Injection Therapy for Osteoarthritis (OA) of the Knee

The references listed below are used in this DynaMed topic primarily to support background information and for guidance where evidence summaries are not felt to be necessary. Most references are incorporated within the text along with the evidence summaries.

1. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken) 2020 Feb;72(2):149-162.
2. Testa G, Giardina SMC, Culmone A, et al. Intra-Articular Injections in Knee Osteoarthritis: A Review of Literature. J Funct Morphol Kinesiol. 2021 Feb 3;6(1).
3. Wehling P, Moser C, Maixner W. How does surgery compare with advanced intra-articular therapies in knee osteoarthritis: current thoughts. Ther Adv Musculoskelet Dis. 2016 Jun;8(3):72-85.
4. Ayhan E, Kesmezacar H, Akgun I. Intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis. World J Orthop. 2014 Jul 18;5(3):351-61.

• American Academy of Orthopaedic Surgeons (AAOS) grading system for recommendations:
  • Strong:
    • Strong or Moderate strength of evidence
    • Evidence from ≥ 2 “High” quality studies with consistent findings to recommend for or against intervention, or recommendation upgraded from Moderate using evidence to decision framework
  • Moderate:
    • Strong, Moderate, or Limited strength of evidence
    • Evidence from ≥ 2 “Moderate” quality studies with consistent findings, or evidence from single “High” quality study to recommend for or against intervention, or recommendation upgraded or downgraded from Limited or Strong using evidence to decision framework
  • Limited:
    • Limited or Moderate strength of evidence
    • Evidence from ≥ 1 “Low” quality studies with consistent findings OR evidence from single "Moderate" quality study to recommend for or against intervention, or recommendation downgraded from Moderate using evidence to decision framework
  • Consensus:
    • No evidence
    • No supporting evidence, or higher quality evidence was downgraded due to major concerns addressed within evidence to decision framework. In absence of reliable evidence, guideline work group is making recommendation based on clinical opinion
  • Reference - AAOS guideline on management of osteoarthritis of the knee [nonarthroplasty] (AAOS 2021 Aug 30 PDF)
• American College of Rheumatology/Arthritis Foundation (ACR/AF) grading system for recommendations:
  • Strength of recommendation:
    • Strong - voting panel confident that desirable effects of following recommendation outweigh potential undesirable effects (or vice versa)
    • Conditional - quality of evidence proved low or very low and/or balance of benefits vs. Harms and burdens was sufficiently close that shared decision-making between the patient and the clinician would be particularly important
  • Quality of evidence:
    • High quality - further research is very unlikely to change confidence in estimate of effect
    • Moderate quality - further research is likely to have an important impact on confidence in estimate of effect and may change estimate
    • Low quality - further research is very likely to have an important impact on confidence in estimate of effect and likely to change estimate
    • Very-low quality - any estimate of effect is very uncertain
  • Reference - ACR/AF guideline on management of osteoarthritis of the hand, hip, and knee (Arthritis Care Res (Hoboken) 2020 Feb;72(2):149)
• Osteoarthritis Research Society International (OARSI) grading system for recommendations:
  • Strength of recommendation:
    • Strong recommendation - confident that benefits of particular intervention outweigh harms, or that harms outweigh benefits
    • Conditional recommendation - intervention carries risk that could potentially outweigh benefits; higher degree of uncertainty in values and preferences
  • Level of evidence:
    • Level 1A - ≥ 75% in favor; > 50% strong recommendation
    • Level 1B - ≥ 75% in favor; > 50% conditional recommendation
    • Level 2 - 60%-74% in favor; conditional recommendation by default
    • Level 3 - 41%-59% in favor; conditional recommendation by default
    • Level 4A - ≥ 75% against; > 50% conditional recommendation
    • Level 4B - 60%-74% against; conditional recommendation by default
    • Level 5 - ≥ 75% against; > 50% strong recommendation
  • Core treatments:
    • Voting panel members selected Core treatments (treatments deemed appropriate for use by majority of patients in nearly any scenario and deemed safe in conjunction with first line and second line treatments) from a prespecified list of candidates
    • Non-Core treatments designated to Level 1A, 1B, 2, 3, 4A, 4B, or 5
  • Nonrecommended treatments:
    • Any interventions graded as Level 3, Level 4A, or Level 4B were recommended against
    • Interventions graded as Level 5 were strongly recommended against, indicating that there are no clinical scenarios in which these treatments would be deemed appropriate in patients with OA
  • Good Clinical Practice Statements:
    • Reviewed and adopted with consensus of both Core expert panel members and voting panel members
    • Intended to act as qualifiers for existing treatment recommendations (not to act as stand-alone recommendations)
  • PubMed31278997Osteoarthritis and cartilageOsteoarthritis Cartilage2019110127111578-15891578 Reference - OARSI guideline on non-surgical management of knee, hip, and polyarticular osteoarthritis (Osteoarthritis Cartilage 2019 Nov;27(11):1578)
• European League Against Rheumatism (EULAR) grading system for recommendations:
  • Strength of recommendations:
    • Grade A - directly based on category 1 evidence
    • Grade B - directly based on category 2 evidence or extrapolated recommendations from category 1 evidence
    • Grade C - directly based on category 3 evidence or extrapolated recommendations from category 1 or 2 evidence
    • Grade D - directly based on category 4 evidence or extrapolated recommendations from category 2 or 3 evidence
  • Level of evidence:
    • Category 1A - meta-analysis of randomized controlled trials
    • Category 1B - ≥ 1 randomized controlled trial
    • Category 2A - ≥ 1 controlled study without randomization
    • Category 2B - ≥ 1 type of quasi-experimental study
    • Category 3 - descriptive studies, such as comparative studies, correlation studies, or case-control studies
    • Category 4 - expert committee reports or opinions and/or clinical experience of respected authorities
  • Reference - EULAR recommendations on intra-articular therapies (Ann Rheum Dis 2021 Oct;80(10):1299)

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