A chronic systemic inflammatory autoimmune disease of unknown cause, involving synovial joints, resulting in joint deformities and functional limitations if not adequately controlled. The disease can also produce systemic inflammation and involve extra-articular structures and organs (e.g. skin, lungs, heart and eyes).

The precise cause is unknown. Various factors can contribute and include:

1. Environmental: Smoking induces formation of citrullinated peptides in susceptible individuals leading to formation of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factors (RF) triggering auto-immunity which underlies rheumatoid arthritis (RA)
2. Infection: Various pathogens (e.g. viruses and mycoplasma) induce inflammation and triggers autoimmunity in a susceptible host leading to RA. None of the potential pathogens appear to be RA specific, and no specific pathogen is definitely linked to RA
3. Hormonal: Female predominance, ~3 fold >males. Estrogen may play a role in RA development by facilitating immune system activation
4. Genes: Play role in susceptibility
   • May account for ~50% risk of developing RA
   • May impact disease severity
   • Class II MHC genes (containing a specific 5-amino acid sequence in the hyper variable region of HLA-DR4, called the SHARED EPITOPE), have been implicated
5. Immunologic Factors:
   • Complex process involving T and B lymphocytes, antigen presenting cells (macrophages and dendritic cells) and cytokines. The latter may have pleiotropic actions and multiple targets and may exhibit both pro-inflammatory and anti-inflammatory actions. Controlling the balance between competing cytokines is considered as an important therapeutic goal. Key pro-inflammatory cytokines are TNF, IL-1, and IL-6
   • T cells activates macrophages/synovial fibroblasts which produces proinflammatory cytokines leading to initiation of RA
   • B cells produce autoantibodies/cytokines eventually contributing to pathological injury
6. The synovial membrane is ultimately transformed into pannus tissue with activated synovial cells and osteoclasts eroding cartilage and bone

• Rheumatoid arthritis (RA) affects about 1% of the population
• Women are affected ~3 times more than men
• Onset may be at any age, most often appears between the ages of 35 and 50

Pathogenesis is not completely understood, but may include:

• Autoimmune reaction triggered by infection/trauma → synovial hypertrophy → joint inflammation (synovitis)
• Subsequent uncontrolled inflammation → cartilage and bone destruction
• Increased immune activity in genetically susceptible individuals, facilitate the disease
• Immune activity involves:
  • T cells, phagocytes, fibroblasts, osteoclasts, and neutrophils
  • B cells produce characteristic autoantibodies (i.e. rheumatoid factors [RFs] and anti-CCP)
  • Aberrant production of numerous cytokines, inflammatory mediators (e.g. TNF & IL-1), and growth factors ensues
• Inflammation, excessive proliferation of synovium, formation of granulation tissue (i.e. pannus) promotes tissue destruction

• Some experience a gradual onset, with slow progression of signs and symptoms, however many patients may present with progressive joint pain and stiffness, functional limitation and radiographic damage
• RA is also associated with significant morbidity and increased mortality, primarily related to cardiovascular disease and infections
• RA has been redefined as of 2010 by ACR/EULAR, based on the following criteria

Signs and symptoms include:

• Gradual onset, slowly progressive joint pain
• Morning stiffness ( may last 45 minutes or longer)
• Functional limitation
• Constitutional symptoms
  • Fatigue/malaise
  • Anorexia
  • Generalized weakness
  • Low grade fever
• Boutonniere deformity: PIP joint is flexed and DIP joint hyperextended
• Swan-neck deformity: DIP joint is flexed and the PIP joint is hyperextended
• Baker’s cyst: The synovial sac of knee joint produces a bulge into the popliteal space and forms a cystic swelling, which can rupture and cause pain

Extra-articular manifestations:

• Less common with better therapy
• Subcutaneous rheumatoid nodules at sites of pressure and chronic irritation
• Damage to the ligaments and tendons
• Vasculitis causing leg ulcers
• Lymphadenopathy
• Felty’s syndrome (splenomegaly and leukopenia)
• Sjögren’s syndrome (dry eyes, mouth, skin etc.)
• Scleromalacia
• Episcleritis
• Involvement of the cervical spine can cause atlantoaxial subluxation and spinal cord compression
• Cardiac: Pericarditis, valvular disease, pericardial effusion (usually asymptomatic)
• Lung: Pleural effusion with very low glucose level, pulmonary nodules, infiltrates and fibrosis
• Blood: Anemia with normal MCV
• Nerve: Mononeuritis multiplex
• Skin: Nodules at pressure points

History:

Detailed history should include:

• History of joint pain
  • Duration
  • Number of Joints involved
  • Frequency
• History of stiffness/swelling over the joints
• History of constitutional symptoms e.g. fatigue, malaise, weakness
• Inquiries about quality of life
• Inquiries if disease interferes with daily activities
• Family history of RA

Physical Examination:

