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How do hyaluronic acid and corticosteroid injections compare for knee OA relief?
EVIDENCE SUMMARY
A 2015 network meta-analysis of 137 RCTs with 33,243 patients (ages 45-76 years) with knee OA compared the effectiveness of a variety of treatments including intra-articular CS and HA.1 At 3 months, the effect on pain was not significantly different between the CS and HA groups (12 trials; effect size [ES]=0.02; 95% confidence interval [CI], -0.12 to 0.17). However, a small but significant improvement in function was noted (scoring system not defined) at 3 months favoring HA (ES=0.24; 95% CI, 0.06-0.43; number of trials not specified).
At 3 and 6 months, HA improves pain, but not function, more than CS
Another meta-analysis published in 2015 examined the effectiveness of intra-articular CS and HA in 7 RCTs with 583 patients with knee OA.2 All 7 trials were included in the network meta-analysis and discussed separately to evaluate different time points.
Pain at one month wasn’t significantly different using a visual analog score (VAS) of one to 100 (4 trials; 245 patients; mean difference [MD]=1.66 points; 95% CI, -0.90 to 4.23). At 3 and 6 months, the HA group reported significantly reduced pain compared with the CS group (3 months: 3 trials; 320 patients; MD=12.58 points; 95% CI, -17.76 to -7.40; 6 months: 5 trials; 411 patients; MD=9.01 points; 95% CI, -12.62 to -5.40). There were no significant differences in function outcomes (Index of severity for OA of the knee by Lequesne et al; The Knee Society Clinical Rating System), maximum flexion, or adverse events.
Triamcinolone improves pain, function, but not for long
A 2016 double-blind RCT of 110 patients with knee OA compared intra-articular HA and triamcinolone, assessing pain and function at intervals between 24 hours and 6 months.3 Patients in the HA group received a single injection of 6 mL hylan G-F 20 (Synvisc); patients in the CS group received 1 mL of triamcinolone acetonide 40 mg and 5 mL of 1% lidocaine with epinephrine.
The CS group reported significantly less pain (VAS score 1 to 100) at 24 hours than the HA group (24 points vs 36 points; P=.002); relief lasted as long as one week (14 points vs 23 points; P=.018). After the first week, no difference was seen in pain between groups for as long as 6 months.
Function, assessed by a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC 1 to 100; higher score indicates worse pain, stiffness, and function) showed a significant improvement with CS at 2 weeks (25 points vs 31 points; P=.03), but no difference at any other time point up to 6 months.
HA (mostly) improves pain, function more than betamethasone
A 2015 RCT of 200 patients with knee OA compared the effectiveness of intra-articular HA and betamethasone.4 Evaluators were blinded and assessments were made at 3, 6, 9, and 12 months. The HA group received 2.5 mL of 1% HA (Suprahyal); the CS group received betamethasone dipropionate 5 mg plus betamethasone sodium phosphate 2 mg in 1 mL.
The CS group had significantly less pain (VAS 1 to 10) at 3 months compared with the HA group (2.2 points vs 3.1 points; P=.004), but the HA group had less pain at all other time points (6 months: 3.9 points vs 2.4 points; P=.0001; 9 months: 5.5 points vs 3.6 points; P=.0001; 12 months: 6 points vs 4.1 points; P=.0001).
The WOMAC function subscores (0 to 68; lower indicates more function) were significantly better at all follow-up points in the HA group compared with the CS group (3 months: 19 vs 25; P=.0001; 6 months: 17 vs 29; P=.0001; 9 months: 25 vs 42; P=.0001; 12 months: 28 vs 42; P=.0001).4
RECOMMENDATIONS
The American Academy of Orthopaedic Surgeons 2013 work group couldn’t recommend for or against using intra-articular CS for patients with symptomatic knee OA based on inconclusive evidence.5 They also couldn’t recommend using HA (SOR: strong).
The National Institute for Health and Care Excellence (NICE) stated in 2008 that intra-articular CS injections should be considered as an adjunct to core treatments for the relief of moderate to severe pain in people with OA.6 In 2014, NICE recommended against offering intra-articular HA injections for managing OA.
The US Veterans Administration and Department of Defense have issued guidelines stating that clinicians may consider intra-articular CS injections for patients with symptomatic knee OA (US Preventive Services Task Force [USPSTF] Grade B).7 They report insufficient evidence to recommend for or against the use of intra-articular HA with the caveat that HA may be considered for patients who don’t respond adequately to nonpharmacologic measures and who have an inadequate response, intolerable adverse events, or contraindications to other pharmacologic therapies (USPSTF Grade I).
1. Bannuru RR, Schmid CH, Kent DM, et al. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162:46-54.
2. Wang F, He X. Intra-articular hyaluronic acid and corticosteroids in the treatment of knee osteoarthritis: a meta-analysis. Exp Ther Med. 2015;9:493-500.
