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Rheumatoid Arthritis - DMARD Therapy

Background

This calculator provides general pharmacologic treatment guidelines for rheumatoid arthritis (RA) based on the latest evidence (Oct 2017). Medications listed will have direct links to the latest package insert. Based on the selections below, this tool will provide possible treatment strategies that have been studied.  This initial program covers only disease-modifying antirheumatic drugs (DMARDs):  1,2,3

  • Nonbiologic disease-modifying antirheumatic drugs (DMARDs)
  • Biologic DMARDs, which include:
    • TNF-α inhibitor biologics and
    • Non-TNF biologics.

Instructions: review each section and make a selection based on the information provided.

Duration

    

Disease activity



More infoLow  |  High

Prognosis:   

  

 More info:    Good  |  Poor

Dosing



Methotrexate (Trexall)
: Rheumatoid arthritis:   Dosing:  Initially: Oral: 7.5 mg once weekly or 2.5 mg q12h for 3 doses/week - adjust dose gradually based on response.    IM: 7.5 mg once weekly - adjust dose gradually based on the optimal response.   Usual maintenance:  Oral or IM: 7.5-15 mg once weekly.    [Regardless of the route of administration, doses above 20mg/week are associated with increased risk of toxicity.]  Consider adding folic acid (~5mg/week) to reduce possible adverse reactions (hematologic, gastrointestinal, and hepatic).  Folic acid should not be administered on the same day as methotrexate. Methotrexate may also be given subcutaneously. Package Insert / pdf.


Leflunomide (Arava): Rheumatoid arthritis:   Dosing: The recommended dosage of ARAVA is 20 mg once daily. Treatment may be initiated with or without a loading dose, depending upon the patient's risk of ARAVA-associated hepatotoxicity and ARAVA-associated myelosuppression. The loading dosage provides steady-state concentrations more rapidly.  
>For patients who are at low risk for ARAVA-associated hepatotoxicity and ARAVA-associated myelosuppression the recommended ARAVA loading dosage is 100 mg once daily for 3 days. Subsequently administer 20 mg once daily.
>For patients at high risk for ARAVA-associated hepatotoxicity (e.g., those taking concomitant methotrexate) or ARAVA-associated myelosuppression (e.g., patients taking concomitant immunosuppressants), the recommended ARAVA dosage is 20 mg once daily without a loading dose.

The maximum recommended daily dosage is 20 mg once per day. Consider dosage reduction to 10 mg once daily for patients who are not able to tolerate 20 mg daily (i.e., for patients who experience any adverse events.  Package Insert / pdf.


Hydroxychloroquine  (Plaquenil) - Rheumatoid arthritis: The action of hydroxychloroquine is cumulative and may require weeks to months to achieve the maximum therapeutic effect.  Dosing:  Initial adult dosage: 400 mg to 600 mg (310 to 465 mg base) daily, administered as a single daily dose or in two divided doses. In a small percentage of patients, side effects may require temporary reduction of the initial dosage.  Maintenance adult dosage: When a good response is obtained, the dosage may be reduced by 50 percent and continued at a maintenance level of 200 mg to 400 mg (155 to 310 mg base) daily, administered as a single daily dose or in two divided doses.  Do not exceed 600 mg or 6.5 mg/kg (5 mg/kg base) per day, whichever is lower, as the incidence of retinopathy has been reported to be higher when this maintenance dose is exceeded.   Corticosteroids and salicylates may be used in conjunction with PLAQUENIL, and they can generally be decreased gradually in dosage or eliminated after a maintenance dose of PLAQUENIL has been achieved.  Package Insert / pdf.


Sulfasalazine (Azulfidine):  Rheumatoid arthritis:  Dosing:  Initially: Oral: 500mg once daily or 1 g/day (500mg bid).   It is advisable to initiate therapy with a lower dosage of sulfasalazine delayed release tablets, e.g., 0.5 to 1 g daily, to reduce possible gastrointestinal intolerance. Usual maintenance:  Oral: Increase weekly to 1 gram twice daily (Consideration can be given to increasing the daily dose of sulfasalazine delayed release tablets to 3 g if the clinical response after 12 weeks is inadequate.).  Not recommended in renal of hepatic impairment.  Package Insert / pdf.



Adalimumab (Humira)- Rheumatoid arthritis:   Dosing:  Administered by subcutaneous injection - 40 mg every other week. Some patients with RA not receiving methotrexate may benefit from increasing the frequency to 40 mg every week. Methotrexate (MTX), other non-biologic DMARDS, glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or analgesics may be continued during treatment with HUMIRA.  Package Insert / pdf.


