Treatment

• To achieve clinical & radiological remission of disease
  • Low disease activity is a treatment goal alternative in long standing disease
• To reduce functional limitations & permanent joint damage

• It is recommended that early treatment w/ DMARDs is initiated to control the signs & symptoms of RA & to limit radiographic damage
• Treatment depends upon time of diagnosis, disease activity, prognostic factors & response to therapy
• Treatment should be adjusted at least every 3 mth w/ strict monitoring
• Treatment target is almost reached w/in 3 mth & may be attained by the end of 6 mth
  • During 3-6 mth period, meticulous follow-up should be done & existing treatment should be intensified or changed for another
• If the treatment target has not been achieved w/ the 1st DMARD strategy, in the absence of poor prognostic factors, switching to another non-biological DMARD should be considered
  • If poor prognostic factors are present, addition of a biological DMARD may be considered
• DMARD treatment should be started upon diagnosis of RA
  • Baseline studies should be obtained prior to initiation of treatment
• Methotrexate should be part of the 1st treatment strategy in patients w/ early & established RA
• In DMARD naive patients, non-biological DMARD monotherapy & combination therapy should be considered
• As initial short-term treatment, addition of corticosteroids to either monotherapy or combination therapy w/ DMARDs has been shown to provide benefits

• Clinically important as some authorities base the treatment on disease severity
• RA can be characterized as mild, moderate or severe which is best applied to untreated patients

• Patients meet the criteria for RA, have <6 inflamed joints, w/ absence of extra-articular involvement & evidence of bone erosions or cartilage loss on X-ray

• Patients have 6-10 inflamed joints
• Presence of some of the ff: elevated ESR &/or CRP, positive RF &/or ACPA, appearance of inflammation as well as minimal joint space narrowing & small peripheral erosions on X-ray, absence of extra-articular disease

• Patients have >20 inflamed joints, elevated ESR &/or CRP
• Presence of ≥1 of the ff clinical features: anemia of chronic disease &/or hypoalbuminemia, positive RF &/or ACPA, appearance of bone erosions & cartilage loss on X-ray, presence of extra-articular disease

• In persistent remission of at least 12 mth, biological DMARDs should be slowly tapered by expanding the interval between doses or dose reduction, while continuing non-biological DMARDs
• Ceasing treatment w/ non-biological DMARDs is associated w/ increased flare frequency, hence tapering should be done cautiously & should be evaluated rigorously

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Non-Pharmacological Therapy

• Educate the patient about the nature of the disease, risks of joint damage & loss of function
• Emphasize the benefits & risks of the existing treatment modalities

• Has been shown to increase muscle strength, improve muscle function & joint stability, increase aerobic capacity & physical performance
• Can improve the overall pain control & quality of life w/o increase in disease activity
• Range of motion exercises help restore or preserve joint motion
• Exercise programs should be tailored based on patient’s disease severity, body build & previous activity level

• Aimed to provide pain relief, reduction of inflammation & preservation of joint integrity & function
• Involves passive & active exercises to improve & maintain the range of motion of joints, heat or cold application & relaxation techniques
• Podiatry referral should be offered to all patients

• Helps patients maximize physical function & improve their level of independence
• Focus of therapy is on upper extremity activities
• May involve education on joint protection & self care, & instruction on the use of assistive devices

• Encourage obese patients to lose wt
• Food rich in fish oil or eicosapentaenoic acid or docosahexaenoic acid may provide decrease in symptoms

• Resting & working splints have been shown to provide pain relief, increase joint stability & improve function

• Influenza & pneumococcal vaccines should be administered to all RA patients who are going to be or are already treated w/ immunosuppressive medications
• Should give Hepatitis B vaccine prior to treatment w/ Methotrexate, Leflunomide & all biologic DMARDs

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Pharmacological Therapy

• Have the potential to reduce or prevent radiographic progression, improve joint function, maintain joint integrity, & improve the signs & symptoms of RA
• Choice of initial DMARD should be based on patient’s preferences & existing comorbidities
• There is no strong evidence that there is a difference in efficacy or safety among Methotrexate, Leflunomide or Sulfasalazine
• Methotrexate & Leflunomide are preferred to Sulfasalazine in patients w/ high disease activity

