abantacept STEPS - Tolerability
- Acute infusion reactions
- Upper respiratory tract infections
Abantacept STEPS - Efficacy
- Should not be used in combination with other biologic DMARDs
- Effective for improrving RA symptoms but should not be introduced until failure of at least one TNF inhibitor
- Combination with methotrexate results in higher rates of remission than methotrexate monotherapy
Abantacept STEPS - Preference (Pearls)
The ACR recommendations suggest abatacept as an option for patients with moderate to sever disease for greater than 6 months or low disease activity with poor prognostic features who have not responded to methotrexate or another synthetic DMARD
Abantacept STEPS - Simplicity
- IV regimen: Once-monthy infusion after 0-, 2-, and 4-week induction
- Subcutaneous regimen: Initial IV infusion; then subcutaneous injection within 24 hours; and then weekly thereafter
Rituximab
Brand: Rituxan
DMARD
Rituximab STEPS - Safety
- Acute renal failure
- Cardiac arrhythmias
- Linked to fatal infusion-related adverse reactions
- Mucocutaneous reactions
- Progressive multifocal leukoencephalopathy
- Tumor lysis syndrome
Rituximab STEPS - Tolerability
- Arthralgias
- Henatologic effects may include lymphopenia, neutropenia, leukopenia, thrombocytopenia, and anemia
- Hyerphosphatemia
- Hypertension
- Hyperuricemia
Rituximab STEPS - Efficacy
Has shown efficacy as monotherapy or as add-on therapy to methotrexate
Rituximab STEPS - Preference (Pearls)
- Avoid use in patients who have not had an adequate trial with a TNF inhibitor
- Avoid administering live vaccines 3 months before or during treatment with rituximab
Rituximab STEPS - Simplicity
- A two-dose therapeutic course (separated by 14 days) every 24 weeks (may be readministered every 16 weeks, if needed)
- Consider using acetaminophen and antihistamine before infusion
Tocilizumab
Brand: Actemra
DMARD
Tocilizumab STEPS - Safety
- Serious bacterial, fungal, and viral infections reported with use
- All patients should receive monitoring for tuberculosis before and after starting tocilizumab therapy
- GI perforation reported with concomitant use of tocilizumub and NSAIDs, corticosteroids, and/or methotrexate
- Avoid use in patients with the following
- Absolute neurophil count less than 2000/mm3
- Platelet count less than 100,000/mm3
- Aminotranferases greater than 1.5 times the upper limit of normal
Tocilizumab STEPS - Tolerability
- Dyslipidemias reported
- Hypersensitivity reactions starting with the second to fourth infusion
- Neutropenia or thrombocytopenia
- Transaminase elevations
- Upper respiratory tract infections
Tocilizumab STEPS - Efficacy
- Effective treatment option for patients not responding or inadequately responding, to methotrexate therapy
- Used in combination with methotrexate therapy
Tocilizumab STEPS - Preference (Pearls)
FDA approved for patients with an inadequate response to one or more TNF inhibitors
Tocilizumab STEPS - Simplicity
Intravenous infusion every 4 weeks
Anakinra
Brand: Kineret
DMARD
Anakinra STEPS - Safety
- Increased risk of neutropeniz when combined with TNF inhibitors
- High doses are associated wth increased risk of serious infection
Anakinra STEPS - Tolerability
- Diarrhea
- Influenza-like reaction
- Injectioni site reactions
Anakinra STEPS - Efficacy
Effective for decreasing RA symptoms, but not as effective as TNF inhibitors
Anakinra STEPS - Preference (Pearls)
- Do not administer live vaccines to patient receiving anakinra
- Not included in the ACR recommendations because of limited data available in the literature and not recommended in the EULAR guidelines because of less clinical efficacy in trials
Anakinra STEPS - Simplicity
Once-daily subcutaneous injection
