TOC  |  Rheumatology  
Rheumatoid Arthritis                                                              See  Pain / NSAID Med                         

Major Sx includes symmetrical plyarthritis with joint swelling & tenderness & morning stiffness lasting for > 1 hour. Subcutaneous nodules, + rheumatoid factor, & x-ray evident erosions or juxta-articular osteoporosis are further characteristics of RA.

ACR Criteria for Rheumatoid Arthritis   (*symptoms must be present for > 6 weeks)

  1. Morning Stiffness > 1 hour*
  2. Arthritis of three or more joints*
  3. Arthritis of hand joints*
  4. Symmetric arthritis*
  5. Rheumatoid nodules
  6. Serum rheumatoid factor >1:160
  7. Radiographic changes consistent with RA

If more than 4 are positive then patient has RA. 

Treatment:       

The goals of Rx are to alleviate pain, control inflmmation, preserve the joint & daily activity function , & to prevent joint destruciton.

Disease-Modifying Anti-Rheumatic Drugs (DMARD)

Drugs

Toxic effects requiring follow-up

 Monitoring studies
Hydroxychloroquine (Plaquenil)
200-600 mg/day in 1 or 2 doses with meal		 macular damage yearly eye exam
Methotrexate
7.5 - 25 mg PO. subc, IM/wk		 myelosuppresion, hepatic fibrosis, cirrhosis, pulm. infiltrates or fibrosis. CBC,LFT.
Folate 1 mg supplement
Azathioprine (Imuran)
50-150 mg/d in 1-3 doses with meal		 myelosuppresion, hepatotoxicity, lymphoproliferative disorders CBC, LFT q1-2wks
Prednisone /Corticosteroids
2-15 mg/d PO; 20-60 mg/d for extra-articular vasculitis. 		 hypertension, hyperglycemia, osteoporosis BP, glucose, bone density scan
Cyclosporin
2.5 -5 mg/kg/d in 1 or 2 doses		 renal insufficiency, anemia, hypertensio, hirsutism Creat, lytes,CBC, LFT
Penicillamine (Cuprimine)
125-250 mg/d, max<1500mg/d		 myelosuppresion, proteinuria CBC, UA
Etanercept (Enbrel)  subc.
10 or 25 mg subc 2x/wk, x 6 months
(AIM March 16, 1999;130:478 - Larry Moreland)		 injection site reaction, flu-like Sx .
Leflunomide (Arava) PO 
100 mg/d x 3 d, then 10-200 mg/d		 thrombocytopenia, hepatotoxicity, diarrhea CBC, LFT q4-8wks
Adalimumab (Humira) 40 mg subc q other week
Infliximab (Remicade)  IV  
TNF-alpha antagonist 3 mg/kg IV q8wks		 flu-like Sx, autoantibody development .
Gold IM
10 mg first, then 25 mg next wk, then 25-50 mg/wk;
Gold PO Auranofin (ridaural) cap
3-9 mg/d in 1-3 doses		 Myelosuppresion, proteinuria CBC, UA
Sulfasalazine
2-3g/d in 2-4 doses		 myelosuppresion CBC, LFT, Creat q2-4wks
Minocycline
200 mg/d in 2 doses on empty stomach		 photosensitivity, skin discoloration, GI upset, dizziness, drug-induced hepatitis .

Scenarios Illustrating the Practical Application of Therapeutic Strategies for RA

  1. Newly diagnosed RA in a young patient with presence of RF & mild disease (few joints involved & ESR <30)
    Rx: Hydroxychloroquine 400 mg/d with or without NSAID med, and prednisone 3-5 mg/d over a 1-3 months period; sulfasalazine, upto 3 g/d in 2 divided doses, is an acceptable alternative.
  2. New onset RA with pronounced Sx including fatigue, low-grade fever, weight loss, & polyarticular disease.
    Rx: Methotrexate, with NSAID med, and prednisone 5-15 mg/d; taper prednisone over a 3-4 months period if possible. If adequate control cannot be achieved after the initial 6-8 wks of Rx, consider adding hydroxychloroquine, sulfasalazine, or both to this regimen; a frequent cause of "Methotrexate failure" is an inadequate dose of methotrexate (providing that the patient is able to tolerate the higher doses)
  3. Patient with established mild disease.
    Rx: hydroxychloroquine 400 mg/d, with or without an NSAID, and prednisone 3-5 mg/d over 1-3 months period; sulfasalazine, up to 3 g/d in 2 divided doses is an acceptable alternative.
  4. Established RA in whom optimal dose of methotrexate is partially effective.
    NSAID, if they add measurably to Sx control; prednisone 5-15 mg/d
    *Initiate combination: Rx: may add hydroxychloroquine, sulfasalazine, or both.
    *If combination Rx with hydroxychloroquine, sulfasalazine, or both is ineffective:
    Rx: Discontinue hydroxychloroquine & sulfasalazine; add leflunomide, azathioprine, cyclosporine, or possibly gold.
    *If combination Rx with methotrexate & cyclosporine, leflunomide, or azathioprine is poorly tolerated or ineffective:
    Rx: Continue methotrexate but discontinue the combination drug & add etanercept or infliximab.  TNF-alpha antagonists should be avoided in patients with chronic infections, draining nodules, or history of TB or TB exposure; discontinue these agents 7-10 days before & after major surgery.
  5. Established RA in whom methotrexate is effective, not tolerated, or contraindicated.
    Rx: For mild disease: leflunomide, sulfasalazine, & azathioprine.
    For severe disease: cyclosporin & combinations of DMARDs such as sulfasalazine, hydroxychloroquine, & others, or etanercept or infliximab; gold may be considered, particularly in combination with any of these therapies, although it is rarely tolerated or useful.
  6. Patients with established seronegative RA.
    Rx: Of importance, decision about use & aggressiveness of DMARD Rx should not be based solely on the presence or absence of the rheumatoid factor (RF).  Rx must be tailored to the disease manifestations in the individual patient.

Ref:
Mayo Clin Proc. Jan. 2000;75:69 - Eric Matteson   "Review  of Current Rx for RA"
New treatments for rheumatoid arthritis -Kenneth H. Fye  VOL 106 / NO 4 / OCTOBER 1, 1999 / POSTGRADUATE MEDICINE  
Rheumatoid Arthritis (KP Intranet)

     
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11092004