• Recommended as part of the initial treatment strategy in patients w/ contraindication to or intolerance of Methotrexate
• Adverse Reactions:
  • Dermatologic effects (rash, pruritus, lesions on the mucous membrane); GI effects (persistent diarrhea, ulcerative colitis, stomatitis, anorexia); Hematologic effects (anemia, agranulocytosis); Other effects (alopecia, elevated LFT, hematuria, proteinuria)
• Special Instructions:
  • Contraindicated in patients w/ renal disease, history of blood dyscrasias, CHF, exfoliative dermatitis, necrotizing enterocolitis, history of anaphylactic reactions
  • Discontinue therapy if platelet count falls <100,000/mm³, WBC count is <4000, or if granulocyte count is <1500/mm³
• Dosage Guidelines:
  • 6 mg PO 24 hrly or 3 mg PO 12 hrly
  • May increase dose to 3 mg PO 8 hrly after 4-6 mth
  • Max dose: 9 mg/day

• Adverse Reactions:
  • CNS effects (fever, malaise); GI effects (N/V, diarrhea); Hematologic effects (leukopenia, thrombocytopenia); Other effects (increased LFT, myalgia, rarely pancreatitis)
  • Increased risk of neoplasia w/ chronic use
• Special Instructions:
  • Use w/ caution in patients w/ hepatic or renal impairment, w/ Thiopurine S-methyltransferase (TPMT) deficiency
  • There have been reports of increased risk of HSTLC development, particularly in adolescents & young adults
    • Monitor for signs & symptoms or malignancy (eg splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, wt loss)
  • Monitor CBC & platelets, LFT, total bilirubin, TPMT genotyping or phenotyping
• Dosage Guidelines:
  • 1 mg/kg PO 12-24 hrly
  • May increase dose by 0.5 mg/kg/day at 4 wk intervals
  • Max dose: 2.5 mg/kg/day

• Adverse Reactions:
  • GI effects (abdominal pain, diarrhea, nausea, dyspepsia); CNS effects (tremors, headache); CV effects (hypertension, edema); Other effects (gingival hyperplasia, hirsutism, hypertrichosis, renal dysfunction, nephropathy, elevated creatinine, increased triglycerides, infection)
• Special Instructions:
  • Avoid prolonged sun exposure, tanning booths & sunlamps
  • Avoid in patients w/ renal dysfunction, uncontrolled hypertension, uncontrolled infections, persistently raised creatinine, malignancy, porphyria
  • Monitor renal & hepatic function, BP, serum electrolytes & lipids regularly
  • Vaccination w/ live-virus vaccines are not recommended
  • Commercially available oral products differ in their bioavailability; use caution when switching from one product to another
• Dosage Guidelines:
  • 2.5 mg/kg/day PO divided 12 hrly for 6-8 wk
  • If the clinical effect is insufficient, may be increased to max dose
  • Max dose: 4 mg/kg/day
  • Discontinue treatment if no response after 3-4 mth of use

• Show efficacy as monotherapy or in combination therapy
• Hydroxychloroquine is recommended in patients w/ low disease activity & w/o poor prognostic factors
• Adverse Reactions:
  • CNS effects (dizziness, headache, nervousness, seizure, vertigo); Dermatologic effects (alopecia, rash); GI effects (N/V, abdominal pain); Other effects (visual symptoms, muscle weakness)
• Special Instructions:
  • Use w/ caution in patients w/ hepatic or renal impairment, G6PD deficiency, psoriasis, porphyria
  • Perform baseline ophthalmologic exam & every 3 mth
  • Test periodically for muscle weakness
  • Baseline assessment of hepatic & renal function is recommended
• Dosage Guidelines:
  • Initial Dose: 400-800 mg PO 24 hrly in divided doses
  • Maintenance Dose: 200-400 mg PO 24 hrly
  • Max dose: 6.5 mg/kg/day