3. Tammachote N, Kanitnate S, Yakumpor T, et al. Intra-articular, single-shot Hylan G-F 20 hyaluronic acid injection compared with corticosteroid in knee osteoarthritis: a double-blind, randomized controlled trial. J Bone Joint Surg Am. 2016;98:885-892.
4. Trueba Davalillo CA, Trueba Vasavilbaso C, Navarrete Alvarez JM, et al. Clinical efficacy of intra-articular injections in knee osteoarthritis: a prospective randomized study comparing hyaluronic acid and betamethasone. Open Access Rheumatol Res Rev. 2015;7:9-18.
5. American Academy of Orthopaedic Surgeons. Treatment of Osteoarthritis of the Knee: Evidence-Based Guideline. 2nd ed. Available at: http://www.aaos.org/cc_files/aaosorg/research/guidelines/treatmentofosteoarthritisofthekneeguideline.pdf. Accessed May 15, 2016.
6. National Institute for Health and Care Excellence. Osteoarthritis: Care and Management. Available at: https://www.nice.org.uk/guidance/cg177/chapter/1-recommendations. Accessed May 15, 2016.
7. United States Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for the Non-Surgical Management of Hip and Knee Osteoarthritis. Available at: http://www.healthquality.va.gov/guidelines/CD/OA/VADoDOACPGFINAL090214.pdf. Accessed May 15, 2016.
EVIDENCE SUMMARY
A 2015 network meta-analysis of 137 RCTs with 33,243 patients (ages 45-76 years) with knee OA compared the effectiveness of a variety of treatments including intra-articular CS and HA.1 At 3 months, the effect on pain was not significantly different between the CS and HA groups (12 trials; effect size [ES]=0.02; 95% confidence interval [CI], -0.12 to 0.17). However, a small but significant improvement in function was noted (scoring system not defined) at 3 months favoring HA (ES=0.24; 95% CI, 0.06-0.43; number of trials not specified).
At 3 and 6 months, HA improves pain, but not function, more than CS
Another meta-analysis published in 2015 examined the effectiveness of intra-articular CS and HA in 7 RCTs with 583 patients with knee OA.2 All 7 trials were included in the network meta-analysis and discussed separately to evaluate different time points.
Pain at one month wasn’t significantly different using a visual analog score (VAS) of one to 100 (4 trials; 245 patients; mean difference [MD]=1.66 points; 95% CI, -0.90 to 4.23). At 3 and 6 months, the HA group reported significantly reduced pain compared with the CS group (3 months: 3 trials; 320 patients; MD=12.58 points; 95% CI, -17.76 to -7.40; 6 months: 5 trials; 411 patients; MD=9.01 points; 95% CI, -12.62 to -5.40). There were no significant differences in function outcomes (Index of severity for OA of the knee by Lequesne et al; The Knee Society Clinical Rating System), maximum flexion, or adverse events.
Triamcinolone improves pain, function, but not for long
A 2016 double-blind RCT of 110 patients with knee OA compared intra-articular HA and triamcinolone, assessing pain and function at intervals between 24 hours and 6 months.3 Patients in the HA group received a single injection of 6 mL hylan G-F 20 (Synvisc); patients in the CS group received 1 mL of triamcinolone acetonide 40 mg and 5 mL of 1% lidocaine with epinephrine.
The CS group reported significantly less pain (VAS score 1 to 100) at 24 hours than the HA group (24 points vs 36 points; P=.002); relief lasted as long as one week (14 points vs 23 points; P=.018). After the first week, no difference was seen in pain between groups for as long as 6 months.
Function, assessed by a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC 1 to 100; higher score indicates worse pain, stiffness, and function) showed a significant improvement with CS at 2 weeks (25 points vs 31 points; P=.03), but no difference at any other time point up to 6 months.
HA (mostly) improves pain, function more than betamethasone
A 2015 RCT of 200 patients with knee OA compared the effectiveness of intra-articular HA and betamethasone.4 Evaluators were blinded and assessments were made at 3, 6, 9, and 12 months. The HA group received 2.5 mL of 1% HA (Suprahyal); the CS group received betamethasone dipropionate 5 mg plus betamethasone sodium phosphate 2 mg in 1 mL.
The CS group had significantly less pain (VAS 1 to 10) at 3 months compared with the HA group (2.2 points vs 3.1 points; P=.004), but the HA group had less pain at all other time points (6 months: 3.9 points vs 2.4 points; P=.0001; 9 months: 5.5 points vs 3.6 points; P=.0001; 12 months: 6 points vs 4.1 points; P=.0001).