Is required for assessment of joint inflammation and structural deformity, by the clients care giver and should include:

• Assessment of symmetric joint swelling is characteristic of RA
• Palpation of joint can distinguishes swelling from bony enlargement
• Pain occurring with both active and passive movement is a hallmark of joint inflammation should be reported
• Persistent inflammation of tendons and muscles of the joints

Laboratory Tests:

The presence of prognostic features should be assessed at baseline and considered when making treatment decisions; they are also used to monitor the disease activity and medication effects:

Pretreatment or baseline investigations include:

• CBC, LFTs, urea, creatinine
• ESR-usually elevated as is CRP paralleling the disease activity
• CRP (C reactive protein)
• RF (rheumatoid factor); an immunoglobulin antibody
  • Present in ~75% of patient
  • Reflects disease activity to some extent, but not usually measured serially
• ANTI-CCP (anti-cyclic citrullinated peptide antibodies): Highly specific in early disease

Screening before starting biologic therapy:

• Hepatitis B and C (and HIV in high-risk patients)
• Screening for latent tuberculosis is recommended prior to anti-TNF, abatacept, and tocilizumab
• Baseline antinuclear antibody (ANA) may be considered

Imaging:

X-rays:

• First choice for screening of affected joints
• Images of hands/feet may be done as frequently as every 6-12 months in patients with recent-onset disease, and at longer intervals in those with established disease

MRI:

• May provide more detail of erosions, synovitis and bone edema, but is expensive and not widely available

Ultrasound:

• May help in visualizing effusions, erosions and synovitis by Grey scale and power Doppler assessments
• Helpful in assessing some joints (e.g. hip joints) in obese patients

Bone scan:

• Radionuclide scans distinguish between inflammatory and non-inflammatory processes
• Bone Densitometry (DEXA) provides info regarding osteoporosis

Diagnostic procedures:

Arthrocentesis:

• Needed to diagnose superimposed septic arthritis
• Considered if one joint is inflamed out of proportion to other joints.

Findings consistent with RA are:

• Yellowish-white fluid, turbid, poor viscosity
• WBC increased (3,500-50,000)
• Negative for crystals and on culture

Diagnostic criteria:

• Early intervention improves disease outcome and decreases joint damage
• The criteria are aimed at assessing those with clinical synovitis or with synovitis not explained by any other cause. The number and types of joints (large and/or small) involved, serology for (rheumatoid factor) RF and/or (anti-citrullinated protein antibody) ACPA, acute phase reactants (CRP and ESR) and duration of symptoms are all taken into account when making the diagnosis of RA. Patients presenting with new symptoms as well as those with existing erosive disease should be reassessed to determine if they fulfill the 2010 criteria for RA
• RA has been redefined as of 2010 by ACR/EULAR, based on the following criteria

Goal: Satisfactory treatment for RA should achieve the following

• Relief of signs and symptoms (i.e. joint swelling and tenderness)
• Improvement of physical functioning and quality of life
• Inhibition of the progression of joint damage
• Minimal loss of functional ability of the affected joints
• Participate in planning and carrying out the therapeutic regimen
• Maintain a positive self-image

Treatment:

• Pharmacological interventions
• Non-pharmacological interventions
• Surgical interventions

PHARMACOLOGICAL INTERVENTIONS:

• Patients are symptomatically treated as they present to the clinic. Previously undiagnosed patients with possible RA diagnosis should be given an urgent referral to the rheumatologist for definitive diagnosis and treatment
• Treatment approach has undergone major changes over the years:
  • NSAIDs are beneficial only for relief of symptoms
  • NSAIDs have no effect on disease retardation
  • Irreversible joint damage may occur in early disease

1. NSAIDs:

• Recommended for the relief of symptomatic pain and inflammation (if present)
• No longer used as the sole first-line agent for RA

2. Disease modifying antirheumatic drugs (DMARDs):

Start DMARDs immediately if patient has active disease.

• Active RA require frequent monitoring (every 1-3months)
• Patients with well controlled disease may be monitored less frequently
• DMARD therapy should be adjusted every 3-6 months, to achieve treatment goals

Ref: Bykerk V P et al. J Rheumatol 2011; 38:11.

Types of DMARDs:

• Nonbiologic
• Biologic

A. Nonbiologic DMARDs:

Includes and are usually chosen to initiate therapy, due to fast onset of action and less toxicity