• Recommended as part of the initial treatment strategy in patients w/ contraindication to or intolerance of Methotrexate
• It is recommended for all degrees of disease activity, irrespective of poor prognostic features
• Adverse Reactions:
  • GI effects (diarrhea, N/V); CV effects (hypertension, chest pain, edema, palpitation); CNS effects (headache, dizziness); Other effects (increase susceptibility to infection, alopecia); Rarely, hepatologic effects, dermatologic reactions (eg Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Special Instructions:
  • Use w/ caution in patients w/ hematologic disorders, renal impairment
  • Contraindicated in patients w/ significant hepatic impairment, bone marrow dysplasia
  • TB screening prior to treatment
  • Monitor CBC, LFT
• Dosage Guidelines:
  • Loading dose: 100 mg PO 24 hrly x 3 days
  • Maintenance dose: 10-20 mg PO 24 hrly

• Recommended to be part of the initial treatment strategy in active RA
• Has a good long-term safety profile
• Recommended for all degrees of disease activity, irrespective of poor prognostic features
• Can increase the efficacy of biologic DMARDs when used in combination
• Considered as one of the most active compounds in terms of frequency of remissions & time to onset of action
• Provides a good risk-benefit ratio
• Adverse Reactions:
  • CNS effects (dizziness, fever, seizure); GI effects (N/V, loss of appetite, abdominal pain, diarrhea); Hematologic effects (anemia, leukopenia, thrombocytopenia), Other effects (alopecia, potentially fatal dermatologic reactions eg toxic epidermal necrolysis & Stevens-Johnson syndrome, impairment of fertility, oligospermia)
  • Low-dose Methotrexate has been associated w/ development of malignant lymphomas
  • Use may predispose patients to opportunistic infection
  • Dosage exceeding 20 mg/wk may cause a higher incidence & severity of adverse events
• Special Instructions:
  • Contraindicated in patients w/ alcoholic liver disease, pre-existing blood dyscrasias
  • Use w/ caution in patients w/ peptic ulcer disease, ulcerative colitis, renal impairment
  • May cause folic acid deficiency
    • Some experts recommend concomitant administration of folic acid at 5 mg/wk, except on the day of Methotrexate
  • Monitor CBC w/ platelets, serum creatinine & LFT
• Dosage Guidelines:
  • 7.5 mg PO once wkly, adjust as needed or 5-15 mg IM once wkly
  • Maybe increased by 5 mg/wk
  • Max dose: 20-25 mg PO once wkly

• Adverse Reactions:
  • CV effect (vasculitis); CNS & behavioral effects (fever, anxiety, agitation, psychiatric disturbance); Dermatologic effects (dermatomyositis, exfoliative dermatitis; GI effects (anorexia, diarrhea, epigastric pain, N/V); Hematologic effects (aplastic anemia, leukocytosis, thrombocytopenia, agranulocytosis); Other effects (alopecia, hypoglycemia, thyroiditis, proteinuria)
• Special Instructions:
  • Contraindicated in patients w/ renal insufficiency
  • Use w/ caution in patients on other hematopoietic-depressant drugs
  • Monitor CBC, urine full examination microscopy elements
• Dosage Guidelines:
  • 1st 4 wk: 150-250 mg PO 24 hrly
  • 2nd 4 wk: 250-450 mg PO 24 hrly
  • 3rd 4 wk: 300-600 mg PO 24 hrly
  • May be increased by increments of 50-150 mg at 4-12 wkly intervals to a total of 750 mg/day
  • Maintenance dose: 300-450 mg/day

• Recommended as part of the initial treatment strategy in patients w/ contraindication to or intolerance to Methotrexate
• One of the most active compounds in terms of frequency of remissions & time to onset of action
• Provides a good risk-benefit ratio
• Recommended by some group to be used in all degrees of disease activity & in those w/ absence of poor prognostic factors
• Adverse Reactions:
  • CNS & behavioral effects (headache, dizziness, fever, insomnia, depression); Dermatologic effects (pruritus, urticaria, rashes such as toxic epidermal necrolysis, Stevens-Johnson syndrome, drug rash w/ eosinophilia & systemic symptoms ); GI effects (N/V, loss of appetite, abdominal pain); Hematologic effects (anemia, leukopenia, thrombocytopenia), Other effects (oligospermia, cyanosis, discoloration of body fluids, aseptic meningitis, ocular complications, alopecia)
• Special Instructions:
  • Contraindicated in patients w/ porphyria, GI or GU obstruction, blood dyscrasias
  • Use w/ caution in patients w/ severe allergies or bronchial asthma, G6PD deficiency, hepatic & renal impairment
  • May cause folic acid deficiency, consider giving folate supplement
  • Monitor LFT & CBC during the 1st 3 mth of treatment & periodic monitoring of kidney function is recommended
• Dosage Guidelines:
  • Initial Dose: 500 mg PO 24 hrly x 1 wk
  • Increase the dose by 500 mg 12 hrly wkly
  • Maintenance Dose: 2 g/d PO in divided 12 hrly
  • Max dose: 3 g/day