Certolizumab pegol (Cimzia) - Rheumatoid arthritis:  Dosing:  CIMZIA is administered by subcutaneous injection. 400 mg initially and at Weeks 2 and 4, followed by 200 mg every other week; for maintenance dosing, 400 mg every 4 weeks can be considered.  When a 400 mg dose is needed (given as two subcutaneous injections of 200 mg), injections should occur at separate sites in the thigh or abdomen. Before initiation of therapy with CIMZIA, all patients must be evaluated for both active and inactive (latent) tuberculosis infection. CIMZIA may be used as monotherapy or concomitantly with non-biological disease modifying anti-rheumatic drugs (DMARDs).  The use of CIMZIA in combination with biological DMARDs or other tumor necrosis factor (TNF) blocker therapy is not recommended. Package Insert / pdf.



Etanercept (Enbrel):: Rheumatoid arthritis:  Dosing:  50 mg once weekly administered by subcutaneous injection with or without methotrexate (MTX). Alternatively: 25 mg twice weekly.  Package Insert / pdf.



Golimumab (Simponi): Rheumatoid arthritis:  Dosing: The SIMPONI dose regimen is 50 mg administered by subcutaneous injection once a month. For patients with rheumatoid arthritis (RA), SIMPONI should be given in combination with methotrexate. For patients with RA, PsA, or AS, corticosteroids, non-biologic DMARDs, and/or NSAIDs may be continued during treatment with SIMPONI.  Package Insert / pdf.



Infliximab (Remicade) Dosing: Rheumatoid arthritis:   In conjunction with methotrexate, 3 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Some patients may benefit from increasing the dose up to 10 mg/kg or treating as often as every 4 weeks. [REMICADE is administered by intravenous infusion over a period of not less than 2 hours. ]   Package Insert / pdf.




Tocilizumab (Actrema) - IL-6 Inhibitor. Rheumatoid arthritis: Note: May be combined with nonbiologic disease-modifying antirheumatic drugs (DMARDs) but NOT with biologic DMARDs.
Dosing:   Initial: 4 mg/kg IV once every 4 weeks.  May be increased to 8 mg/kg once every 4 weeks based on clinical response (maximum dose: 800 mg).   Subcutaneous (SC):   <100 kg: 162 mg once every other week; increase to 162 mg once every week based on clinical response.   geq100 kg: 162 mg once every week. Package Insert / pdf.



Tofacitinib (Xeljanz) - JAK Kinase Inhibitor.  Rheumatoid arthritis:  XELJANZ/XELJANZ XR may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). Limitations of Use: Use of XELJANZ/XELJANZ XR in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

It is recommended that XELJANZ/XELJANZ XR not be initiated in patients with an absolute lymphocyte count less than 500 cells/mm3, an absolute neutrophil count (ANC) less than 1000 cells/mm3 or who have hemoglobin levels less than 9 g/dL.

Dosing
:  Recommended dose of XELJANZ is 5 mg twice daily. Recommended dose of XELJANZ XR is 11 mg once daily. Recommended dose in patients with moderate and severe renal impairment and moderate hepatic impairment is XELJANZ 5 mg once daily. Use of XELJANZ/XELJANZ XR in patients with severe hepatic impairment is not recommended.

Selected drug interactions:  Potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g., ketoconazole): Recommended dose is XELJANZ 5 mg once daily.  One or more concomitant medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole): Recommended dose is XELJANZ 5 mg once daily.  Potent CYP inducers (e.g., rifampin): May result in loss of or reduced clinical response.   Package Insert / pdf.



Abatacept (Orencia) - Costimulation Modulator.  Rheumatoid arthritis (RA).
Dosing
: Adults: Dose is based on body weight:  <60 kg: 500 mg.   60 to 100 kg: 750 mg.  >100 kg: 1,000 mg.    IV infusion:  Initially start IV infusion at the weight-based dose, then repeat the IV infusion (using the same weight-based dose) at 2 weeks and 4 weeks after the initial infusion, and then every 4 weeks thereafter.
Subcutaneous (SC): Administer by subcutaneous injection once weekly with or without an intravenous loading dose. For patients initiating therapy with an intravenous loading dose, administer a single intravenous infusion (as per body weight categories above), followed by the first 125 mg subcutaneous injection given within a day of the intravenous infusion.   Package Insert / pdf.

Rituximab (Rituxan) -Anti CD20 Antibody.  Rheumatoid arthritis: The dose for RA in combination with methotrexate is two-1000 mg intravenous infusions separated by 2 weeks (one course) every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. Methylprednisolone 100 mg intravenous or equivalent glucocorticoid is recommended 30 minutes prior to each infusion. Package Insert / pdf.

 

References

  1. Wahl K, Schuna AA. Rheumatoid Arthritis. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy: A pathophysiologic approach. 9th ed. New York: McGraw-Hill Medical; c2014. Chapter 72.

  2. Saag KG, Teng GG, Patkar NM, Anuntiyo J, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008;59:762–784.

  3. Singh JA, Saag KG, et al.2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care & Research DOI 10.1002/acr.22783 VC 2015, American College of Rheumatology. Link: https://www.rheumatology.org/Portals/0/Files/ACR%202015%20RA%20Guideline.pdf






Disclaimer

All calculations must be confirmed before use. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.   Read the disclaimer
 

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