• Methotrexate (MTX): Most preferred of all the DMARDs
  • 7.5-25 mg per week PO, plus folic acid 5mg PO daily to prevent from toxicity
  • Although unlabeled route; SC route may be more effective and better tolerated, especially at doses greater than 15 mg/week. Dose should be escalated quickly to at least 15-20 mg/week in most patient
  • Monitor CBC, renal, and liver function every 8-12 weeks
  • Contraindicated in renal disease
  • Most patients treated with MTX exhibit clinical and radiological improvement, a change in therapy should be considered in patients with radiographic progression despite adequate clinical response
• Sulfasalazine: 500 mg/day; max: 2-3 g/day; 3-month trial. Monitor CBC, liver enzymes every 8-12 weeks. Screen for G6PD deficiency
• Hydroxychloroquine: Dose is based on body weight not to exceed 400 mg/day; or 6.5mg/kg/day in general. Used in milder forms or in combination with other DMARDs. Yearly ophthalmologic exam. Adjust dose in renal insufficiency
• Minocycline /Cyclosporin/Azathioprine: Can be considered as alternative options
• Leflunomide: 10-20 mg/day. Modifies T-cell function to decrease autoimmune activity and reduce structural damage. Side effects: GI disturbances, hair loss, hypertension, liver and lung toxicity; also potentially teratogenic
• Intramuscular gold /D-penicillamine: Rarely induce sustained remission. Have been largely replaced by more effective agents

Note: Glucocorticoids may be used for flare-ups while initiating or waiting for DMARDs to take affect. Lowest possible effective dose for short time period is suggested.

• Prednisone: 5-10 mg/day is commonly used in patients to bridge the therapy in early RA. Once the disease is controlled; it should be weaned to the lowest possible dose, and then stopped to avoid adverse effects of steroid use
• Combination therapy with DMARDs indicated if:
  • Poor prognostic features
  • Moderate to high disease activity
  • Inadequate response to monotherapy
• Note: MTX is used as an anchor agent unless contraindicated

B. Biologic DMARDs:

• Switch to biological agents if:
  • At least 2 nonbiologic DMARDs (including MTX), have failed to control disease activity with mono or combination therapy after 3 months of targeted dose
• Approved agents include:
  • Tumor necrosis factor inhibitors
    • Infliximab
    • Adalimumab
    • Etanercept
    • Golimumab
    • Certolizumab pegol
  • T cell costimulatory inhibitors
    • Abatacept (ABAT)
  • B lymphocyte depleting agent
    • Rituximab (RTX)
  • Interleukin 6 (IL-6) antagonist
    • Tocilizumab (TCZ)
  • IL-1receptor antagonist
    • Anakinra
  • No evidence to suggest that one is superior to the other, though anakinra appears to be least effective agent, except for Adult Still’s disease variant of RA. Combination with MTX appears to be the most effective regimen for most biologics
  • If a patient achieves sustained remission after discontinuation of NSAID and glucocorticoids, a reduction in traditional and biologic DMARD can be attempted

NON-PHARMACOLOGICAL INTERVENTIONS:

Supportive measures

• Nutrition
• Rest
• Physical measures
  • Joint splinting
  • Orthopedic or athletic shoes
  • Exercises
  • Heat and cold therapy
  • Paraffin baths
  • Massage

Surgical Interventions:

• Tendon reconstruction, joint fusion, and joint replacement are potential treatment modalities to prevent disability in advanced RA

Nursing Management:

• Assess/Identify patient’s issues and concerns due to the diagnosis of RA
• Chronic nature of the illness may result in disability, patient are anxious and require continuous reassurance and assistance to cope up with the illness
• Address following issues:
  • Pain and fatigue
  • Altered moods and sleep disturbances
  • Limited mobility
• In young women, discuss and develop strategies addressing:
  • Concerns due to childbearing potential
  • Taking care of the family along with work responsibilities
• RA has no cure, help patient to accept it, and provide help and support to improve quality of life
• Assist and teach techniques to cope up with pain, and mobility
• Educate patients about the use of alternative or complementary therapies, and always advise to discuss these therapies with their caregivers and physicians. Some of the common agents are discussed below

Complementary and alternative therapies:

• Boswellia:
  • Anti inflammatory and analgesic effect
  • Dose: 150 mg PO TID for 2-3 months
  • Adverse effect: Generally safe
• Ginger:
  • Anti-inflammatory and analgesic effect
  • Dose: 1 tsp freshly grated in a cup of hot water as tea
  • Adverse effect: large doses may cause GI disturbances, and may cause bleeding if given with anticoagulants
• Turmeric (Curcumin):
  • Decrease prostaglandin production and increase cortisol to reduce inflammation
  • Dose: 400 mg PO TID
  • Adverse effect: High dose and prolong use may cause stomach ulcers
• Cayenne Pepper (Capsicum):
  • Thought to deplete substance P, reducing pain transmission
  • Dose: Applied topically to skin over joints in concentrations of 0.025-0.25%
  • Adverse effect: Takes several days to obtain pain relief; do not use with heat application
• Stinging Nettle:
  • Boosts effect of nonsteroidal anti-inflammatory drugs
  • Dose: 1-2 tsp dried leaves in 1 cup boiling water twice daily; 150-300 mg capsule daily
  • Adverse effect: Allergic reaction may occur
• Kava:
  • Muscle relaxant and antianxiety
  • Dose: 70-240 mg kava pyrone daily
  • Adverse effects: May cause change in motor response and judgment; do not mix with central nervous system depressants
• Glucosamine and Chondroitin:
  • Cartilage repair
  • Dose:
    • Glucosamine: 1,000-2,000 mg daily
    • Chondroitin: 800-1,600 mg daily, based on weight
  • Adverse effects: Bleeding risk if aspirin (ASA) taken with chondroitin; may be effective either alone or as combination; must be taken for several months to achieve noticeable effect