• Biologic DMARDs generally target cytokines or their receptors or are directed against other cell surface molecules
• Monotherapy recommended for early RA patients w/ good prognosis including all levels of disease activity (low to high)
• ACR recommends killed (pneumococcal, influenza, hepatitis), recombinant (HPV) and live attenuated (herpes zoster [except for TNF inhibitors and non-TNF biologics]) vaccines before and during initiation of DMARD therapy

• Eg Adalimumab, Certolizumab pegol, Etanercept, Infliximab, Golimumab
  • Adalimumab is a human-sequence antibody that specifically binds to TNF-α & blocks interaction w/ cell-surface TNF-α receptors to neutralize its biological function (ie changes in adhesion molecule levels that causes leukocyte migration)
  • Certolizumab pegol is a TNF-α specific Fab fragment of humanized monoclonal antibody which highly binds w/ soluble & membrane-bound TNF-α that causes inhibition of its activity
  • Etanercept is a recombinant human TNF-α receptor fusion protein that interferes w/ inflammatory cascade by binding to TNF-α & then blocking its interaction w/ cell-surface receptors
  • Infliximab is a chimeric monoclonal antibody that neutralizes TNF-α function by binding to it
  • Golimumab is a human monoclonal antibody specific for TNF-α & prevents its interaction by forming high affinity complexes
• Recommended for the following:
  • Early RA patients w/ high disease activity & poor prognosis (w/ or w/o Methotrexate)
  • Established RA patients w/ low disease activity & good prognosis where DMARD monotherapy w/ added Methotrexate, Hydroxychloroquine & Leflunomide have failed
  • Established RA patients where 1st TNF inhibitor regimen has failed (ACR recommends switching to another TNF inhibitor or replacing the TNF inhibitor w/ Abatacept, Rituximab or Tocilizumab)
  • Adalimumab, Etanercept & Certolizumab may be given as monotherapy in patients w/ intolerance of Methotrexate or if treatment w/ Methotrexate is considered to be inadequate
  • Certolizumab in combination w/ Methotrexate is indicated for the treatment of moderate-severe RA in patients whose response to non-biological DMARDs including Methotrexate, has been inadequate
• All have been shown to have similar efficacy for clinical remission
• Not recommended in patients w/ severe, active & progressive RA not previously treated w/ Methotrexate or other DMARDs
• Reassess treatment effects every after 3 mnths
• Have been shown to increase the risk of serious infection, & risk of malignancy
• Contraindicated in patients with severe CHF
• Adverse Reactions:
  • CNS effects (headache, dizziness); GI effects (abdominal discomfort, N/V); Other effects (local inj site reaction)
  • Allergic/hypersensitivity reactions rarely occur
    • Hypersensitivity reaction may occur w/in 2 hr of Infliximab infusion
  • Rare cases of autoimmune disorder have been reported
  • Serious & potentially fatal infections (eg bacterial, mycobacterial, viral, fungal infections) have been reported
    • Reports of TB reactivation of latent infection & new infection have been noted
    • Rare reactivation of hep B virus infection have occurred
  • There have been reports of increased risk of HSTLC development, particularly in adolescents & young adults
  • Severe hepatic reactions have been reported during treatment w/ Infliximab
• Special Instructions:
  • Do not give to patients w/ active chronic or localized infection
  • Use w/ caution in patients w/ hematologic disorders, heart failure, history of new/recurrent infections, w/ conditions that predispose to infection (eg DM), demyelinating CNS disorders
    • Infliximab should be used w/ caution in patients w/ history of seizure
  • Medication & equipment for immediate management of hypersensitivity reactions should be available
  • Monitor for signs & symptoms or malignancy (eg splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, wt loss)
  • Temporarily discontinue Etanercept use in patients w/ significant exposure to Varicella virus
    • May treat w/ Varicella zoster immunoglobulin
  • Discontinue Infliximab use in patients developing w/ significant CNS adverse reaction, jaundice or liver enzyme ≥5x upper limit of normal
  • Hepatitis & TB screening is recommended prior to treatment
  • Update immunization status of the patient prior to start of therapy
• Dosage Guidelines:

• 40 mg SC as single dose every other wk
• May increase dosing frequency to 40 mg/wk if not taken concomitantly w/ Methotrexate

• Initial dose: 400 mg SC 24 hrly at wk 2 & 4, then 200 mg SC every other wk
• Maintenance dose: 400 mg SC 4 wkly

• 25 mg SC twice wkly or 50 mg SC once wkly

• 50 mg SC once a mth

• Initial dose: 3 mg/kg IV infusion over 2 hr, followed by additional 3 mg/kg doses at 2 & 6 wk after the 1st infusion, then every 8 wk thereafter
• Dose may be increased up to 10 mg/kg after 22 wk. May be given in combination w/ Methotrexate

• Eg Abatacept, Rituximab, Tocilizumab, Tofacitinib
• Reassess treatment effects after 6 mnths instead of 3 mnths due to longer peak time in non-TNF biologics
• Abatacept or Rituximab is recommended for established RA patients w/ low disease activity & poor prognosis or moderate-high disease activity intolerant or unresponsive to Methotrexate monotherapy or combination DMARD therapy
• Abatacept is recommended for patients w/ contraindication to Rituximab, or when Rituximab is withdrawn due to adverse effect
• Treatment period of Rituximab should not be more frequent than every 6 mth
• Abatacept-Methotrexate combination is recommended when double DMARD regimen results in treatment failure or toxicity
• Switching to Tocilizumab is recommended when Rituximab or Abatacept regimen results in treatment failure after 6 mnths
• Resuming or starting Rituximab is recommended in RA patients with a previously treated melanoma skin cancer, lymphoproliferative malignancy, solid malignancy or nonmelanoma skin cancer w/in the last 5 years

• Adverse Reactions:
  • CNS effects (headache, dizziness, fever); GI effects (abdominal discomfort, nausea); Other effects (infection, hypertension, rash, back pain, infusion-related reaction)
  • Allergic reactions may occur
  • Drug use may affect defenses against malignancies
    • Clinical trials have noted increased risk for lymphoma & lung cancer
• Special Instructions:
  • Use w/ caution in patients w/ COPD, w/ history of new/recurrent infections, w/ conditions that predispose patient to infection
  • Hepatitis & TB screening prior to treatment
  • Update immunization status of the patient prior to start of therapy
• Dosage Guidelines:
  • <60 kg: 500 mg
  • 60-100 kg: 750 mg
  • >100 kg: 1000 mg
  • Dose according to body wt & administered as a 30-min IV infusion
  • Repeat dose at 2 & 4 wk after the 1st infusion & every 4 wk thereafter

• Adverse Reactions:
  • CV effects (hypertension, edema); CNS effects (fever, fatigue, headache); Dermatologic effects (rash, pruritus, angioedema); GI effects (nausea, diarrhea, wt gain, abdominal pain)
  • New/reactivation of viral infections, infusion-related reactions, hypersensitivity reactions & mucocutaneous reactions have been reported
• Special Instructions:
  • Use w/ caution in patients w/ pre-existing CV & pulmonary disease
  • Vaccination w/ live-virus vaccines are not recommended
  • Hepatitis screening is recommended prior to treatment
• Dosage Guidelines:
  • For patients receiving Rituximab w/ glucocorticoid (Methylprednisolone 100 mg IV or its equivalent): Administer glucocorticoid 30 min prior to each infusion to reduce the incidence & severity of infusion reactions
  • When used in combination w/ Methotrexate: Rituximab 1 g IV infusion on days 1 & 15 (for a total of 2 doses/course)
  • Subsequent courses of Rituximab & Methotrexate may be administered every 24 wk or based on clinical evaluation, but not sooner than every 16 wk

