Arthralgias and Arthritis

Grading Toxicity

Arthralgia

Definition:  A disorder characterized by a sensation of marked discomfort in a joint

  • Mild pain
  • Moderate pain; limiting instrumental ADL
  • Severe pain; limiting self-care ADL

Arthritis

Definition: A disorder characterized by inflammation involving a joint

  • Mild pain with inflammation, erythema, or joint swelling
  • Moderate pain associated with signs of inflammation, erythema, or joint swelling; limiting instrumental ADL
  • Severe pain associated with signs of inflammation, erythema, or joint swelling; irreversible joint damage; disabling; limiting self-care ADL

Management

Overall Strategy:

  • Assess for other etiologies, such as lytic or osseous metastasis
  • Early intervention to maintain or improve physical function and impact on QOL; symptom control through the treatment of inflammation and pain is often achieved with NSAIDs, corticosteroids, and other adjunct therapies
  • No known interventions
  • Anticipate immunotherapy to continue
  • Encourage physical activity
    • 30 minutes of low-to-moderate–intensity physical activity 5 days per week can improve physical conditioning, sleep, and decreases pain perception
    • For physically inactive patients, advise supervised exercise, resistance training
    • Other: yoga, tai chi, Qigong, Pilates, aquatic exercise, focused dance program
  • Anticipate use of analgesia
    • Low-dose NSAIDs
      • Topical: diclofenac (gel or patch). Best for localized, limited, superficial joint inflammation or for use in patients who cannot tolerate oral NSAIDs
      • Oral: ibuprofen, naproxen, celecoxib
        • Anticipatory guidance on proper administration
  • Assess patient and family understanding of recommendations and rationale
    • Identify barriers to adherence

If symptoms do not improve in 46 weeks, escalate to next level of therapy

  • Ipilimumab to be withheld for any Grade 2 event (until Grade 0/1) and discontinued for events persisting ≥6 weeks or inability to reduce steroid dosage to 7.5 mg prednisone or equivalent per day
  • Dose of pembrolizumab or nivolumab to be held as to not make symptoms worse
  • Pembrolizumab or nivolumab to be discontinued for Grade 2 events persisting ≥12 weeks
  • Continue to encourage physical activity
  • Anticipate use of analgesia
    • NSAIDs
      • Oral: ibuprofen, naproxen, celecoxib
        • Anticipatory guidance on proper administration
  • Anticipate referral to rheumatology for collaborative management and consideration of adjunct treatment
  • Anticipate pre-visit assessment: CBC, ESR, CRP, BUN/CR & aminotransferases, ANA, RF
    • Intraarticular steroids to be used for significant symptomatic joint(s)
    • Low-dose corticosteroids (0.5 –1 mg/kg/day) to be used
      • Anticipatory guidance on proper administration
      • Duration of corticosteroid therapy is usually limited, lasting for about 4–6 weeks, with possible resolution of symptoms within weeks to months of treatment
  • Assess patient & family understanding of toxicity, rationale for treatment hold (if applicable)
    • Identify barriers to adherence

If symptoms do not improve in 46 weeks, escalate to next level of therapy

  • Pembrolizumab or nivolumab to be withheld for first-occurrence Grade 3/4 event and discontinued if:
    • Grade 3/4 event recurs
    • Persists ≥12 weeks
  • Ipilimumab to be discontinued for any Grade 3/4 event.
  • High-dose steroids to be used (1-1.5 mg/kg) daily; [rapid effect within days]
    • Anticipatory guidance on proper administration
    • Onset of action is rapid, typically within days
  • Anticipate referral to rheumatology for collaborative management and consideration of adjunct treatment
    • Non-biologic agents (more likely to be recommended)
      • Conventional synthetic DMARDs (csDMARDs), which have a delayed effect and take weeks to work:
        • Methotrexate
        • Sulfasalazine*
        • Hydroxychloroquine
        • Leflunomide
    • Biologic agents (less likely to be recommended)
      • Biologic DMARDs (bDMARDs)
      • TNF inhibitors
        • Infliximab
        • Etanercept
        • Adalimumab
        • Golimumab
        • Certolizumab pegol
      • Anti B-cell agents (CD-20 blocking)
        • Rituximab
    • Agents NOT advised
      • Interleukin (IL)-6 receptor blocking agent (tocilizumab) and JAK inhibitors (tofacitinib) due to risk of colonic perforation
      • T cell co-stimulation inhibitor (abatacept) as it directly opposes the mechanism of checkpoint blockade agents
  • Assess patient & family understanding of toxicity and rationale for treatment discontinuation
  • Identify barriers to adherence, specifically compliance with medication, physical activity

*Sulfasalazine is associated with rash; do not use in patients with history of or current treatment-related dermatitis

Nursing Implementation:

  • Identify high-risk individuals and those with underlying autoimmune dysfunction
  • Educate patients that arthralgias and arthritis are the most commonly reported rheumatic and musculoskeletal irAEs with checkpoint inhibitors
  • Arthritis-like symptoms can range from mild (managed well with NSAIDs and low-dose corticosteroids) to severe and erosive (requiring multiple immunosuppressant medications)
  • Anticipate that the steroid requirements to manage arthralgias can be much higher (i.e., up to 1.5 mg/kg/day) than typically required to manage “classic” inflammatory arthritis
  • Educate patients that symptoms can persist beyond treatment completion or discontinuation

RED FLAGS:

  • Risk of fall due to mobility issue