Pharmacist Disease State Guides
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      Rheumatoid Arthritis

      Disease State Overview

      ​​Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes pain, swelling, stiffness, and loss of function in various joints. RA most commonly affects the hands, wrists, and knees and displays in a bilateral and symmetrical pattern (i.e. both hands are affected). Risk factors include family history, sex (female), smoking, and hormonal factors.  

      Risk of Condition 

      ​​RA may involve one or multiple joints and may spread to other areas of the body including the eyes, mouth, lungs, and heart. RA can lead to tissue damage as well as chronic pain, unsteadiness, and deformity. Patients may experience acute worsening of their symptoms during a disease flare.  

      Medication 

      Role of Medication 

      The 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis recommends medications that may be used alone or in combination although DMARD naïve patients should start with DMARD monotherapy. The goal of treatment is to modify disease progression, achieve disease remission, and improve quality of life. Treatment will vary based on current disease activity. For patients in remission or with low disease activity for at least 6 months, it is reasonable to consider tapering of RA treatments while maintaining therapeutic dose of at least one agent. Choice of therapy should be based on multiple factors, including level of disease activity, comorbid conditions, concurrent medication, medication side effect profile, stage of therapy, insurance coverage, patient preference, and presence of adverse prognostic signs.  

      Rheumatoid Arthritis Medication Classes  

      • Drug Class: Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs)  
        • Medication Name:
          • Methotrexate (MTX)  
          • Leflunomide (LEF) 
          • Sulfasalazine (SSZ)  
          • Hydroxychloroquine (HCQ)  
      • Drug Class: Biologic Disease-Modifying Antirheumatic Drugs (bDMARDs)
        • Tumor Necrosis Factor Inhibitor (TNFi) Biologics 
          • Medication Name:
            • Adalimumab (Humira)  
            • Etanercept (Enbrel)  
            • Golimumab (Simponi) 
            • Certolizumab (Cimzia)  
            • Infliximab (Remicade)  
        • non-Tumor Necrosis Factor Inhibitor (non-TNFi) Biologics
          • Medication Name:
            • Abatacept (Orencia)  
            • Rituximab (Rituxan) 
            • Tocilizumab (Actemra) 
      • Drug Class: Targeted Synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs)  
        • Janus Kinase (JAK) Inhibitor 
          • Medication Name:
            • Tofacitinib (Xeljanz) 
      • Drug Class: Glucocorticoids 
        • Medication Name:
          • Prednisone/Prednisolone 
          • Methylprednisolone 
          • Dexamethasone  

      Recommendations for Medication Initiation and Treatment Modification  

      Treatment Initiation 

      Initiation of treatment in DMARD-naïve patients with moderate-to-high disease activity

      • MTX monotherapy 
        • Strongly recommended over:
          • SSZ 
          • HCQ 
          • bDMARD 
          • tsDMARD monotherapy 
          • MTX + non-TNFi bDMARD 
          • MTX + tsDMARD 
        • Conditionally recommended over:
          • LEF 
          • Dual or triple csDMARD therapy 
          • MTX + TNFi bDMARD 
          • MTX + non-TNFi bDMARD 
          • MTX + tsDMARD 

      Initiation of treatment in patients treated with a csDMARD (but MTX-naïve) and with moderate-high disease activity 

      • MTX monotherapy
        • Conditionally recommended over:
          • MTX + bDMARD 
          • MTX + tsDMARD 

      Initiation of treatment in DMARD-Naïve patients with low disease activity 

      • csDMARD monotherapy
        • HCQ conditionally recommended over other csDMARDs 
        • SSZ conditionally recommended over MTX 
        • MTX conditionally recommended over leflunomide 

      Initiation of csDMARD +/- Glucocorticoids in DMARD-naïve patients with moderate-to-high disease activity 

      • Conditionally recommend initiating csDMARDs without short-term (< 3 months) glucocorticoids  
      • Strongly recommend initiating csDMARDs without long-term (> 3 months) glucocorticoids

       

      Treatment Modification 

      Patients taking maximally tolerated MTX not at target 

      • Add a bDMARD or tsDMARD 
        • Conditionally recommended over adding SSZ or HCQ 

      Patients taking a bDMARD or tsDMARD 

      • Add a bDMARD or tsDMARD of a different class  
        • Conditionally recommended over switching to a bDMARD or tsDMARD of the same class

      Patients taking a glucocorticoid  

      • Add or switch to DMARDs  
        • Conditionally recommended over continuing glucocorticoids  
        • Conditionally recommended over the use of intra-articular (IA) glucocorticoids alone

      Adherence 

      Medication adherence is an essential component of treating RA. Patients should be informed that it may take up to 4 to 6 weeks for some modifications to take effect and 3 to 6 months to achieve full benefit. Discuss barriers to adherence and provide appropriate solutions. You may use the DRAW tool within the Worksheets & Forms category in this Knowledge Base.

      Administration 

      Methotrexate: MTX should be taken once weekly along with folic acid supplementation.  

      Glucocorticoids: Patient’s should be advised to avoid taking glucocorticoids too close to bedtime.  

      Injectables: For patients taking an injectable medication, it is important to provide education on appropriate injection technique. It may be useful to refer to the package insert or manufacturer website for best practices on administration of these medications.  

      Monitoring 

      Follow-up should occur on a regular basis for evaluation and monitoring. Follow-up should include clinical and laboratory assessment of disease activity and screening for drug toxicities.  

      Lifestyle Education  

      Lifestyle changes can play an important role in rheumatoid arthritis management. Discussion points may include: 

      • Encourage the patient to engage in routine physical activity if able. 
      • If appropriate, educate the patient about the benefit of occupational and/or physical therapy programs 

      Additional Points 

      Some DMARDs (e.g. MTX, LEF) are contraindicated in pregnant females or those who may become pregnant. If pregnancy occurs during treatment, these DMARDs should be discontinued immediately. In addition, alternative agents may have limited data available data in pregnancy and therefore patients should be advised to discuss risk versus benefit with their provider.  

      Given the immunosuppressive nature of RA treatments, immunizations should be considered prior to initiation of therapy whenever possible. The Centers for Disease Control (CDC) acknowledge guidance on immunization recommendations in immunocompromised patients based on planned immunosuppression, low-level immunosuppression, and high-level immunosuppression.  

       

       

      Resources 

      1. ACIP altered immunocompetence guidelines for immunizations. Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html.
      2. Rheumatoid arthritis guideline. American College of Rheumatology. https://rheumatology.org/rheumatoid-arthritis-guideline#2021-ra-guideline.