Rheumatoid Arthritis/Osteoarthritis

Sarah DaoudFlorida A&M University College of Pharmacy and Pharmaceutical Sciences10/02/13Seminar: Disease Presentation

Objectives

Discuss the prevalence, epidemiology, risk factors, and pathophysiology of RA/OA.

Discuss the signs and symptoms, diagnosis, and treatment of RA/OA.

Assess treatment of disease states in special populations.

Evaluate the role of the pharmacist in the overall approach of these conditions.

Discuss key components of RA/OA which would serve as educational points for patients and healthcare practitioners.

RHEUMATOID ARTHRITIS

Prevalence

RA is the most common form of autoimmune arthritis affecting more than 1.3 million Americans.

Women encompass 75% of individuals diagnosed with this disease.

1-3% of women may get RA in their lifetime.

Usual occurrence is in individuals between 40-60 years of age.

Epidemiology

RA does not have any racial inclination and can occur at any age.

Research has shown, this disease has a genetic predisposition and diagnosis may be necessitated by certain unknown environmental exposures.

Major histocompatibility complex (MHC) molecules located on T-lymphocytes play a major role in patients with RA.

Human lymphocyte antigen (HLA) typing can characterize these molecules and assess the risk of RA in those with presence of antigens on MHC molecules.

Risk Factors

Sex (Female)

Family history

Older age

Silicate exposure

Smoking

Consuming 3 or more cups of coffee/day (esp. decaffeinated coffee)

Pathophysiology

Signs and Symptoms

Morning stiffness lasting hours (sometimes whole day)

Fatigue

Weakness

Low-grade fever

Loss of appetite

Joint pain

Firm lumps

***Joint involvement tends to be symmetrical

Diagnosis

Non-pharmacological Treatment

Rest

Occupational therapy

Physical therapy

Use of assistive devices

Weight reduction

Surgery

Pharmacological Treatment

Pharmacological Treatment Agents used for pain and inflammation

Drug Dosage Adverse Effects

Warnings/Contraindications

Notes

Ibuprofen (Motrin, Advil)

->200-400mg Q6-8H (mild to moderate pain)->600-800mg Q6-8H; max 3.2g/d (moderate pain or inflammation)

-Dyspepsia-Heartburn-Increase BP-GI bleeding

-NSAIDS have BBW of increased risk of adverse CV thrombotic events; contraindicated for CABG perioperative pain; increased GI adverse events (ulceration, bleeding, perforation)-Contraindicated in pregnancy 3rd trimester.

-Avoid use in advanced renal disease.

Celecoxib (Celebrex) ->100-200mg BID -Diarrhea-Nausea

-Warnings are the same as NSAIDS.-Contraindicated with sulfa allergy.

-Lower risk of GI complications.-Max 400mg

Prednisone (Rayos, Prednisone Intenson)

->Initial 5-60mg daily indicated for acute inflammation->Can use twice daily dose every other day to decrease adrenal suppression.

-Fluid retention-Stomach upset-Increase appetite.-Hyperglycemia-Osteoporosis-Muscle wasting

-Contraindicated with live vaccines, systemic lung infections.

-Must assess bone density if used long-term.-Must taper dose off.

Pharmacological Treatment Non-biologic Disease-modifying anti-rheumatic drugs (DMARDS)Drug Dosage Adverse Effects Warnings/

ContraindicationsNotes

Methotrexate (Rheumatrex, Trexall)

-folate antimetaboline that inhibits DNA synthesis

->7.5-22.5mg/week

-N&V-Diarrhea-GI upset-Anorexia-Reddening of skin

-BBW: fetal death or congenital abn.; hepatotoxicity; BMS; malignant lymphomas; acute renal failure.-Contraindications: pregnancy; alcoholism; chronic liver disease; blood dyscrasias

-Never dose daily for RA (dose can be split into smaller doses taken over 12-36 hours)-Pregnancy category X

Hydroxychloroquine (Plaquenil)

->Initial: 400-600mg/day->Maintain: 200-400mg/day

-Decreased visual acuity-Photophobia-Blurred vision-Corneal deposits

-Can cause neuromyopathy with long-term use; SJS; alopecia; pigmentation of skin and hair (bleaching)