• Adverse Reactions:
  • CV effects (hypertension, edema); Dermatologic effects (pruritus, urticaria); CNS effects (headache, dizziness); GI effects (abdominal discomfort, stomatitis, wt gain); Other effects (neutropenia, thrombocytopenia, increased triglycerides, elevated LFT, infusion-related reactions)
  • One case of fatal anaphylaxis has been reported
  • Serious & potentially fatal infections (eg bacterial, mycobacterial, viral, fungal infections) have been reported
    • Reports of TB both reactivation of latent infection & new infection have been noted
• Special Instructions:
  • Use is not recommended in patients w/ hepatic impairment
  • Use w/ caution in patients w/ demyelinating CNS disorders or w/ risk of GI perforation
  • Latent TB screening is recommended prior to treatment
• Dosage Guidelines:
  • Initial dose: 4 mg/kg IV infusion over 1 hr, every 4 wk
  • May increase dose to 8 mg/kg every 4 wk
  • Max dose: 800 mg/dose every 4 wk

• Adverse Reactions:
  • Respiratory effects (upper respiratory tract infection, nasopharyngitis, pneumonia, tuberculosis, dyspnea, cough, sinus congestion); GI effects (diarrhea, abdominal pain, dyspepsia, N/V, gastritis); Genitourinary effects (UTI); Dermatologic effects (cellulitis, rash, erythema, pruritus); Hematologic effects (neutropenia, anemia); Other effects (herpes zoster infection, liver enzyme elevation, lipid profile elevations, hypertension, headache, fatigue)
• Special Instructions:
  • Use w/ caution in patients w/ active infections, increased risk for GI perforations, lymphomas & other malignancies, severe hepatic impairment
  • Monitor CBC & lipid profile
• Dosage Guidelines:
  • 5 mg PO 12 hrly

• For early RA, combination of DMARDs (including Methotrexate & another DMARD w/ short-term corticosteroids) can be considered as 1st-line treatment
• Recommended combinations include double & triple therapy (Methotrexate, Hydroxychloroquine & Sulfasalazine)
• Examples for double DMARD therapy include Methotrexate & Hydroxychloroquine, Methotrexate & Leflunomide, Methotrexate & Sulfasalazine, & Sulfasalazine & Hydroxychloroquine
• For patients where DMARD combination therapy is not appropriate, start DMARD monotherapy
• Combinations of non-biological & biological DMARDs have been used to treat moderate-severe RA
• Most combinations use Methotrexate as a background drug
• Recommended for all early RA patients w/ poor prognosis including all levels of disease activity (low to high), & established RA patients w/ low disease activity & poor prognosis or moderate-high disease activity
• Combination therapy of Methotrexate & biologic DMARDs may be considered in DMARDs naive patients w/ poor prognostic factors

• Used as an adjunct to DMARD & NSAID therapy to provide pain relief

• Adverse Reactions:
  • Hematologic effects (anemia, neutropenia); Dermatologic effect (rash); Hepatic effects (increase bilirubin, alkaline phosphatase); Metabolic effects (increased uric acid, glucose); Other effects (nephropathy, anaphylaxis)
• Special Instructions:
  • Avoid use in patients w/ severe hepatic or active liver disease
  • Used w/ caution in patients w/ chronic malnutrition, severe renal impairment, alcoholic liver disease, G6PD deficiency
• Dosage Guidelines:
  • 325-650 mg PO 4-6 hrly or 1000 mg PO 6-8 hrly
  • Max dose: 4 g/day

¹Combination w/ various opioid analgesics are available. Please see the latest MIMS for prescribing information.

• Adverse Reactions:
  • GI effects (N/V, dyspepsia, ulceration, hematemesis); Hematologic effect (iron deficiency anemia after long-term use, hypoprothrombinemia); Dermatologic effects (urticaria, angioedema); Hypersensitivity reactions (bronchospasm, dyspnea); Other effect (hepatotoxicity)
  • Salicylism (dizziness, tinnitus, deafness, sweating, N/V, headache, confusion) may occur after repeated use of large doses
• Special Instructions:
  • May be given w/ food to decrease GI effects
  • Avoid use in patients w/ hemophilia or other hemorrhagic disorders, history of allergy to other NSAIDs, severe renal or hepatic impairment, pregnancy (esp 3rd trimester)
  • Use w/ caution in patients prone to dyspepsia, w/ gastric ulcer, asthma or allergic disorders, renal or hepatic impairment, dehydration, uncontrolled hypertension, G6PD deficiency, DM
  • Aspirin should be stopped several days before surgery
• Dosage Guidelines:
  • 3-6 g/day PO in divided doses
  • Pain & inflammation associated w/ musculoskeletal joint disorder:
    • Initial: 2.4-3.6 g/day in divided doses
    • Maintenance: 3.6-5.4 g/day

