correspondence
Oliver Bautista, Ph.D. Alain Luxembourg, M.D., Ph.D. Merck Kenilworth, NJ Since publication of their article, the authors report no further potential conflict of interest. 1. Use of 9-valent human papillomavirus (HPV) vaccine: up-
dated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep 2015;64:300-4.
2. Schiller JT, Castellsagué X, Garland SM. A review of clinical
trials of human papillomavirus prophylactic vaccines. Vaccine 2012;30:Suppl 5:F123-F138. 3. Tabrizi SN, Brotherton JM, Kaldor JM, et al. Fall in human papillomavirus prevalence following a national vaccination program. J Infect Dis 2012;206:1645-51. 4. Drolet M, Bénard É, Boily MC, et al. Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 2015;15:565-80. DOI: 10.1056/NEJMc1504359
Viscosupplementation for Osteoarthritis of the Knee To the Editor: I am a knee surgeon and specialist in knee replacement, and I have three remarks regarding the review article by Hunter (March 12 issue).1 First, I want to emphasize that viscosupplementation can have the same effect on symptoms as antiinflammatory agents but without their side effects in patients with conditions (such as renal insufficiency) that coexist with arthritis. This is especially important in patients who require knee replacement, many of whom present with renal insufficiency, are receiving anticoagulation therapy, or have cardiac problems.2 Second, tramadol for arthritis can lead to more chronic pain after total knee replacement, since long-term use of opioids or opioid-related drugs is one of the main risk factors for persistent postsurgical pain.3 Finally, the availability of viscosupplementation allows surgeons to treat patients with arthritic pain before the stage of bone-on-bone arthritis. Studies have shown that early surgery, before this stage is reached, may be associated with persistent postsurgical pain after total knee replacement.4 Viscosupplementation might help the patient during the most painful period without the need for surgery, which sometimes can be postponed for many years.5 Emmanuel Thienpont, M.D., M.B.A. University Hospital Saint Luc Brussels, Belgium Dr. Thienpont reports receiving royalties from Biomet, ConvaTec, Medacta, and Zimmer and consulting fees from Arthrex, Biomet, DePuy, Medacta, and Zimmer, and holding warrants and stock in TiGenix. No other potential conflict of interest relevant to this letter was reported. 1. Hunter DJ. Viscosupplementation for osteoarthritis of the
knee. N Engl J Med 2015;372:1040-7.
2. Coxib and Traditional NSAID Trialists’ (CNT) Collaboration.
Vascular and upper gastrointestinal effects of non-steroidal antiinflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013;382:769-79. 3. Zywiel MG, Stroh DA, Lee SY, Bonutti PM, Mont MA. Chron-
ic opioid use prior to total knee arthroplasty. J Bone Joint Surg Am 2011;93:1988-93. 4. Merle-Vincent F, Couris CM, Schott AM, et al. Factors predicting patient satisfaction 2 years after total knee arthroplasty for osteoarthritis. Joint Bone Spine 2011;78:383-6. 5. Dye SF. The pathophysiology of patellofemoral pain: a tissue homeostasis perspective. Clin Orthop Relat Res 2005;436:100-10. DOI: 10.1056/NEJMc1505801
To the Editor: Hunter cites the American Academy of Orthopaedic Surgeons 2009 clinical practice guideline, and he states, “it was determined that the evidence was inconclusive and a recommendation could not be made for or against the use of intraarticular hyaluronate.” The second edition of this guideline, released in 2013, stated, “We cannot recommend using hyaluronic acid for patients with symptomatic osteoarthritis of the knee.” Hunter also says, “True joint infections have also been reported, but these appear to be rare,” and he cites two case reports from 2006. I am a recently retired family doctor and the current medical director of the Cooley Dickinson Physician Hospital Organization, and I know of three cases. It is time to stop prescribing viscosupplementation for osteoarthritis of the knee. Samuel Gladstone, M.D. Cooley Dickinson Physician Hospital Organization Northampton, MA [email protected] No potential conflict of interest relevant to this letter was reported. DOI: 10.1056/NEJMc1505801
To the Editor: Hunter advises against the use of intraarticular hyaluronate in a 67-year-old woman with moderate right-knee osteoarthritis. However, in patients in China with osteoarthritis of the knee, intraarticular hyaluronate is used extensively. More than 1.5 million patients with osteoarthritis have been treated with Sofast, a brand
n engl j med 372;26 nejm.org june 25, 2015
2569
The New England Journal of Medicine Downloaded from nejm.org at NYU WASHINGTON SQUARE CAMPUS on June 30, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
correspondence
of sodium hyaluronate injection (Shandong, Freda Biochem) that holds more than 70% of the market share in China. Revenues from the sale of Sofast were 58.34 million yuan (approximately $8.76 million) in 2010, 67.09 million yuan (approximately $10.18 million) in 2011, and 75.81 million yuan (approximately $12.01 million) in 2012.1 If intraarticular hyaluronate is indeed useless, this money has been wasted. However, a beneficial effect of intraarticular hyaluronate, at least short-term efficacy, has been observed by many doctors in clinical practice in China. We wonder whether the guidelines2-4 have considered the short-term efficacy. We are expecting further evidence of efficacy, and a high-quality, multiple-center, large-sample, randomized, controlled trial is about to begin in China. Chao Zeng, M.D. Shu-guang Gao, M.D., Ph.D. Guang-hua Lei, M.D., Ph.D.