-Used in mild RA-Take with food or milk-Mainly eliminated by the kidney

Sulfasalazine (Azulfidine, Sulfazine)

-5-aminosalicyclic acid derivative

->500-1,000mg BID; max 3g/day

-Headache-Anorexia-Dyspepsia-GI upset

-Contraindications: pts with a sulfa or salicylate allergy, GI or GU obstruction-Can cause reversible oligospermia; folate deficiency d/t impaired folate absorption

-Take with food and 8oz of water to prevent crytalluria-Can cause yellow-orange discoloration of skin/urine-May give 1mg/day folate supplement

Pharmacological Treatment Non-biologic DMARDS cont.

Drug Dosage Adverse Effects

Warnings/Contraindications Notes

Minocycline (Dynacin, Minocin, Solodyn)

->100mg BID

-GI upset-N&V

-May cause SJS and decreased LFTs

-Used in mild RA-Pregnancy Cat. D-Do not use in children 8 yoa or younger.

Leflunomide (Arava)

-> 100mg x3days, then 20mg daily

-Diarrhea-URTIs-Rash-Alopecia

-BBW: women of childbearing potential should not use age until pregnancy is excluded; hepatotoxicity

-Must have negative pregnancy test before starting and use 2 forms of birth control.-If pregnancy wanted, must wait 2 yrs after discontinuation or give cholestyramine.-Can use with or without methotrexate-Pregnancy Cat. X

Pharmacological Treatment Biologic agents- TNFalpha inhibitors

BBW: serious infxs; lymphomas; malignancies; perform test for latent TB before initial therapy.

Contraindication: sepsis Can cause worsening or new onset Heart Failure; hep. B

reactivation; demyelinating disease. Do not give with other biologics or live vaccines SE: infections and injection site reactions Administration: do not shake; require refrigeration; allow to

reach room temp. before injecting These agents are usually add-on therapy to methotrexate

Pharmacological Treatment Biologic DMARD agents- TNFalpha inhibitors

Drug Dosage Notes

Etanercept (Enbrel) ->50mg SC once/week

Adalimumab (Humira) ->40mg SC every other week -If not taking MTX, can increase dose to 40mg SC weekly

Infliximab (Remicade) ->3mg/kg IV at weeks 0,2,6 and then Q8W can increase to 10mg/kg

-Higher dose=increase infx risk-Infusion reaction: hypotension, fever, chills, pruritis (benefit from APAP/ antihistamine/ steroids as pre-treatment)-Delayed hypersensitivity rxn 3-10d after admin (fever, rash, myalgia, HA, sore throat)

Certolizumab pegol (Cimzia) ->400mg SC at weeks 0,2,4 and then 400mg Q4W

-Can maintain at 200mg every other week

Golimumab (Simponi) ->50mg SC once/month -Give with MTX

Pharmacological Treatment Biologic response modifiers

Drug Dosage Adverse Effects

Warnings/Contraindications

Notes

Rituximab (Rituxan)-depletes CD20+ B cells

->1g IV day 1 and 15 @50mg/hr (can increase to 400mg/hr if no rxn)

-Fever-Chills-Angioedema-BMS-Abdominal pain

-BBW: severe and fatal infusion related reactions; PML due to JC virus infection; tumor lysis syndrome leading to acute renal failure and dialysis; SJS, TEN can occur-Warnings: serious infxs

-Pre-medicate with a steroid-Used with MTX-Do not give with live vaccines or other biologics-Screen for latent TB before initiating

Anakinra (Kineret)-IL-1 receptor antagonist

->100mg SC daily -Headache-Infections-BMS-Injection site rxn

-Warnings: serious infxs -Do not give with live vaccines or other biologics-Screen for latent TB before initiating

Abatacept (Orencia)-Selective T cell costimulation blocker

->500mg-1,000mg IV based on body wt; given over 30min

-Headache-Infections-Injection site rxn

-Warnings: serious infxs -Do not give with live vaccines or other biologics-Screen for latent TB before initiating

Pharmacological Treatment

Drug Dosage Adverse Effects

Warnings/ Contraindications Notes

Tofacitinib (Xeljanz)

