1. 1.Minimize symptoms 

2. 2.Alleviate pain 

3. 3.Maintain joint function and range of motion 

4. 4.Prevent disease progression 

5. 5.Maximize medication efficacy, safety, and tolerance 

• •Rest – relieves stress on inflamed joints and helps with alleviation of pain – too much rest can be a bad thing 

• •Occupational and physical therapy – provides the patient with skills and exercises necessary to increase or maintain mobility 

• •Weight loss and surgery – weight reduction helps to alleviate inflamed joint stress.  Joint replacements are surgical options for patients for severe RA 

• •Need to evaluate patient-specific factors and select appropriate treatment to maximize care 

• •Aggressive treatment is defined as one or more disease-modifying antirheumatic drugs (DMARDs) at effective doses 

• •Delaying treatment will result in more destructive disease that is very difficult to delay or reverse to preserve joint function 

• •Specialty care by a rheumatologist may reduce the likelihood of disease progression and joint damage 

• •It is imperative that the initiation of one or more DMARDs occurs in all patients within the first 3 months of diagnosis to reduce joint erosion 

• •Starting combination therapy initially is referred to as the step-down approach 

• •Adding a second or third agent after an adequate trial of DMARD monotherapy is considered a step-up approach 

• •Most clinicians favor the “step-down” approach to slow or reverse the early articular damage as soon as possible 

The following medication classes are prescribed commonly for the treatment of RA:

1. • •Nonsteroidal anti-inflammatory drugs (NSAIDs) 

   • •Glucocorticoids 

   • •Nonbiologic DMARDs – csDMARDs – conventional DMARDs 

   • •Biologic DMARDs – bDMARDs 

   • •tsDMARDs – targeted synthetic DMARDs 

• •NSAIDs provide analgesic and anti-inflammatory benefits for joint pain and swelling 

• •DO NOT prevent joint damage or change the underlying disease 

• •Used for “bridge therapy” until the therapeutic effect of DMARD is observed 

• •Patients not responding to one NSAID, may respond to another 

• •NSAID use is associated with an increased risk of GI ulcers or hemorrhage, fluid retention, exacerbation of existing hypertension, and decreased renal function in certain patient populations 

• •Patients need periodic monitoring for GI bleeding and renal function 

• •Patients can take with food to minimize the risk of GI ulceration 

• •Patients requiring long-term NSAID use, may need concomitant proton pump inhibitor or misoprostol therapy to reduce the risk of NSAID-induced peptic ulcer 

• •Methotrexate is the nonbiologic DMARD of choice in RA because of its documented efficacy and safety profile when monitored appropriately 

• •Once-weekly!! Doses should be initiated within 3 months of diagnosis and increased steadily until the patient has symptomatic improvement or 20 mg/week is reached 

• •IM and SC administration once weekly available if patients experience severe GI adverse effects to the oral formulation 

• •Common side effects include nausea, vomiting, diarrhea, alopecia, and general malaise.  Elevation of liver transaminases (AST/ALT), renal toxicity, and thrombocytopenia or bone marrow suppression may occur 

• •Methotrexate should not be used in patients with transaminases more than twice the upper limit of normal, poor renal function (CrCl < 30 mL/min), a WBC < 3,000/mm3, or a platelet count < 50,000 

• •Methotrexate may be used in combination with other nonbiologic or biologic DMARDs 

• •Concomitant folic acid is given routinely to reduce the risk of folate-depleting reactions induced by methotrexate therapy (stomatitis, diarrhea, nausea, alopecia, myelosuppression, and elevations in liver function tests) 

• •Typically avoid in patients with pre-existing liver disease or for those who consume large amounts of alcohol  

• • •Discourage drinking all together
     

• •Teratogenic and abortifacient and can decrease fertility in both men and women – therapy should be stopped 3 months before conception 

• •Rare hypersensitivity pneumonitis can occur (1-2%) – especially in patients with prior lung disease 

• •Drug-drug interactions: Bactrim and trimethoprim interfere with folate metabolism and may increase bone marrow suppression, NSAIDs (decrease MTX renal excretion and could increase toxicity – although relative caution 

• •Exact MOA of these drugs is unknown, but both agents are well tolerated 

• •Both drugs are used for mainly mild disease 

• •Hydroxychloroquine is not associated with hepatic/renal toxicities or bone marrow suppression.  Ophthalmological examinations due to risk of macular damage and retinal toxicity.  Nausea, epigastric pain and QT prolongation 

