Module 2: Learning Objectives

• Pathophysiology of RA

  autoimmune condition where the body attacks the synovial and connective tissue causing inflammation.

  Chronic inflammation leads to growth of pannus which leads to loss of bone and cartilage.
• Clinical presentation of RA

  symmetrical joint pain and stiffness (especially early in the morning) for > 6 weeks. May also have fatigue, weakness, low-grade fever, appetite decrease, joint tenderness with warmth and swelling over affected joints, and/or rheumatoid nodules may develop.
• Goals of Therapy of RA 


  a patient assessment of global disease activity (PtGA) </= 2.
• Hydroxychloroquine admin, AE, efficacy, monitoring, CI, and DDIs?

  • Administration: oral
  • AE: NVD, stomach cramps, skin/allergic reactions, headaches, dizziness, myopathy, and ocular toxicity
  • Efficacy: better than placebo, worse then other DMARDs
  • Monitoring: ocular toxicity
  • CI: pre-existing retinopathy
  • DDIs: high risk QT prolongation
• sulfasalazine (pro-drug) admin, AE, efficacy, monitoring, CI, and DDIs?

  • Administration: oral
  • AE: headache, photosensitivity, NVD, and hematological abnormalities
  • efficacy: better than placebo, worse then other DMARDs - not for monotherapy
  • monitoring: CBCs, LFTs, and creatinine
  • CI: hypersensitivity to salicylates or sulfonamides, asthma ppted by ASA or NSAIDs, severe renal or hepatic impairment, and existing gastric or duodenal ulcer
  • DDIs: additive nausea with mtx, possible issue with warfarin
• methotrexate admin, AE, efficacy, monitoring, CI, and DDIs

  • Administration: oral
  • AE: N/V, fatigue, stomatitis, photosensitivity, hair loss, skin itching, burning, rash, hepatotoxicity, hematological abnormalities, pulmonary toxicity, reversible sterility in men, and infection increase
  • efficacy: healing of bone may occur
  • monitoring: CBCs, LFTs, creatinine, chest x-ray
  • CI: severe hepatic impairment, current hematological abnormalities, and pregnancy/breastfeeding
  • DDIs: trimethoprim and live vaccines
• Leflunomide admin, AE, efficacy, monitoring, CI, and DDIs? 


  • administration: oral
  • AE: N/D, rash, hypertension, reversible alopecia, hepatotoxicity, significant weight loss, and infection increase
  • efficacy: bone healing may occur
  • monitoring: CBCs, LFTs, creatinine
  • CI: moderate-severe renal or hepatic impairment, current hematological abnormalities, serious infections, pregnancy, and breastfeeding
  • DDIs: bile acid sequestrants, additive immunosuppression, and live vaccines
• Concerns for all biologics

  • Nausea, diarrhea, headache, and malaise
  • injection site reactions
  • infection rate increase
  • neutropenia
  • malignant disease - lymphoma and skin cancer
  • antibody development
• TNF-alpha inhibitors

  • adalimumab
  • certolizumab
  • etanercept
  • golimumab
  • infliximab
• Routes for TNF-alpha inhibitors

  • adalimumab (SC)
  • certolizumab (SC)
  • etanercept (SC)
  • golimumab (IV or SC)
  • infliximab (IV)
• TNF-alpha inhibitors AEs, efficacy, monitoring, CI, and DDIs

  • AE: liver enzyme elevations, HF, cutaneous reactions, autoimmune diseases, and seizure risk
  • efficacy: ACR50 of 40%, combo with mtx more effective. Stop/slows radiographic progression.
  • monitoring: TB, HIV, Hep B/C screening, CBCs, LFTs, signs of infection, and ensure vaccination
  • CI: active severe infections + moderate to severe HF
  • DDIs: live vaccines + additive immunosuppression
• IL-1 and IL-6 inhibitors

  • Anakinra (IL-1 - SC)
  • Tocilizumab (IL-6 - IV)
  • Sarilumab (IL-6 - SC)
• T-cell co-stimulation inhibitors

  abatacept
• T-cell co-stimulation inhibitor admin, AEs, efficacy, monitoring, CI, and DDIs


  • admin: LD IV (optional) then SC
  • AE: similar to TNF-alpha inhibitor, COPD exacerbations (!!), hypertension, and blood glucose increase
  • efficacy: 41% achieved ACR50
  • monitoring: signs and sxs of infection, TB and hepatitis screening, CBCs, creatinine, blood pressure + glucose
  • CI: COPD
• B-cell depletor

  rituximab
• B-cell depletor admin, AE, efficacy, and monitoring

  • admin: IV infusion given 2 weeks apart - must pretreat with methylprednisolone, acet, and diphenhydramine
  • AE: infusion site reactions, serious infection rate (increased with repeat courses), hypertension, GI perforation, blood glucose increase, mucocutaneous reactions, and antibody formation
  • efficacy: ACR50 of 43%, no halt in radiographic progression
  • monitoring: baseline CBC, LFT, creatinine, TB, hepatitis B/C screening
• Important differences:

  • liver injury: all except abatacept (T-cell)
  • HF: TNF-alpha inhibitors
  • COPD exacerbation: abatacept
  • GI perforation: IL-6
  • hypertension: IL-6
  • increase in lipids: IL-6
  • glucose changes: abatacept
  • Seizures: TNF-alpha inhibitors
• Janus Kinase inhibitors

  Tofacitinib

  Baricitinib

  Upadacitinib
• Janus kinase inhibitor admin, AE, efficacy, monitoring, CI, and DDI

  • admin: oral
  • AE: similar to TNF-alpha inhibitors and other biologics - hypertension, infections, cytopenia, hepatotoxicity, bradycardia, and GI perforation
  • efficacy: combined with mtx ACR50 of 46%, monotherapy of 38%
  • monitoring: latent TB testing, lipid profile, CBCs, LFTs, pregnancy, lactation
  • CI: severe infections
  • DDI: live vaccines, additive immunosuppression
• Corticosteroids for RA admin, AE, efficacy, monitoring, CI, and DDI

  • Admin: oral preferred over intra-articular injections
  • AE: normal
  • efficacy: reduces joint tenderness + pain, subjective symptomatic improvement
  • monitoring: cataracts, dyslipidemia, hyperglycemia, osteoporosis, and weight gain
• Gout pathophysiology


  results from deposition of monosodium urate in synovial fluids, tissues, and the kidney.
• Gout presentation 


  intense pain, redness, heat, swelling, more often at night.
• Gout clinical phases

  1. asymptomatic gout
  2. acute gouty arthritis
  3. intercritical gout
  4. chronic tophaceous gout
• NSAIDs for gout

  • first line choice
  • use high doses for first 2-3 days, then lowest effective dose for 2-3 days
  • any NSAID good but: naproxen, ibuprofen, ketoprofen, indomethacin, and celecoxib
  • more ADR then corticosteroids but less than colchicine
• Corticosteroids for gout

  prednisone commonly used, can be in any dosage form - intraarticular is better for gout then RA and is a very good option if they have access to an experienced HCP. limit to 4 injections/per year/joint. Caution use if systemic symptoms are present, if diabetic, and if excessive previous steroid use.