least of which is the potential for toxicity and abuse.2 Clinicians also need to be judicious about selection of candidates for total knee replacement, since up to 25% of persons are not suitable candidates for this surgery and have poor outcomes.3 I agree with Gladstone that the widespread use of viscosupplementation is not supported by current evidence, and given the potential for harm and the costs involved, its use should be discontinued. Recent guidelines are clearer in their stance in discouraging the use of hyaluronate, but it may take decades for practice to reflect this evidence, as it does with many other interventions for which there is solid evidence and translational failure. Zeng and colleagues point out their experience, and in so doing promote the most widely used viscosupplement in China. Although there may be a Chinese-specific response to this intervention, data from trials to support the favorable stance toward viscosupplementation, rather than Xiangya Hospital Changsha, China anecdotes and sales results, would be helpful. [email protected] Just because something is widely practiced and No potential conflict of interest relevant to this letter was recosts the health system a lot of money does not ported. mean that the practice should continue. Knee 1. Prospectus for Shandong Commercial Group Company Limited’s 1st short-term commercial paper issuance in 2014 (in arthroscopy in patients with knee osteoarthritis Chinese) (http://pg.jrj.com.cn/acc/CN_DISC/BOND_NT/2014/03/04/ is a clear and proximate example4; there is wideIs00000000000008ztgv.pdf). spread evidence of a lack of efficacy, real poten2. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. tial for harm, and an associated cost, yet at this Osteoarthritis Cartilage 2014;22:363-88. time, practice patterns suggest no diminution in 3. Richmond J, Hunter D, Irrgang J, et al. Treatment of osteothe frequency with which it is used. arthritis of the knee (nonarthroplasty). J Am Acad Orthop Surg Recent guidelines provide many safe and effec2009;17:591-600. 4. Hochberg MC, Altman RD, April KT, et al. American College of tive treatment alternatives for the care of persons Rheumatology 2012 recommendations for the use of nonpharmawith knee osteoarthritis. I would encourage the cologic and pharmacologic therapies in osteoarthritis of the hand, appropriate use of these therapies. It is time to hip, and knee. Arthritis Care Res (Hoboken) 2012;64:465-74. DOI: 10.1056/NEJMc1505801 put into practice what has been shown to work and discourage the use of products that do not. The Author Replies: In reply to Thienpont: David J. Hunter, M.B., B.S., Ph.D. rather than limit one’s options to viscosupple- University of Sydney mentation and joint replacement, I would en- Sydney, NSW, Australia Since publication of his article, the author reports no further courage the use of various treatment options (inpotential conflict of interest. cluding diet and exercise) that have been shown 1. Birnbaum HG, White AG, Schiller M, Waldman T, Cleveland to be safe and effective at all stages of osteoar- JM, Roland CL. Societal costs of prescription opioid abuse, depenthritis and are featured in most guidelines.1 It is dence, and misuse in the United States. Pain Med 2011;12:657-67. Nelson AE, Allen KD, Golightly YM, Goode AP, Jordan JM. important to be aware of the potential adverse 2. A systematic review of recommendations and guidelines for the effects with the use of nonsteroidal antiinflam- management of osteoarthritis: the Chronic Osteoarthritis Manmatory drugs, especially in persons who are at agement Initiative of the U.S. Bone and Joint Initiative. Semin Rheum 2014;43:701-12. risk for cardiovascular or gastrointestinal toxicity. Arthritis 3. Dowsey MM, Gunn J, Choong PF. Selecting those to refer for Tramadol is inconsistently recommended in treat- joint replacement: who will likely benefit and who will not? Best ment guidelines for osteoarthritis, and its inclu- Pract Res Clin Rheumatol 2014;28:157-71. Lohmander LS, Roos EM. The evidence base for orthopaesion in the review indicated that it is an option 4. dics and sports medicine. BMJ 2015;350:g7835. — its use was not advocated. There are a number DOI: 10.1056/NEJMc1505801 of real concerns with the use of opioids, not the Correspondence Copyright © 2015 Massachusetts Medical Society. 2570
n engl j med 372;26 nejm.org june 25, 2015
The New England Journal of Medicine Downloaded from nejm.org at NYU WASHINGTON SQUARE CAMPUS on June 30, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
Oliver Bautista, Ph.D. Alain Luxembourg, M.D., Ph.D. Merck Kenilworth, NJ Since publication of their article, the authors report no further potential conflict of interest. 1. Use of 9-valent human papillomavirus (HPV) vaccine: up-
dated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep 2015;64:300-4.