Follow-up Recommendations

• Monitor patient regularly.
• Address risk factors and evaluate for osteoporosis, a major comorbidity that can result from the disease itself or corticosteroid use
• For patients at risk for cardiovascular disease use low dose aspirin prophylaxis as required
• Educate patient, provide information about accessible resources

Prognosis

• Poor prognostic findings:
  • Persistent moderate to severe disease
  • Inheritance of shared epitope
  • Early or advanced age at disease onset
• 50% cannot function in primary job within 10 years of onset

NSAIDs-Analgesic

TYPES

• Salicylates
• Acetic acid derivatives
  • Diclofenac
  • Etodolac
  • Indomethacin
  • Sulindac
• Enolic acid (Oxicam) derivatives
  • Meloxicam
  • Piroxicam
  • Tenoxicam
• Napthylkanone derivatives
  • Nabumetone
• Propionic acid derivatives (profens)
  • Fenoprofen
  • Flurbiprofen
  • Ibuprofen
  • Ketoprofen
  • Naproxen
  • Oxaprozin
• COX-2 inhibitors
  • Celecoxib

NSAIDs Mechanism(s):

• Prostaglandins are common locally produced chemicals mediating pain, fever, and inflammation
• These drugs reversibly inhibit cyclooxygenase-1 and 2 (COX-1 and 2) enzymes
• This results in decreased formation of prostaglandin precursors

Acetylsalicylic acid: (additional MODE OF ACTION)

• Irreversibly interferes with the production of thromboxane A₂ within the platelet, thus inhibiting platelet aggregation

NSAIDs Doses:

Salicylates: (rarely used for RA therapy at present)

Aspirin

• 325-650 mg PO daily, every 4-6 hrs; Max. 4 g/day

Diflunisal

• 500-1000 mg/day PO in 2 divided doses

Renal impairment:

• Cl_Cr<50 mL/minute: Decrease by 50% of normal dose

Acetic Acid Derivatives:

Diclofenac

• Immediate-release: 50 mg PO BID or TID; Max. 150 mg/day
• Slow-release: 75-100 mg PO once a day; Max. 150 mg/day
• Rectal suppository: 50-100 mg/day; Max. 100 mg/day or combined dose(rectal+oral) is 150 mg/day

Diclofenac/Misoprostol

• 50 mg/200 mcg and 75 mg/200 mcg tablets; Max. 150 mg Diclofenac/day

Etodolac

• Immediate-release: 200-300 mg PO BID or TID; Max. 1000 mg/day

Indomethacin

• 25-50 mg PO BID or TID; Max. 200 mg/day
• Extended-release: 75 mg PO BID or TID; Max. 150 mg/day

Sulindac

• 150-200 mg PO BID; Max.400 mg/day

Enolic Acid (Oxicam) Derivatives:

Meloxicam

• 7.5 mg PO once daily; may increase to 15 mg daily; Max. 15 mg/day

Piroxicam

• 10-20 mg PO once daily; Max. 20 mg/day

Tenoxicam

• 10-20 mg PO once daily; usual dose 20 mg PO once daily

Napthylkanone Derivative:

Nabumetone

• 1000 mg PO once daily; may increase upto 2000 mg/day in 2 divided doses

Renal impairment:

• ClCr 30-49 mL/minute: 750 mg/day may increase upto 1500 mg/day

Propionic Acid Derivatives (profens):

Fenoprofen

• 300-600 mg PO TID or QID; Max. 3.2 g/day

Flurbiprofen

• 200-300 mg PO daily in 2,3 or 4 divided doses Note: Do not administer more than 100 mg per single dose; Max 300 mg/day

Ibuprofen

• 200-800 mg PO TID or QID; Max. 3.2 g/day

Ketoprofen

• Regular release: 150-200 mg PO TID or QID; Max. 300 mg/day
• Extended release: 200 mg PO daily
• Renal impairment:
• Mild: 150 mg/day
• Severe (Clcr <25mL/min): 100 mg/day

Naproxen

• Regular release: 250-500 mg PO BID; may increase to 1.5 g/day
• Extended release: 750-1000 mg PO BID or once daily
• EC-Naproxen + IR-Esomeprazole: 375/20 mg or 500/20 mg PO BID

Oxaprozin

• 600-1200 mg PO daily; Max. 1800 mg or 26 mg/kg, whichever is less

COX-2 inhibitors:

Celecoxib

• Initial 100 mg PO BID may increase to 200 mg/day PO BID; Max. 200 mg/day

Analgesic, Non-NSAID

• Acetaminophen

Mechanism:

• Analgesic action: Inhibits the synthesis of prostaglandins in the central nervous system
• Antipyretic action: Inhibits the hypothalamic heat-regulating center

Dose:

Acetaminophen

• 325-650 mg PO every 4-6 hrs or 1000 mg PO TID or BID; Max. of 4 g/day and 1 gm/dose

Corticosteroid

• Betamethasone
• Methylprednisolone acetate (most commonly used)
• Triamcinolone acetonide
• Triamcinolone hexacetonide

Mechanism:

• Decreases inflammation and the normal immune response through multiple mechanisms, also suppresses adrenal function at high dose, also has mineralocorticoid activity.

Doses:

Betamethasone (Intra-articular):

• Hip: 1-2 ml
• Knee, ankle, shoulder: 1 ml
• Elbow, wrist: 0.5-1 ml
• Metacarpophalangeal, sternoclavicular: 0.25-0.5 ml

Methylprednisolone (Intra-articular):

• Ankle, shoulder: 40 mg dose
• Hip: 80-160 mg
• Knee: 40-80 mg
• Elbow, wrist: 20-40 mg
• Small joint like MCP, PIP, DIP, SC joint: 10 mg

Triamcinolone acetonide (Intra-articular):

• Large joints: 5-40 mg
• Small joints: 2.5-10 mg

Triamcinolone hexacetonide (Intra-articular):

• Large joints: 10-20 mg
• Small joints: 2-6 mg

NONBIOLOGIC DMARDs

Antimetabolite/Antirheumatic Agent

• Methotrexate

Mechanism:

• It is a folate antagonist that inhibits DNA synthesis and cell reproduction
• Inhibits purine and thymidylic acid synthesis
• It also has immune modulator and anti-inflammatory actions

Dose:

Methotrexate

• Oral: Initiate at 7.5-15 mg/week PO given as a single dose or divided in 3 equal doses at 12 hour intervals for 3 doses along with folic acid; Max. 25 mg/week
• Subcutaneous: 7.5-25 mg once weekly

Anti-inflammatory (5-Aminosalicylic Acid Derivative)

• Sulfasalazine

Mechanism:

• Actual mechanism not determined
• Interferes with secretion by prostaglandin synthesis inhibition

Dose:

Sulfasalazine

Slow release formulation prescribed as follows:

• Week 1 = 500 g/day PO at bed time daily
• Week 2 = 500 g/day PO BID
• Week 3 = 500 g/day PO in the morning and 1000 g PO at bedtime
• Week 4 and onwards: 1000 g/day PO BID
• Note: May increase to maximum 3 g/day, if response to 2 g/day is inadequate after 2 months of use

Antirheumatic Agent, Gold Compound

• Sodium Aurothiomalate (rarely used in current management of RA)

Mechanism:

• Unknown, may decrease prostaglandin synthesis or may alter cellular mechanisms by inhibiting sulfhydryl systems
• It exhibits anti-inflammatory, antiarthritic and immunomodulating effects

Dose:

Sodium Aurothiomalate

• Intramuscular Injections: 1st week: 10 mg IM, 2^nd week: 25 mg IM, then 25 to 50 mg IM weekly for the next 20 weeks or until toxicity occur
• Maintenance: 50 mg IM tapered progressively to every 2 to 4 weeks according to clinical response and tolerance, and maintained indefinitely

Antirheumatic-Immunomodulator Agent

• Leflunomide

Mechanism:

• Inhibits pyrimidine synthesis via dihydroorotate dehydrogenase, resulting in antiproliferative and anti-inflammatory effects

Dose:

Leflunomide

• 20 mg PO daily; may decrease dose to 10 mg PO daily if 20 mg PO is not tolerated well

Anti-inflammatory-Antimalarial

• Hydroxychloroquine

Mechanism:

• Exact mode of action in controlling these diseases is unknown
• Antirheumatic/immunosuppressive effects: Inhibits rheumatoid factor, acute phase reactants, and many enzymes

Dose:

Hydroxychloroquine (rarely used now)

• Start 200-400 mg/day PO; do not exceed 6.5 mg/kg dose
• Note: Eye checkups for retinal toxicity required on an annual basis

Immunosuppressant Agent

• Azathioprine

Mechanism:

• Complete mechanism of immunosuppression is not fully known
• It antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins
• May also interfere with cellular metabolism and inhibit mitosis

Dose:

Azathioprine

• Start 1 mg/kg/day PO daily or in 2 divided doses for 6-8 weeks; may increase by 0.5 mg/kg every 4 weeks, up to 2.5 mg/kg/day; for minimum of 12 weeks
• Maintenance dose: Reduce dose by 0.5 mg/kg (~25 mg daily) every 4 weeks until lowest effective dose is reached

