Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis

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McAlindon TE, et al. "Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial". JAMA. 2017. 317(19):1967-1975.
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Clinical Question

Among patients with knee osteoarthritis (OA) is intra-articular triamcinolone effective and safe to reduce pain and maintain cartilage volume?

Bottom Line

Intra-articular triamcinolone therapy for two years has greater cartilage loss as compared to intra-articular saline although both resulted in no relief of pain.

Major Points

The study looked at the use of intra-articular injection triamcinolone acetonide on progression of cartilage loss and knee pain. Previous studies with intra-articular corticosteroid injections lacked proper imaging (radiography) or showed a possibility of adverse effects. This, in addition to the risk of anti-anabolic effects prompted further studies.(1)

The study consisted of 140 participants split into two groups in a 2-year randomized double-blind clinical trial of intra-articular triamcinolone administered every 3 months vs. saline (placebo) for symptomatic knee OA with ultrasonic evidence of synovitis. Outcomes measured were cartilage loss, articular structure damage, pain, and physical function. There was no significant difference in: progression of cartilage denudation, bone marrow lesion, effusion volume, trabecular morphology, subchondral tibia/hip/bone mineral density, knee pain, secondary patient reported or objective clinical end points, or serious adverse events. The rate of cartilage loss was greater in the triamcinolone group for cartilage thickness and for secondary cartilage damage index. There were more adverse events in the saline group (63 vs 52 patients).

The study was measuring pain improvement among other outcomes, but did not measure pain within the first 4 weeks after each injection. Also, patients discontinued their current medications so any added benefit from the injections could not be measured. Therefore, the study had low validity with contradicting results in terms of pain improvement. The results of this study are not useful for determining the benefits and risks of using saline or triamcinolone injections for treatment of osteoarthritis of the knee.

Guidelines

2018 American College of Rheumatology Guideline for the Pharmacologic and Non-Pharmacologic Management of Osteoarthritis of the Hand, Hip and Knee (final publication anticipated in 2018).2

Table 4 in the guidelines recommend the following Pharmacologic and Nonpharmacologic options for the initial management of knee OA:

Pharmacological Recommendations:

  • First Line:
    • Acetaminophen
    • Oral NSAIDs
    • Topical NSAIDs
  • Second/Last Line:
    • Tramadol
    • Intra-articular corticosteroid injections

Non Pharmacological Recommendations:

  • Cardiovascular (aerobic) and/or resistance land-based exercise
  • Aquatic exercise
  • Lose weight (if overweight)
  • Self-management programs
  • Manual therapy with supervised exercise
  • Psychosocial interventions
  • Medially directed patellar taping
  • Medially wedged insoles (with lateral compartment OA only)
  • Laterally wedged subtalar strapped insoles (with medial compartment OA only)
  • Receive walking aids, as needed
  • Participate in tai chi programs

Design

  • Trial type: 2 year, randomized, placebo-controlled, double-blind trial
  • N=140
  • Experimental arm: (n=70)
  • Standard: (n=70)
  • Setting: Tufts Medical Center
  • Enrollment: February 11, 2013-January 1, 2015
  • Mean follow-up: 2 Years
  • Analysis: main analysis type: Intention to treat analysis
  • Primary outcome: Change in knee cartilage volume in the index compartment with coprimary outcome assessing change in pain

Population

Inclusion Criteria

  • Age of 45 years or older
  • Presence of knee osteoarthritis (defined by the American College of Rheumatology classification criteria)
  • Knee pain score ≥2 but ≤8 on the weight-bearing [WOMAC]17 pain subscale (range 0-12)
  • Discontinuation of analgesics for at least 48 hours before evaluation
  • Ultrasonographic evidence of effusion synovitis in the study knee (defined pouch depth larger than 2 mm)

Exclusion Criteria

  • Disorders affecting the study joint, these include systemic inflammatory joint disease,prior sepsis, osteonecrosis; chronic or recent use of oral corticosteroids, doxycycline, indomethacin, glucosamine, or chondroitin; recent (<3 months) intraarticular corticosteroids or hyaluronic acid; serious medical conditions (like uncontrolled diabetes, HIV infection, or hypertension) that could be contraindications to participation; and any contraindication to undergoing an MRI scan.