2. Schiller JT, Castellsagué X, Garland SM. A review of clinical
trials of human papillomavirus prophylactic vaccines. Vaccine 2012;30:Suppl 5:F123-F138. 3. Tabrizi SN, Brotherton JM, Kaldor JM, et al. Fall in human papillomavirus prevalence following a national vaccination program. J Infect Dis 2012;206:1645-51. 4. Drolet M, Bénard É, Boily MC, et al. Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 2015;15:565-80. DOI: 10.1056/NEJMc1504359
Viscosupplementation for Osteoarthritis of the Knee To the Editor: I am a knee surgeon and specialist in knee replacement, and I have three remarks regarding the review article by Hunter (March 12 issue).1 First, I want to emphasize that viscosupplementation can have the same effect on symptoms as antiinflammatory agents but without their side effects in patients with conditions (such as renal insufficiency) that coexist with arthritis. This is especially important in patients who require knee replacement, many of whom present with renal insufficiency, are receiving anticoagulation therapy, or have cardiac problems.2 Second, tramadol for arthritis can lead to more chronic pain after total knee replacement, since long-term use of opioids or opioid-related drugs is one of the main risk factors for persistent postsurgical pain.3 Finally, the availability of viscosupplementation allows surgeons to treat patients with arthritic pain before the stage of bone-on-bone arthritis. Studies have shown that early surgery, before this stage is reached, may be associated with persistent postsurgical pain after total knee replacement.4 Viscosupplementation might help the patient during the most painful period without the need for surgery, which sometimes can be postponed for many years.5 Emmanuel Thienpont, M.D., M.B.A. University Hospital Saint Luc Brussels, Belgium Dr. Thienpont reports receiving royalties from Biomet, ConvaTec, Medacta, and Zimmer and consulting fees from Arthrex, Biomet, DePuy, Medacta, and Zimmer, and holding warrants and stock in TiGenix. No other potential conflict of interest relevant to this letter was reported. 1. Hunter DJ. Viscosupplementation for osteoarthritis of the
knee. N Engl J Med 2015;372:1040-7.
2. Coxib and Traditional NSAID Trialists’ (CNT) Collaboration.
Vascular and upper gastrointestinal effects of non-steroidal antiinflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013;382:769-79. 3. Zywiel MG, Stroh DA, Lee SY, Bonutti PM, Mont MA. Chron-
ic opioid use prior to total knee arthroplasty. J Bone Joint Surg Am 2011;93:1988-93. 4. Merle-Vincent F, Couris CM, Schott AM, et al. Factors predicting patient satisfaction 2 years after total knee arthroplasty for osteoarthritis. Joint Bone Spine 2011;78:383-6. 5. Dye SF. The pathophysiology of patellofemoral pain: a tissue homeostasis perspective. Clin Orthop Relat Res 2005;436:100-10. DOI: 10.1056/NEJMc1505801
To the Editor: Hunter cites the American Academy of Orthopaedic Surgeons 2009 clinical practice guideline, and he states, “it was determined that the evidence was inconclusive and a recommendation could not be made for or against the use of intraarticular hyaluronate.” The second edition of this guideline, released in 2013, stated, “We cannot recommend using hyaluronic acid for patients with symptomatic osteoarthritis of the knee.” Hunter also says, “True joint infections have also been reported, but these appear to be rare,” and he cites two case reports from 2006. I am a recently retired family doctor and the current medical director of the Cooley Dickinson Physician Hospital Organization, and I know of three cases. It is time to stop prescribing viscosupplementation for osteoarthritis of the knee. Samuel Gladstone, M.D. Cooley Dickinson Physician Hospital Organization Northampton, MA [email protected] No potential conflict of interest relevant to this letter was reported. DOI: 10.1056/NEJMc1505801
To the Editor: Hunter advises against the use of intraarticular hyaluronate in a 67-year-old woman with moderate right-knee osteoarthritis. However, in patients in China with osteoarthritis of the knee, intraarticular hyaluronate is used extensively. More than 1.5 million patients with osteoarthritis have been treated with Sofast, a brand
n engl j med 372;26 nejm.org june 25, 2015
2569
The New England Journal of Medicine Downloaded from nejm.org at NYU WASHINGTON SQUARE CAMPUS on June 30, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
correspondence
of sodium hyaluronate injection (Shandong, Freda Biochem) that holds more than 70% of the market share in China. Revenues from the sale of Sofast were 58.34 million yuan (approximately $8.76 million) in 2010, 67.09 million yuan (approximately $10.18 million) in 2011, and 75.81 million yuan (approximately $12.01 million) in 2012.1 If intraarticular hyaluronate is indeed useless, this money has been wasted. However, a beneficial effect of intraarticular hyaluronate, at least short-term efficacy, has been observed by many doctors in clinical practice in China. We wonder whether the guidelines2-4 have considered the short-term efficacy. We are expecting further evidence of efficacy, and a high-quality, multiple-center, large-sample, randomized, controlled trial is about to begin in China. Chao Zeng, M.D. Shu-guang Gao, M.D., Ph.D. Guang-hua Lei, M.D., Ph.D.