-inhibitor of Janus kinase (JAKs)

->5mg PO BID

-URTIs-Diarrhea-Headache

-BBW: can cause serious infections, lymphomas and other malignancies; screen for latent TB-Can cause GI perforation-Not recommended in severe hepatic impairment-Do not give with live vaccines

-Do not use with potent 450 inducers; reduce dose to 5mg daily w/ potent 3A4 and 2C19 inhibitor.-Do not use with biological DMARDs or potent immunosuppressants-Monitor neutrophil count, hemoglobin, and lymphocyte count

Kinase Inhibitors

OSTEOARTHRITIS (AKA: Degenerative Joint Disease)

Prevalence

An estimated 15.8 million adults display symptoms of OA

Prevalence increased with age E.g. Those aged 75-79 years, 85% have OA of the hands,

whereas those 45 year and younger, only 1/5th have OA of the hands.

Severity also increases with age

Women are more affected

Knee OA twice as prevalent in black opposed to white women

Epidemiology

Most prevalent of the rheumatic diseases

Responsible for disability and loss of productivity

OA at some skeletal sites occurs in nearly everyone 75 years and older

½ million symptomatic cases of idiopathic OA occur yearly in the US white population

Risk Factors

Obesity

Repetitive motion (constant stress on hand, knee, etc.)

Joint injury

Genetics

Type and intensity of physical activity

Pathophysiology

Signs and Symptoms

Pain with motion

Joint stiffness lasting <30min (usually in the morning)

Joint: Tenderness Crepitus Enlargement

Diagnosis

3 Goals: Differentiate between

primary or secondary OA

Clarify joints involved Assess prior therapies

Diagnostic Parameters: OA of knee-

Refer to signs and symptoms

Age >50yo OA of hand-

Heberden’s node (2 or more out of 10)

OA of hip- Normal ESR Osteophytes and joint

space narrowing on on X-ray

Non-pharmacological Treatment

Exercise programs (aquatic)

Weight loss

Patient education for self-management

Wedged shoe insoles

Rest

Braces (symptomatic relief)

Pharmacological Treatment Pain Relief (primary indication for pharmacological treatment)

Drug Dosage Adverse Effects

Warnings/ Contraindications

Notes

Acetaminophen (Tylenol)

->650-1000mg PO Q6H

-Constipation-Headache-Vomiting

-Contraindications; hepatic impairment-Alcoholism can increase hepatic injury

-For mild to moderate pain-Max 4g/day

Tramadol (Ultram) ->initial: 25mg/day, increase by 25mg increments in separate doses every 3 days->maintain: 50-100mg PO Q4-6H

-Flushing-Constipation-Headache-Nausea-Xerostomia

-Contraindications: hypercapnia, severe bronchial asthma, acute intoxication with alcohol, narcotics, etc.

-For moderate to severe pain-Max 400mg/day-Adjust dose for renal impairment

Pharmacological TreatmentOpioid Analgesics

Drug Dosage Adverse Effects

Warnings/ Contraindications

Notes

Codeine sulfate ->15-60mg PO Q4H

-Somnolence-Dyspnea-Hypotension-Bowel obstruction-Pancreatitis

-Contraindications: bronchial asthma, hypercarbia-Has potential for abuse-May cause diminished biliary and pancreatic secretions-May prolong GI obstruction

-For mild to moderate pain-Max dose: 360mg/day

Oxycodone hydrochloride

->5-15mg PO Q4-6H

-Constipation-Nausea-Somnolence

-BBW: fatal respiratory depression-Contraindications: bronchial asthma, hypercarbia

-For moderate to severe pain

Pharmacological TreatmentNSAIDSDrug Dosage Adverse

EffectsWarnings/ Contraindications Notes

Aspirin ->Up to 3g/day in divided doses

-GI upset-Bleeding-GI ulcer

-Caution with bleeding disorders, renal or hepatic disease

-May take with food or milk

Ibuprofen(Advil)

->1200 to 3200 mg/day PO in 3-4 divided doses

-Dyspepsia-Heartburn-Increase BP-GI bleeding

-NSAIDS have BBW of increased risk of adverse CV thrombotic events; contraindicated for CABG perioperative pain; increased GI adverse events (ulceration, bleeding, perforation)-Contraindicated in pregnancy 3rd trimester.

