BJ is a 28-year-old female who presents to your pharmacotherapy clinic with complaints of joint swelling and tenderness in both hands. She has been using acetaminophen, but she states that it hasn’t been effective. She reports that her symptoms have progressed over the past two weeks and include numbness and tingling in both hands, fatigue, and general malaise. She had tried ibuprofen consistently for several weeks a month ago with no help as well.  Upon completion of laboratory tests, imaging studies, and a physical exam, the patient is diagnosed with rheumatoid arthritis with high disease activity. The rheumatologist wishes to begin treatment. 

PMH: hypertension, dyslipidemia, pulmonary embolism 2 months ago  

Meds: Zestril 20mg daily, Errin 0.35mg daily, acetaminophen 500mg BID prn, Pradaxa 150mg BID, Crestor 20mg daily 

Allergies: Sulfa (anaphylaxis) 

Social history: nonsmoker, no alcohol consumption 

Pertinent labs: 

• Na: 137, K: 3.6, Cl: 97, BUN: 15, Scr 0.8mg/dL, CrCl 98ml/min 
• Vitals: BP: 130/76, HR 96, RR 12, Temp 98.6 F 
• Weight – 86kg Height – 67 inches  
• (+) RF (Rheumatoid Factor) 
• X-ray shows joint space narrowing in affected joints 
• (-) hCG (human chorionic gonadotropin hormone) 

Which of the following would be appropriate options to initially manage this patient's RA? Select all that apply. 

A. Azulfidine

B. Rheumatrex

C. Otrexup

D. Rinvoq

E. Olumiant

Brand/Generics covered: Zestril (lisinopril), Errin (norethindrone), Crestor (rosuvastatin), Pradaxa (dabigatran), Azulfidine (sulfasalazine), Rheumatrex (methotrexate), Otrexup (methotrexate), Rinvoq (upadacitinib), and Olumiant (baricitinib) 

Rationale with explanation: 

Correct answers: B, C

Answer choice A is incorrect. Azulfidine (sulfasalazine) is a type of drug known as a disease-modifying anti-rheumatic drug (DMARD) and has been shown to prevent disease progression and joint destruction. Azulfidine is structurally composed of sulfapyridine, a sulfonamide. Therefore, the use of Azulfidine would be inappropriate in this patient due to the severe sulfa allergy documented. 

Answer choice B is correct. According to the 2021 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis, methotrexate is strongly recommended over hydroxychloroquine or sulfasalazine, a biologic DMARD or targeted synthetic DMARD, and a combination of methotrexate plus a non-TNF inhibitor biologic DMARD or targeted synthetic DMARD for DMARD- naïve patients with moderate-to-high disease activity. Additionally, BJ does not present with any contraindications to methotrexate. See precautious here. 

Understanding the risks and side effects associated with methotrexate is important for patients to undergoing therapy. For example, methotrexate is teratogenic. BJ is currently taking Errin and it would be important to counsel her on the importance of continuing her birth control regimen. BJ is likely receiving a progestin only agent due to recent clot which can be associated with estrogen therapy. Other side effects associated with methotrexate include mucositis, GI ulcers, alopecia, nausea, photosensitivity, hepatotoxicity, and myelosuppression. As a result, laboratory tests such as LFTs, CBC, and SCr should be closely monitored in patients undergoing methotrexate therapy. 

Answer choice C is correct. Otrexup is a branded product of subcutaneous methotrexate and is a viable option for treating RA. While there are some data suggesting superior outcomes for SC methotrexate, the oral dosage form due to good evidence and ease of administration is also an excellent first-line option. 

Answer choices D and E are incorrect. Rinvoq (upadacitinib) and Olumiant (baricitinib) are both Janus kinase (JAK) inhibitors that work by preventing cytokine and growth factor signaling. Rinvoq and Olumiant both have a black box warning on their label cautioning patients of the potential risk of serious infections, malignancy, and thrombosis. The use of these drugs should be avoided in patients who may be at increased risk for thrombosis. BJ’s history of PE puts her at increased risk for thrombosis and JAK inhibitors would be inappropriate.  In addition, these would not be first-line options over either oral or subcutaneous methotrexate. 

NAPLEX Competencies Covered: NAPLEX Competencies Covered: Area 1 (Obtain, Interpret, or Assess Data, Medical or Patient Information), 1.5 Signs and symptoms of medical conditions, health physiology, etiology of diseases or pathophysiology; Area 2 (Identify Drug Characteristics), 2.1 Pharmacology, mechanism of action, or therapeutic class; 2.2 Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied; Area 3 (Develop or Manage Treatment Plans), drug dosing or dosing adjustments; duration of therapy; 3.6 drug contraindications, allergies, or precautions.  

References: 

American College of Rheumatology Guidelines 

Methotrexate Package Insert 

Baricitinib Package Insert 

Otrexup Package Insert

Good luck everyone!

Dr. B