• •Sulfasalazine can cause N/V, anorexia, bone marrow suppression, rash, photosensitivity, and elevated liver transaminases.  Don’t use with liver transaminases > 2 times ULN OR sulfa allergic patients 

• •Hydroxychloroquine 200 mg po bid, Sulfasalazine 500 mg po bid 

• •Leflunomide inhibits the T-lymphocyte response to various stimuli and halts the cell cycle 

• •Efficacy is similar to moderate doses of methotrexate and sulfasalazine 

• •Common side effects include diarrhea, rash, alopecia, headache, weight loss, and elevated transaminases 

• •DO NOT use in patients with transaminases > 2xULN, active TB, bacterial, herpes zoster, or life-threatening fungal infection, or in patients with WBC < 3000/mm3 or platelet < 50,000 

• •Pregnancy Category X.  Monitor liver transaminase, CBC, SCr 

• •100 mg loading dose for 3 days, followed by 10-20 mg once daily 

• •Etanercept – Enbrel 

• •Infliximab – Remicade, Avsola, Inflectra, Renflexis 

• •Adalimumab - Humira 

• •Golimumab – Simponi 

• •Certolizumab pegol - Cimzia 

• •Heart failure is a relative contraindication for anti-TNF agents 

• •Anti-TNF agents should not be resumed or continued in patients with serious infections – Screen for TB and have a (-) tuberculin-PPD skin test 

• •TNF inhibitors may predispose patient to an increase in cancer risk (lymphoma/skin cancer) 

• •Local injection-site reactions are common – infusion related reactions 

• •Abatacept – Orencia 

• •Interferes with T-cell signaling, ultimately blocking T-cell activation and leading to anergy, or lack or response to antigen 

• •Shows some response in patients refractory to methotrexate and anti-TNF therapy 

• •Adverse reactions limited to nausea, headache, infections, and infusion-related reactions 

• •Used as monotherapy or combination with nonbiologic DMARDs 

• •Initial infusion at 0, 2 & 4 weeks - 125 mg sc once/week 

• •Rituximab – Rituxan (Riabni, Ruxience, Truxima) 

• •Genetically engineered chimeric anti-CD20 monoclonal antibody that causes B-lymphocyte depletion 

• •Exact role is not clearly defined, but indicated for patients with moderate to severe active RA and a history of inadequate response to one or more TNF antagonists 

• •Black-box warning of fatal infusion reactions and severe mucocutaneous reactions – outside of RA trials 

• •Interleukin-6 is produced in high amounts in patients with RA – Tocilizumab selectively and completely antagonizes IL-6 receptors 

• •Tocilizumab – Actemra or Sarilumab - Kevzara 

• •Shows some response to patients not responding to methotrexate or other TNF antagonists 

• •ADRs include nasopharyngitis, infection, elevated LFTs and cholesterol 

• •IV infusion every 4 weeks OR SQ at weekly or biweekly intervals 

• •Tofacitinib (Xeljanz) 

• • •First oral Janus kinase (JAK) inhibitor indicated for the treatment of RA 

• • •5mg PO BID 

• • •For moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to MTX 

• • •May be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs – not recommended for combination use with biologic DMARDs 

• • •Serious adverse effects: increased infection and malignancy risk, neutropenia, anemia, increased LFTs (avoid in hepatic impairment) – use with caution in patients at high risk of GI perforation 

• •Baricitinib – Olumiant – 2 mg po once daily 

• •Upadacitinib – Rinvoq – 15 mg po once daily 

• •Tofacitinib and Upadacitinib are metabolized by CYP3A4 

• •Potential signal of increased thrombotic risk 

• •Many agents used in RA are known teratogens 

• •Women desiring motherhood must consult with their physicians to carefully plan for pregnancy 

• •Low-dose corticosteroids generally are safe and effective 

• •Methotrexate is category X 

• •Considerations in male patients 

• •Fraenkel, Liana, Joan M. Bathon, Bryant R. England, E. William St. Clair, Thurayya Arayssi, Kristine Carandang, Kevin D. Deane et al. "2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis." Arthritis & Rheumatology 73, no. 7 (2021): 1108-1123. 

• •Shams, Shahin, Joseph M. Martinez, John RD Dawson, Juan Flores, Marina Gabriel, Gustavo Garcia, Amanda Guevara et al. "The therapeutic landscape of rheumatoid arthritis: current state and future directions." Frontiers in Pharmacology 12 (2021): 680043. 

• •Tan, Yvonne, and Maya H. Buch. "'Difficult to treat'rheumatoid arthritis: current position and considerations for next steps." RMD open 8, no. 2 (2022): e002387.