-Avoid use in advanced renal disease

Naproxen(Aleve)

->250-500mg PO BID

-Edema-Abdominal pain-Tinnitus -Dyspnea

--NSAIDS have BBW of increased risk of adverse CV thrombotic events; contraindicated for CABG perioperative pain; increased GI adverse events (ulceration, bleeding, perforation)

-Max 1500mg/day for up to 6 mo

Celecoxib (Celebrex)

->100mg BID or 200mg daily

-Diarrhea-Nausea

-Warnings are the same as NSAIDS.-Contraindicated with sulfa allergy.

-Max 200mg

Pharmacological TreatmentTopical NSAIDS (preferred over oral NSAIDs for pts >75 yoa)

Topical Analgesics

Drug Dosage Adverse Effects

Warnings/ Contraindications

Notes

Diclofenac sodium 1% gel (Voltaren)

->4g topically to lower extremities 4x/day->2g to upper extremities 4x/day

-Application site rxn-Burning sens. in eye-Raised IOP

-Same as NSAIDs BBWs-NSAID oral therapy not recommended concomitantly -Can cause anaphylaxis

-Max 8g/day to any single joint of upper extremity; 16g/day for lower extremity; 32g/day total over all affected joints

Trolamine salicylate 10% cream (Arthricream)

->Apply topically 3-4x/day

-Erythema-Skin irritation

-Contraindications: hypersensitivity to salicylates, severe renal insufficiency

-May cause tinnitus-Beware of toxicity with over use-Do not cover area with occlusive material

Drug Dosage Adverse Effects Warnings/ Contraindications

Notes

Capsaisin 0.025% or 0.075%

->Apply to affected joints 3-4x/day

-Application site erythema-Pruritus-Nausea-Hypertension

-May increase risk of cardiovascular adverse effects

-Use nitrile gloves for handling

Pharmacological TreatmentIntra-acrticular Glucocorticoids (knee or hip)

Drug Dosage Adverse Effects

Warnings/ Contraindications

Notes

Triamcinolone acetonide (Kenalog, Aristocrat A, Nasacort)

->initial 2.5-15mg as single injection->Additional doses can be adjusted to 20mg or more

-Cushing’s syndrome-Headache-Pharyngitis-Flu-like symptoms

-Contraindications: administration with live vaccines; idiopathic thrombocytopenic purpura

-Increased risk of infections-Impaired skin healing-Weight gain-Hyperglycemia

Triamcinolone hexacetonide (Aristospan)

->up to 0.5mg/square inch of affected skin

-Hypertension-Osteoporosis

-Same as above -Same as above-Total daily dose may vary from 2-48mg/day

Pharmacist Role

Be aware of certain labs to order for particular agents

Understand patient populations, which certain medications should be avoided in

Counsel patients on the disease state , SE, possible treatments

Assess progression of disease and appropriate measures to take

Make recommendations to physicians regarding drug regimen

Clinical Pearls- Based on Guidelines

RA Etanercept recommended

for use in patients with hepatitis C.

No biologics for hepatitis B Rituxibam recommended

for pts with malignancy <5yrs, treated skin melanoma, treated lymphoproliferative disease

TNF inhibitor recommended for patients with CHF

OA Knee

Acetaminophen Oral NSAIDs Topical NSAIDs Tramadol Intraarticular corticosteroid

injections Hip

Same as above without topical NSAIDs

Hand Topical NSAIDs Topical capsaicin Oral NSAIDs

Reference American College of Rheumatology 2012 Recommendations for the

Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee. American College of Rheumatology. vol. 64, No. 4, April 2012, pp 465–474

2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid ArthritisAmerican College of Rheumatology. vol. 64, No. 5, May 2012, pp 625–639

Kenneth C Kalunian, MD. Patient information: Osteoarthritis symptoms and diagnosis (Beyond the Basics). UpToDate August 2013.

Peter H. Schur, MD. General principles of management of rheumatoid arthritis in adults. UpToDate August 2013

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