BIOLOGIC DMARDs

Tumor necrosis factor (TNF) Inhibitors

• Infliximab
• Adalimumab
• Etanercept
• Certolizumab pegol
• Golimumab

Mechanism:

• Neutralizes the biological activity of TNFα by
  • Binding with high affinity to the soluble and transmembrane forms of TNFα
  • Inhibits binding of TNFα with its receptors
• Leads to an overall reduction in inflammation

Note: Etanercept also neutralize TNFβ (lymphotoxin α)

Dose:

Infliximab

• In combination with methotrexate: 3 mg/kg IV at 0, 2, and 6 weeks, then 3 mg/kg IV every 8 weeks thereafter; may increase dose to 10 mg/kg or decrease dosing interval to as often as every 4 weeks if needed

Adalimumab

• 40 g SC every other week; may increase dose to 40 mg SC every week

Etanercept

• 50 mg SC once weekly; may be given as 25 mg SC twice weekly (individual doses should be at 3 or 4 days apart)

Certolizumab pegol

• 400 mg SC at 0, 2 and 4 weeks; then 200 mg every other week; may consider maintenance dose of 400 mg every 4 weeks

Golimumab

• In combination with methotrexate: 50 mg SC once per month

Antirheumatic, Disease Modifying; Interleukin-1 Receptor Antagonist

• Anakinra (used only for adult Still’s disease variant of RA)

Mechanism:

• Antagonist of the interleukin-1 (IL-1) receptor
• Endogenous IL-1 is induced by inflammatory stimuli and mediates a variety of immunological responses, including degradation of cartilage (loss of proteoglycans) and stimulation of bone resorption

Dose:

Anakinra

• 100 mg SC once daily. Administer at approximately the same time each day

Renal impairment

• ClCr <30 mL/min or End Stage Renal Disease: 100 mg SC every other day

Antirheumatic, Disease Modifying; Interleukin-6 Receptor Antagonist

• Tocilizumab

Mechanism:

• Antagonist of the interleukin-6 (IL-6) receptor
• Endogenous IL-6 is induced by inflammatory stimuli and mediates a variety of immunological responses
• Inhibition of IL-6 leads to a reduction in cytokine and acute phase reactant production

Dose:

Tocilizumab

• 4 mg/kg IV infusion over 1 hour every 4 weeks; may be increased to 8 mg/kg based on clinical response. Maximum 800 mg/infusion

Antirheumatic, Disease Modifying; Selective T-Cell Costimulation Blocker

• Abatacept

Mechanism:

• Selective costimulation modulator
• Inhibits T-cell (T-lymphocyte) activation by binding to CD80 and CD86 on antigen presenting cells (APC), thus blocking the required CD28 interaction between APCs and T cells

Dose:

Abatacept

Note: Administered as a 30-minute intravenous infusion utilizing weight based dosing and following the initial IV infusion, repeat IV dose (using the same weight-based dosing) at 2 weeks and 4 weeks after the initial infusion, and every 4 weeks thereafter.

• Weight
• <60 kg: 500 mg
• 60-100 kg: 750 mg
• >100 kg: 1000 mg

Biologic-Selective B cell Depleter

• Rituximab

Mechanism:

• Binds specifically to the antigen CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35) on the cell surface
• Activate complement-dependent B-cell cytotoxicity; and to human Fc receptors, mediating cell killing through an antibody-dependent cellular toxicity

Dose:

Rituximab (IV infusion)

• Initial 1000 mg followed two weeks later by the second 1000 dose; subsequent courses may be administered every 24 weeks (based on clinical evaluation), if necessary may be repeated no sooner than 16 weeks following the previous course

Note: Infusions should be administered in a setting where full resuscitation facilities are available, and under the close supervision. Also administer 100 mg IV methylprednisolone 30 minutes prior to both Rituximab infusions. Acetaminophen and diphenhydramine may also be given prior to rituximab.

Diagnosis:

• Acute and chronic pain related to inflammation
• Fatigue related to disease activity
• Impaired mobility due to
  • Pain
  • Decreased range of motion
  • Improper or no use of ambulatory devices
• Physical and psychological changes
• Dependency imposed by the illness
• Self care deficits related to contractures
• Recognize ineffective coping due to life style changes
• Recognize complications secondary to medications
• Disturbed body image related to change in body structure and function

Goals:

• Improve pain and comfort level by
  • Controlling pain
  • Reducing inflammation
  • Prevention or correcting of joint deformity
• Develop strategies in daily activities to minimize fatigue
• Achieves and maintain functional mobility
• Adapts to the physical and psychological limitations
• Achieve self care independently
• Educate to manage complications due to medication
• Minimal loss of functional ability of the affected joints
• Participate in planning and carrying out the therapeutic regimen
• Maintain a positive self-image

Employ a comprehensive program to meet goals

• Drug therapy
• Rest
• Joint protection
• Heat and cold applications
• Exercise
• Client and family teaching