The WOMAC function subscores (0 to 68; lower indicates more function) were significantly better at all follow-up points in the HA group compared with the CS group (3 months: 19 vs 25; P=.0001; 6 months: 17 vs 29; P=.0001; 9 months: 25 vs 42; P=.0001; 12 months: 28 vs 42; P=.0001).4
RECOMMENDATIONS
The American Academy of Orthopaedic Surgeons 2013 work group couldn’t recommend for or against using intra-articular CS for patients with symptomatic knee OA based on inconclusive evidence.5 They also couldn’t recommend using HA (SOR: strong).
The National Institute for Health and Care Excellence (NICE) stated in 2008 that intra-articular CS injections should be considered as an adjunct to core treatments for the relief of moderate to severe pain in people with OA.6 In 2014, NICE recommended against offering intra-articular HA injections for managing OA.
The US Veterans Administration and Department of Defense have issued guidelines stating that clinicians may consider intra-articular CS injections for patients with symptomatic knee OA (US Preventive Services Task Force [USPSTF] Grade B).7 They report insufficient evidence to recommend for or against the use of intra-articular HA with the caveat that HA may be considered for patients who don’t respond adequately to nonpharmacologic measures and who have an inadequate response, intolerable adverse events, or contraindications to other pharmacologic therapies (USPSTF Grade I).
EVIDENCE SUMMARY
A 2015 network meta-analysis of 137 RCTs with 33,243 patients (ages 45-76 years) with knee OA compared the effectiveness of a variety of treatments including intra-articular CS and HA.1 At 3 months, the effect on pain was not significantly different between the CS and HA groups (12 trials; effect size [ES]=0.02; 95% confidence interval [CI], -0.12 to 0.17). However, a small but significant improvement in function was noted (scoring system not defined) at 3 months favoring HA (ES=0.24; 95% CI, 0.06-0.43; number of trials not specified).
At 3 and 6 months, HA improves pain, but not function, more than CS
Another meta-analysis published in 2015 examined the effectiveness of intra-articular CS and HA in 7 RCTs with 583 patients with knee OA.2 All 7 trials were included in the network meta-analysis and discussed separately to evaluate different time points.
Pain at one month wasn’t significantly different using a visual analog score (VAS) of one to 100 (4 trials; 245 patients; mean difference [MD]=1.66 points; 95% CI, -0.90 to 4.23). At 3 and 6 months, the HA group reported significantly reduced pain compared with the CS group (3 months: 3 trials; 320 patients; MD=12.58 points; 95% CI, -17.76 to -7.40; 6 months: 5 trials; 411 patients; MD=9.01 points; 95% CI, -12.62 to -5.40). There were no significant differences in function outcomes (Index of severity for OA of the knee by Lequesne et al; The Knee Society Clinical Rating System), maximum flexion, or adverse events.
Triamcinolone improves pain, function, but not for long
A 2016 double-blind RCT of 110 patients with knee OA compared intra-articular HA and triamcinolone, assessing pain and function at intervals between 24 hours and 6 months.3 Patients in the HA group received a single injection of 6 mL hylan G-F 20 (Synvisc); patients in the CS group received 1 mL of triamcinolone acetonide 40 mg and 5 mL of 1% lidocaine with epinephrine.
The CS group reported significantly less pain (VAS score 1 to 100) at 24 hours than the HA group (24 points vs 36 points; P=.002); relief lasted as long as one week (14 points vs 23 points; P=.018). After the first week, no difference was seen in pain between groups for as long as 6 months.
Function, assessed by a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC 1 to 100; higher score indicates worse pain, stiffness, and function) showed a significant improvement with CS at 2 weeks (25 points vs 31 points; P=.03), but no difference at any other time point up to 6 months.
HA (mostly) improves pain, function more than betamethasone
A 2015 RCT of 200 patients with knee OA compared the effectiveness of intra-articular HA and betamethasone.4 Evaluators were blinded and assessments were made at 3, 6, 9, and 12 months. The HA group received 2.5 mL of 1% HA (Suprahyal); the CS group received betamethasone dipropionate 5 mg plus betamethasone sodium phosphate 2 mg in 1 mL.
The CS group had significantly less pain (VAS 1 to 10) at 3 months compared with the HA group (2.2 points vs 3.1 points; P=.004), but the HA group had less pain at all other time points (6 months: 3.9 points vs 2.4 points; P=.0001; 9 months: 5.5 points vs 3.6 points; P=.0001; 12 months: 6 points vs 4.1 points; P=.0001).
The WOMAC function subscores (0 to 68; lower indicates more function) were significantly better at all follow-up points in the HA group compared with the CS group (3 months: 19 vs 25; P=.0001; 6 months: 17 vs 29; P=.0001; 9 months: 25 vs 42; P=.0001; 12 months: 28 vs 42; P=.0001).4
RECOMMENDATIONS
The American Academy of Orthopaedic Surgeons 2013 work group couldn’t recommend for or against using intra-articular CS for patients with symptomatic knee OA based on inconclusive evidence.5 They also couldn’t recommend using HA (SOR: strong).
