What is the recommended second-line therapy for a patient with osteoarthritis (OA) of the knee who did not respond to first-line therapy, according to European Alliance of Associations for Rheumatology (EULAR) guidelines?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 13, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

The recommended second-line therapy for a patient with osteoarthritis (OA) of the knee who did not respond to first-line therapy, according to European Alliance of Associations for Rheumatology (EULAR) guidelines, is NSAIDs with gastroprotection. This is based on the evidence that NSAIDs are more efficacious than paracetamol in the management of knee OA, although they may have increased gastrointestinal side effects 1. The EULAR guidelines suggest that NSAIDs should be considered in patients unresponsive to paracetamol, and that non-selective NSAIDs and effective gastroprotective agents, or selective COX 2 inhibitors should be used in patients with an increased gastrointestinal risk 1. Some key points to consider when prescribing NSAIDs include:

  • Using the lowest effective dose for the shortest duration possible to minimize side effects
  • Monitoring for gastrointestinal, cardiovascular, and renal side effects, particularly in elderly patients or those with comorbidities
  • Considering gastroprotective agents like proton pump inhibitors for patients at high risk of gastrointestinal complications
  • Typical oral NSAIDs include ibuprofen (400-800mg three times daily), naproxen (250-500mg twice daily), or celecoxib (100-200mg daily) Intra-articular corticosteroid injections can also be considered for patients who cannot take oral NSAIDs due to contraindications or who remain symptomatic despite them, especially if accompanied by effusion 1. However, the benefit of intra-articular corticosteroid injections may be relatively short-lived, typically lasting 3-4 weeks 1. It is essential to tailor the treatment of knee OA according to individual patient factors, including knee risk factors, general risk factors, level of pain intensity and disability, signs of inflammation, and location and degree of structural damage 1.

From the Research

Second-Line Therapy for Osteoarthritis of the Knee

According to the European Alliance of Associations for Rheumatology (EULAR) guidelines, the recommended second-line therapy for a patient with osteoarthritis (OA) of the knee who did not respond to first-line therapy is:

  • NSAIDs with gastroprotection 2, 3

Rationale

The use of NSAIDs with gastroprotection is recommended as second-line therapy due to their efficacy in relieving pain and improving function in OA patients, while minimizing the risk of gastrointestinal adverse events 2, 3.

Alternative Options

Other options, such as intra-articular steroids 4, 5 and intra-articular non-steroidal anti-inflammatory drug injections 6, may also be considered as second-line therapy, but the evidence suggests that NSAIDs with gastroprotection are a preferred option.

Key Points

  • NSAIDs with gastroprotection are a recommended second-line therapy for OA of the knee 2, 3
  • Intra-articular steroids and intra-articular non-steroidal anti-inflammatory drug injections are alternative options 4, 5, 6
  • The choice of second-line therapy should be based on individual patient needs and medical history 3, 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.