Controlling pain and relieving discomfort:

• Pain relief – Can be achieved by joint protection, exercise, relaxation and thermal modalities as follows:
  • Application of local heat or cold to the affected joints for 15 to 20 minutes 4 times a day. Caution in patients with impaired sensations
  • Rest, massage, change of positions
  • Change in mattress, supportive pillows and splints
  • Activities to relax and at the same time divert attention from pain
  • Weight reduction programme may be advised to release stress over joints
  • Help client find ways to modify daily activities
• Pain relief – analgesic use
  • Treatment is largely individualized, and compliance is important
• Administer or teach self-administration of medications
  • Teach patient when to expect pain relief, based on the action of the drug
• Encourage patients to be vocal about pain and chronicity of the disease, which allow for adequate medication use, better pain control, and development of different coping strategies
• Identifying factors which exacerbate and influence the pain response
• Assess subjective changes and manage them

Decreasing fatigue:

• Fatigue can be acute or chronic
  • Acute fatigue is usually for a brief period and is relieved by rest or sleep
  • Chronic fatigue is persistent, accumulative and not usually relieved by rest; corresponds to disease activity
    • Factors attributing to chronic fatigue are as follows:
    • Persistent pain
    • Sleep disturbances
    • Impaired physical activity
    • Disease duration
  • All the above require additional physical and emotional energy
• Energy is regained to reduce chronic fatigue as follows:
  • By having appropriate amount of rest periods
  • Alternate rest with activity throughout the day
  • Rest before becoming exhausted
  • Splints and assistive devices provide rest and protection to the joints during activity
  • Relaxation techniques helps in reducing stress
  • Improvement in functional status improve mood and help depression
  • Planning and dividing activities in groups, may help patient to minimize some activities e.g. climbing stairs
  • Promoting sleep to help reduce fatigue
  • Provide quite dark environment to encourage restful sleep
  • Have a set (routine) time to go to bed

Increasing Mobility: To prevent inflammation and deformities it is important to position and support all joints correctly

• Encourage a warm bath or shower in the morning to decrease morning stiffness
• Encourage measures to protect affected joints
  • Perform gentle ROM exercises
  • Use splints
  • Assist with ADLs if necessary
• Encourage exercise consistent with degree of disease activity
• Refer to physical therapy and occupational therapy, as required

Facilitating self care:

• Self care deficits due to fatigue, contractures, and loss of mobility, are overcome by using adaptive devices to keep patient independent
• By relieving pain, stiffness and fatigue, patient’s ability to self care is increased
• Help client find ways to modify daily activities

Strengthening the coping skills and improving the body image:

• All aspects of life are altered, due to unpredictable course of RA and include:
  • Self perception
  • Social life
  • Sexual functions
  • Work responsibilities
  • Family care
  • Financial status
• Body image changes are main reason for social isolation and depression. Referrals to social worker or mental health counselor may be considered
• The nurse should help patient and family to identify and verbalize all issues individually
  • Strengthen areas which has some control over disease symptoms and treatment
  • Reinforce effective coping mechanisms/skills
  • Advise to comply with the treatment plan, for better outcome

Monitoring and managing potential complications:

• Avoiding medication induced complication by:
  • Monitoring adverse effects periodically (labs and physical assessment)
  • Nurse should help patient be aware of and recognize potential side effects, e.g.
    • Bone marrow suppression
    • GI bleeding
    • Kidney or liver toxicity
    • Oral ulcers/rashes
    • Changes in vision
• Educate patient to promptly report side effects to the caregiver
• Patient may have increase in symptoms while introducing a new agent, nurse counseling is important in such times

Patient Education:

• Patient and family should have an understanding of the nature of disease
  • Characteristic exacerbations and remissions with time
  • Systemic affects; involvement of other organ
  • Variable severity, but most patients are not confined to bed or wheelchair
• Educate about pharmacologic agents
  • Compliance and consistency is the key to maximum benefit
  • Most medications require labs to monitor for potential side effects
  • Prompt reporting of adverse effects
  • Advise patients to discuss the use of any complementary or alternative therapies
  • Reinforce to patient the need for lifelong treatment
• During periods of remission, encourage patient to exercise regularly such as:
  • Dancing
  • Walking
  • Stationary bicycle in the home
  • Join local community centre, gyms, YMCA etc.; ask about special programs for arthritis
• For additional information and support, refer to the Arthritis Foundation (www.arthritis.org)

Expected Outcomes:

• Reports reduction in pain
• Wears wrist splints correctly and performs ROM exercises twice per day
• Maintains independence for toileting, bathing, and feeding
• Verbalizes/shares concerns about cleaning and cooking; meets with occupational therapist

• Be aware of loss of joint function because of bony adhesions and damage of supporting structures
• Treatment for RA has potential complications, if not monitored closely

Core Resources:

• Aletaha D, Neogi T, Silman AJ et al.2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis & Rheumatism 2010, 69; 1580-1588
• Bykerk V P, Akhavan P, Hazelwood GS, et al. Canadian Rheumatology Association Recommendations for Pharmacological Management of Rheumatoid Arthritis with Traditional and Biologic Disease-modifying Antirheumatic Drugs. J Rheumatol 2011; 38:11; doi:10.3899/jrheum.110207
• Compendium of Pharmaceuticals and Specialties (CPS). Canadian Pharmacist association. Toronto: Webcom Inc. 2012
• Day RA, Paul P, Williams B, et al (eds). Brunner & Suddarth’s Textbook of Canadian Medical-Surgical Nursing. 2^nd ed. Philadelphia: Lippincott Williams and Wilkins; 2010
• Dirksen, S., Lewis, S., & Collier, I., Heitkemper, M., O’Brien, P., & Bucher, L. (2010). Medical-Surgical Nursing in Canada: Assessment and management of clinical problems (2^nd ed.). Toronto: Mosby Elsevier
• Foster C, Mistry NF, Peddi PF, Sharma S, eds. The Washington Manual of Medical Therapeutics. 33^rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010
• Gray J, ed. Therapeutic Choices. Canadian Pharmacists Association. 6^th ed. Toronto: Webcom Inc. 2011
• Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 11^th ed. New York: McGraw-Hill; 2009
• Longo D, Fauci A, Kasper D, et al (eds). Harrison’s Principles of Internal Medicine. 18^th ed. New York: McGraw-Hill; 2011
• McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis & Treatment. 49^th ed. New York: McGraw-Hill; 2010
• Moskowitz RW, Altman RD, Hochberg MC et al. (2007). Osteoarthritis: Diagnosis and medical/surgical management.(4^th ed) Philadelphia:Lippincot Williams and Wilkins
• Pagana KD, Pagana TJ eds. Mosby’s Diagnostic and Laboratory Test Reference. 9^th ed. St. Louis: Elsevier-Mosby; 2009
• Skidmore-Roth L. ed. Mosby’s drug guide for nurses. 9^th ed. St. Louis: Elsevier-Mosby; 2011
• Skidmore-Roth L, ed. Mosby’s nursing drug reference. 24^th ed. St. Louis: Elsevier-Mosby; 2011
• Online resource/weblinks:
  • The Merck Manuals
  • RheumInfo
  • The Arthritis Society, Canada
  • Canadian Agency for Drugs and Technologies in Health

Online Pharmacological Resources:

• e-therapeutics
• Lexicomp
• Rxlist
• Epocrates Online

Journals/Clinical Trials:

• Breedveld FC, Weisman MH, Kavanaugh AF et al. A Multicenter, Randomized, Double-Blind Clinical Trial of Combination Therapy With Adalimumab Plus Methotrexate Versus Methotrexate Alone or Adalimumab Alone in Patients With Early, Aggressive Rheumatoid Arthritis Who Had Not Had Previous Methotrexate Treatment(PREMIER) Arthritis & Rheumatism Vol. 54, No. 1, January 2006, pp 26-37
• Grigor C; Capell H; Stirling A; et al. Effect of a treatment strategy of tight control for rheumatoid arthritis- the TICORA Study. The Lancet; Jul 17-Jul 23, 2004; 364, 9430
• Issues in Emerging Health Technologies: Rituximab for Rheumatoid Arthritis. Retrieved from Canadian Agency for Drugs and Technologies in Health. 2006; 89 www.cadth.ca
• Klarenbeek NB, Güler-Yüksel M, van der Kooij SM et al. The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis. 2011 Jun; 70(6):1039-46
• Klareskog L; Heijde DVD; P de Jager J; Gough A; et al. Therapeutic effect of the combination of etanercept and MTX compared with each treatment alone in patient with rheumatoid arthritis(TEMPO) The Lancet; Feb 28, 2004; 363, 9410
• Lipsky PE, Desiree, Heijde VD et al. Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis (ATTRACT). N Engl J Med 2000;343: 1594-602
• Moreland, L W., O’Dell,J R., et al. Treatment of Early Aggressive RA: A Randomized, Double-Blind, 2-Year Trial Comparing Immediate Triple DMARD Versus MTX Plus Etanercept to Step-up From Initial MTX Monotherapy(TEAR). Arthritis & Rheumatism, Volume 60, October 2009 Abstract Supplement.10:1895. DOI: 10.1002/art.26968
• Rantalaiho V, Korpela M, Laasonen L, et al. Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial(FINRACO) Arthritis Research & Therapy 2010, 12:R122
• http://arthritis-research.com/content/12/3/R122
• R F van Vollenhoven, S Ernestam, P Geborek et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial.Lancet 2009; 374: 459-66
• Schnitzer TJ, Hochberg MC, Marrero CE et al. 2011, 285-297