• Adverse Reactions:
  • GI effects (N/V, constipation, dry mouth); CNS effects (drowsiness, confusion, dizziness, headache, changes in mood); CV effects (bradycardia, tachycardia, palpitations)
  • Large doses may cause resp depression/failure, renal failure, hypotension, deepening coma
• Special Instructions:
  • Avoid use in patients w/ acute resp depression, obstructive airway disease, acute alcoholism, convulsive disorder, head injuries, increased intracranial pressure, at risk of paralytic ileus, or in patients who require mental alertness (eg driving, operating machines)
  • Use w/ caution in patients w/ hypothyroidism, asthma, renal or hepatic impairment, adrenocortical insufficiency, prostatic hyperplasia, hypotension, shock, inflammatory or obstructive bowel disease, myasthenia gravis
• Dosage Guidelines:
  • 50-100 mg PO 4-6 hrly
  • Max dose: 400 mg/day

¹Combination w/ Paracetamol is available. Please see the latest MIMS for prescribing information.

• Have been shown to improve symptoms of RA & reduce radiological damage
• Commonly used to bridge the time until DMARDs are effective
• Timely dose reductions & cessation are important because of the adverse effects associated w/ long-term use of corticosteroids
  • In cases of persistent remission involving combination therapy w/ DMARDs, corticosteroids should be tapered first
• Intra-articular corticosteroids are used to provide rapid, symptomatic relief in the target joints
  • May be administered to any joint not >3-4x/yr
• Oral supplementation w/ daily Ca (1500 mg) & vit D (400-800 IU) should be given to limit bone demineralization

• Adverse Reactions:
  • Local effects (post-injection flare, sterile abscess, thrombophlebitis)
• Special Instructions:
  • Systemic absorption should always be considered
  • Use w/ caution in patients w/ preexisting psychiatric conditions, heart failure, DM, GI diseases, hepatic impairment including cirrhosis, myasthenia gravis, cataracts &/or glaucoma, osteoporosis, renal impairment, history of seizure disorder, thyroid disease, following acute MI
• Dosage Guidelines:

4.2.1.1.1. Dexamethasone
• 0.2-6 mg/dose IA once every 3-5 days or once every 2-3 wk
4.2.1.1.2. Triamcinolone (Triamcinolone acetonide)

• Small joints: 2.5-5 mg
  • Max dose: 10 mg
• Large joints: 5-15 mg
  • Max dose: 40 mg
4.2.1.2. Potent

4.2.1.2.1. Betamethasone (Betamethasone Na phosphate)
• Small joints: 0.25-0.5 mL IA
• Medium joints: 0.5-1.0 mL IA
• Large joints: 1-2 mL IA

• Unacceptable levels of pain
• Persistent localized synovitis
• Worsening joint function (ie instability or severe loss of range of joint motion)
• Progressive deformity

• Carpal tunnel release
• Cervical C1-C2 fusion
• Finger small joints fusion/arthroplasty
• Synovectomy
• Tendon reconstruction
• Total joint arthroplasty

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• Eg CBC, serum creatinine, LFT, hepatitis B & C screening, ophthalmologic exam, latent TB screening (for biological DMARDs, w/ CXR)
• Recommended prior to resuming or increasing therapy w/ DMARDs
• It is important to monitor for toxicity due to the potential risks of serious adverse effects of DMARDs

• Disease activity should be measured & documented regularly
  • Moderate-high disease activity: monthly
  • Sustained low disease activity: every 6 mth
  • Clinical remission: every 6 mth (w/ DAS & DAS28)
  • Sustained remission: every 3-6 mth
• Consider structural changes, comorbidities, & functional impairment when formulating treatment decisions on follow-ups