least of which is the potential for toxicity and abuse.2 Clinicians also need to be judicious about selection of candidates for total knee replacement, since up to 25% of persons are not suitable candidates for this surgery and have poor outcomes.3 I agree with Gladstone that the widespread use of viscosupplementation is not supported by current evidence, and given the potential for harm and the costs involved, its use should be discontinued. Recent guidelines are clearer in their stance in discouraging the use of hyaluronate, but it may take decades for practice to reflect this evidence, as it does with many other interventions for which there is solid evidence and translational failure. Zeng and colleagues point out their experience, and in so doing promote the most widely used viscosupplement in China. Although there may be a Chinese-specific response to this intervention, data from trials to support the favorable stance toward viscosupplementation, rather than Xiangya Hospital Changsha, China anecdotes and sales results, would be helpful. [email protected] Just because something is widely practiced and No potential conflict of interest relevant to this letter was recosts the health system a lot of money does not ported. mean that the practice should continue. Knee 1. Prospectus for Shandong Commercial Group Company Limited’s 1st short-term commercial paper issuance in 2014 (in arthroscopy in patients with knee osteoarthritis Chinese) (http://pg.jrj.com.cn/acc/CN_DISC/BOND_NT/2014/03/04/ is a clear and proximate example4; there is wideIs00000000000008ztgv.pdf). spread evidence of a lack of efficacy, real poten2. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. tial for harm, and an associated cost, yet at this Osteoarthritis Cartilage 2014;22:363-88. time, practice patterns suggest no diminution in 3. Richmond J, Hunter D, Irrgang J, et al. Treatment of osteothe frequency with which it is used. arthritis of the knee (nonarthroplasty). J Am Acad Orthop Surg Recent guidelines provide many safe and effec2009;17:591-600. 4. Hochberg MC, Altman RD, April KT, et al. American College of tive treatment alternatives for the care of persons Rheumatology 2012 recommendations for the use of nonpharmawith knee osteoarthritis. I would encourage the cologic and pharmacologic therapies in osteoarthritis of the hand, appropriate use of these therapies. It is time to hip, and knee. Arthritis Care Res (Hoboken) 2012;64:465-74. DOI: 10.1056/NEJMc1505801 put into practice what has been shown to work and discourage the use of products that do not. The Author Replies: In reply to Thienpont: David J. Hunter, M.B., B.S., Ph.D. rather than limit one’s options to viscosupple- University of Sydney mentation and joint replacement, I would en- Sydney, NSW, Australia Since publication of his article, the author reports no further courage the use of various treatment options (inpotential conflict of interest. cluding diet and exercise) that have been shown 1. Birnbaum HG, White AG, Schiller M, Waldman T, Cleveland to be safe and effective at all stages of osteoar- JM, Roland CL. Societal costs of prescription opioid abuse, depenthritis and are featured in most guidelines.1 It is dence, and misuse in the United States. Pain Med 2011;12:657-67. Nelson AE, Allen KD, Golightly YM, Goode AP, Jordan JM. important to be aware of the potential adverse 2. A systematic review of recommendations and guidelines for the effects with the use of nonsteroidal antiinflam- management of osteoarthritis: the Chronic Osteoarthritis Manmatory drugs, especially in persons who are at agement Initiative of the U.S. Bone and Joint Initiative. Semin Rheum 2014;43:701-12. risk for cardiovascular or gastrointestinal toxicity. Arthritis 3. Dowsey MM, Gunn J, Choong PF. Selecting those to refer for Tramadol is inconsistently recommended in treat- joint replacement: who will likely benefit and who will not? Best ment guidelines for osteoarthritis, and its inclu- Pract Res Clin Rheumatol 2014;28:157-71. Lohmander LS, Roos EM. The evidence base for orthopaesion in the review indicated that it is an option 4. dics and sports medicine. BMJ 2015;350:g7835. — its use was not advocated. There are a number DOI: 10.1056/NEJMc1505801 of real concerns with the use of opioids, not the Correspondence Copyright © 2015 Massachusetts Medical Society. 2570
n engl j med 372;26 nejm.org june 25, 2015
The New England Journal of Medicine Downloaded from nejm.org at NYU WASHINGTON SQUARE CAMPUS on June 30, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