The National Institute for Health and Care Excellence (NICE) stated in 2008 that intra-articular CS injections should be considered as an adjunct to core treatments for the relief of moderate to severe pain in people with OA.6 In 2014, NICE recommended against offering intra-articular HA injections for managing OA.
The US Veterans Administration and Department of Defense have issued guidelines stating that clinicians may consider intra-articular CS injections for patients with symptomatic knee OA (US Preventive Services Task Force [USPSTF] Grade B).7 They report insufficient evidence to recommend for or against the use of intra-articular HA with the caveat that HA may be considered for patients who don’t respond adequately to nonpharmacologic measures and who have an inadequate response, intolerable adverse events, or contraindications to other pharmacologic therapies (USPSTF Grade I).
1. Bannuru RR, Schmid CH, Kent DM, et al. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162:46-54.
2. Wang F, He X. Intra-articular hyaluronic acid and corticosteroids in the treatment of knee osteoarthritis: a meta-analysis. Exp Ther Med. 2015;9:493-500.
3. Tammachote N, Kanitnate S, Yakumpor T, et al. Intra-articular, single-shot Hylan G-F 20 hyaluronic acid injection compared with corticosteroid in knee osteoarthritis: a double-blind, randomized controlled trial. J Bone Joint Surg Am. 2016;98:885-892.
4. Trueba Davalillo CA, Trueba Vasavilbaso C, Navarrete Alvarez JM, et al. Clinical efficacy of intra-articular injections in knee osteoarthritis: a prospective randomized study comparing hyaluronic acid and betamethasone. Open Access Rheumatol Res Rev. 2015;7:9-18.
5. American Academy of Orthopaedic Surgeons. Treatment of Osteoarthritis of the Knee: Evidence-Based Guideline. 2nd ed. Available at: http://www.aaos.org/cc_files/aaosorg/research/guidelines/treatmentofosteoarthritisofthekneeguideline.pdf. Accessed May 15, 2016.
6. National Institute for Health and Care Excellence. Osteoarthritis: Care and Management. Available at: https://www.nice.org.uk/guidance/cg177/chapter/1-recommendations. Accessed May 15, 2016.
7. United States Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for the Non-Surgical Management of Hip and Knee Osteoarthritis. Available at: http://www.healthquality.va.gov/guidelines/CD/OA/VADoDOACPGFINAL090214.pdf. Accessed May 15, 2016.
1. Bannuru RR, Schmid CH, Kent DM, et al. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162:46-54.
2. Wang F, He X. Intra-articular hyaluronic acid and corticosteroids in the treatment of knee osteoarthritis: a meta-analysis. Exp Ther Med. 2015;9:493-500.
3. Tammachote N, Kanitnate S, Yakumpor T, et al. Intra-articular, single-shot Hylan G-F 20 hyaluronic acid injection compared with corticosteroid in knee osteoarthritis: a double-blind, randomized controlled trial. J Bone Joint Surg Am. 2016;98:885-892.
4. Trueba Davalillo CA, Trueba Vasavilbaso C, Navarrete Alvarez JM, et al. Clinical efficacy of intra-articular injections in knee osteoarthritis: a prospective randomized study comparing hyaluronic acid and betamethasone. Open Access Rheumatol Res Rev. 2015;7:9-18.
5. American Academy of Orthopaedic Surgeons. Treatment of Osteoarthritis of the Knee: Evidence-Based Guideline. 2nd ed. Available at: http://www.aaos.org/cc_files/aaosorg/research/guidelines/treatmentofosteoarthritisofthekneeguideline.pdf. Accessed May 15, 2016.
6. National Institute for Health and Care Excellence. Osteoarthritis: Care and Management. Available at: https://www.nice.org.uk/guidance/cg177/chapter/1-recommendations. Accessed May 15, 2016.
7. United States Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for the Non-Surgical Management of Hip and Knee Osteoarthritis. Available at: http://www.healthquality.va.gov/guidelines/CD/OA/VADoDOACPGFINAL090214.pdf. Accessed May 15, 2016.
Evidence-based answers from the Family Physicians Inquiries Network
EVIDENCE-BASED ANSWER:
Inconsistent evidence shows a small amount of pain relief early (one week to 3 months) with corticosteroid (CS) injections and an equally small improvement in pain relief and function later (3 to 12 months) with hyaluronic acid (HA) injections (strength of recommendation [SOR]: B, meta-analysis of a randomized controlled trial [RCT] and inconsistent RCTs).
Guidelines state that CS injections can be considered for symptomatic knee osteoarthritis (OA), but that insufficient evidence exists to recommend HA injections (SOR: B, evidence-based guidelines).