Baseline Characteristics

Triamcinolone (n=70)

  • Demographics: Age 59.1 years, female 37%
  • Baseline health data: BMI: 30.8, White: 47%
    • Varus or valgus malalignment: 53%
    • Synovial pouch depth: 4.2 mm
    • KL score, No. (%)
      • 2: 29
      • 3: 41
    • Clinical VAS pain score: 38.4

(Values range from 0-100, 0 indicating no pain and 100 extreme pain)

    • Womac Score:
      • Pain: 8.2
      • Function: 28.3
      • Stiffness: 3.7

(Scores for WOMAC, pain subscale of 0-12)

    • 20-m Walk: 19.8 sec.
    • Chair Stand: 18.3 sec.
    • SF-36 score:
      • Physical: 36.7
      • Mental: 52.6

(The 36-Item Short Form Health Survey (SF-36) scores range from 0 to 100, with higher scores representing better health status)

    • Hemoglobin A mean: 6.0 %
    • C-reactive protein mean (mg/L)(log): 0.6

Interventions

Triamcinolone 1 mL ( 40 mg/mL) was used for injection. Sodium chloride (0.9%) 1 ml injection was compared.

  • Both groups treated every 12 weeks for 2 years

Outcomes

Primary Outcomes

The use of intra-articular triamcinolone resulted in a greater cartilage volume loss than saline for a mean change in index compartment cartilage thickness of -0.21mm vs -0.10mm (between-group difference, -0.11mm; 95% CI, -0.20mm to -0.03mm) (p value=0.1). There was no difference in pain between the groups (−1.2 vs −1.9; between-group difference, −0.6; 95% CI, −1.6 to 0.3) (p value = 0.17).

Secondary Outcomes

Secondary outcomes included function which was assessed by the WOMAC scale resulting in a loss of function for both Triamcinolone and placebo (p value=0.17). Stiffness was also assessed by the WOMAC scale resulting in no difference (-0.59 vs -0.53) (p value= 0.79). Another secondary outcome was pain which was assessed by the VAS Pain score. The result was no difference in pain between groups (-2.7 vs -7.6) (p value=0.26).

Subgroup Analysis

There were no subgroup analysis listed in this study.

Adverse Events

Treatment-Related Adverse Events

  • Triamcinolone Group (5 events)
    • Facial Flushing (1 event)
    • Infection Site Pain (4 events)
  • Saline Group (3 events)
    • Cellulitis (1 event)
    • Injection Site Pain (2 events)

Criticisms

  • Pain was not measured within the first 4-week period after each injection. Therefore, any benefit of pain improvement within the 3-month period between each injection could have been missed.(3)
  • Patients were not asked to discontinue any medications they were already taking, so that may have contributed to any differences in symptom outcomes for the subjects.(3)
  • High expectations and large placebo responses could have affected assessments of effects.(4)
  • The ultrasonography used to measure inflammation at the osteoarthritic knee lacks specificity in identifying inflammation.(5)
  • Dose or frequency of regimen was insufficient to generate anti-inflammatory effect to reduce pain long term.(5)

Funding

This study was supported by grants from the National Institute for Arthritis and Musculoskeletal Disorders and Skin Diseases and National Center for Advancing Translational Sciences, National Institutes of Health.

Further Reading

1. Biscaldi, Lauren. “Knee Osteoarthritis: Intra-Articular Triamcinolone vs Saline Injection.” Rheumatology Advisor, 26 May 2017, www.rheumatologyadvisor.com/osteoarthritis/saline-vs-active-injection-for-knee-oa-cartilage-volume-and-pain/article/664707/.

2. Hochberg, Marc C., et al. “American College of Rheumatology 2012 Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee.” Arthritis Care & Research, vol. 64, no. 4, 2012, pp. 465–474., doi:10.1002/acr.21596.

3. Arroll B, Goodyear-Smith F. Corticosteroid injections for osteoarthritis of the knee: meta-analysis. BMJ. 2004;328(7444):869.PubMed

4. Bannuru RR, McAlindon TE, Sullivan MC, Wong JB, Kent DM, Schmid CH. Effectiveness and implications of alternative placebo treatments: a systematic review and network meta-analysis of osteoarthritis trials. Ann Intern Med. 2015;163(5):365-372.PubMed

5. Chao J, Wu C, Sun B, et al. Inflammatory characteristics on ultrasound predict poorer longterm response to intraarticular corticosteroid injections in knee osteoarthritis. J Rheumatol. 2010;37(3):650-655.