Advertisement

Osteoarthritis pp 211-234 | Cite as

Safety Profile of Current OA Therapies: Evidence from Clinical Trials

  • Anthony V. Perruccio
  • Vinod Chandran

Key Points

  • The pharmacologic management of osteoarthritis (OA) is primarily targeted at managing symptoms, and there are several classes of agents in current use. Many of these agents, though efficacious, are associated with adverse events.

  • Over time, the complement of adverse events under investigation has broadened, expanding from gastrointestinal (GI) events to also include cardiovascular (CV) and neurological events.

  • Pharmacologic management in OA is challenging, especially in older adults particularly due to comorbidities, different causes of pain, and a high rate of polypharmacy. In addition, while OA is treated as a homogeneous diagnostic category, there is evidence to suggest otherwise. This has implications for the pharmacologic management of OA and design of drug trials.

  • There is significant adverse GI risk associated with nonselective NSAIDs and adverse CV risk associated with both nonselective and selective NSAIDs.

  • While topical NSAIDs appear to have a better safety profile than oral NSAIDS, there can be some risk of GI and CVD adverse events associated with their use.

  • Intra-articular treatment for knee OA is generally associated with risk of mild adverse events of limited duration. However, there is an identified need for studies of longer follow-up with this intervention. With respect to the use of platelet-rich plasma (PRP), it is suggested that the inclusion of leukocytes in the treatment of OA be avoided.

  • Treatment with TNF blockers and IL-1β inhibition is generally well tolerated; majority of adverse events are graded as mild to moderate in severity. Further work with improved study designs is needed.

  • Favorable safety profiles are critical from a clinical perspective. Pragmatic studies that include a wider range of people, including the older age groups with a greater burden of arthritis, are necessary to inform clinical practice.

Keywords

Nonsteroidal anti-inflammatory drugs (NSAIDS) Acetaminophen Opioids Serotonin–norephinephrine reuptake inhibitors (SNRIs) Intra-articular Platelet-rich plasma (PRP) TNF blockers Interleukin 1 beta (IL-1B) inhibition 

References

  1. 1.
    Wielage RC, Myers JA, Klein RW, Happich M. Cost-effectiveness analyses of osteoarthritis oral therapies: a systematic review. Appl Health Econ Health Policy. 2013;11(6):593–618.PubMedGoogle Scholar
  2. 2.
    Maetzel A, Krahn M, Naglie G. The cost effectiveness of rofecoxib and celecoxib in patients with osteoarthritis or rheumatoid arthritis. Arthritis Rheum. 2003;49(3):283–92.PubMedGoogle Scholar
  3. 3.
    Schaefer M, DeLattre M, Gao X, Stephens J, Botteman M, Morreale A. Assessing the cost-effectiveness of COX-2 specific inhibitors for arthritis in the Veterans Health Administration. Curr Med Res Opin. 2005;21(1):47–60.PubMedGoogle Scholar
  4. 4.
    Contreras-Hernandez I, Mould-Quevedo JF, Torres-Gonzalez R, Goycochea-Robles MV, Pacheco-Dominguez RL, Sanchez-Garcia S, et al. Cost-effectiveness analysis for joint pain treatment in patients with osteoarthritis treated at the Instituto Mexicano del Seguro Social (IMSS): comparison of nonsteroidal anti-inflammatory drugs (NSAIDs) vs. cyclooxygenase-2 selective inhibitors. Cost Eff Resour Alloc. 2008;6:21.PubMedCentralPubMedGoogle Scholar
  5. 5.
    McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(3):363–88.PubMedGoogle Scholar
  6. 6.
    Perez GS, Garcia Rodriguez LA, Raiford DS, Duque OA, Ris RJ. Nonsteroidal anti-inflammatory drugs and the risk of hospitalization for acute renal failure. Arch Intern Med. 1996;156(21):2433–9.Google Scholar
  7. 7.
    Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999;340(24):1888–99.PubMedGoogle Scholar
  9. 9.
    Whelton A. Renal aspects of treatment with conventional nonsteroidal anti-inflammatory drugs versus cyclooxygenase-2-specific inhibitors. Am J Med. 2001;110(Suppl 3A):33S–42.PubMedGoogle Scholar
  10. 10.
    Hunt RH, Choquette D, Craig BN, De AC, Habal F, Fulthorpe G, et al. Approach to managing musculoskeletal pain: acetaminophen, cyclooxygenase-2 inhibitors, or traditional NSAIDs? Can Fam Physician. 2007;53(7):1177–84.PubMedCentralPubMedGoogle Scholar
  11. 11.
    U.S. Food and Drug Administration. Public Health Advisory – FDA announces important changes and additional warnings for COX-2 selective and non-selective Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). U.S. Food and Drug Administration, U.S. Department of Health & Human Services, Silver Spring, MD; 2013.Google Scholar
  12. 12.
    Solomon DH, Rassen JA, Glynn RJ, Lee J, Levin R, Schneeweiss S. The comparative safety of analgesics in older adults with arthritis. Arch Intern Med. 2010;170(22):1968–76.PubMedGoogle Scholar
  13. 13.
    Hernandez-Diaz S, Rodriguez LA. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med. 2000;160(14):2093–9.PubMedGoogle Scholar
  14. 14.
    Leontiadis GI, Sreedharan A, Dorward S, Barton P, Delaney B, Howden CW, et al. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding. Health Technol Assess. 2007;11(51):iii–iv, 1–164.PubMedGoogle Scholar
  15. 15.
    Lanas A. A review of the gastrointestinal safety data – a gastroenterologist’s perspective. Rheumatology (Oxford). 2010;49(Suppl 2):ii3–10.Google Scholar
  16. 16.
    Gislason GH, Jacobsen S, Rasmussen JN, Rasmussen S, Buch P, Friberg J, et al. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation. 2006;113(25):2906–13.PubMedGoogle Scholar
  17. 17.
    McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011;8(9), e1001098.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365(9458):475–81.PubMedGoogle Scholar
  19. 19.
    Bak S, Andersen M, Tsiropoulos I, Garcia Rodriguez LA, Hallas J, Christensen K, et al. Risk of stroke associated with nonsteroidal anti-inflammatory drugs: a nested case-control study. Stroke. 2003;34(2):379–86.PubMedGoogle Scholar
  20. 20.
    Schneider V, Levesque LE, Zhang B, Hutchinson T, Brophy JM. Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: a population-based, nested case-control analysis. Am J Epidemiol. 2006;164(9):881–9.PubMedGoogle Scholar
  21. 21.
    Gooch K, Culleton BF, Manns BJ, Zhang J, Alfonso H, Tonelli M, et al. NSAID use and progression of chronic kidney disease. Am J Med. 2007;120(3):280–7.PubMedGoogle Scholar
  22. 22.
    Brater DC. Anti-inflammatory agents and renal function. Semin Arthritis Rheum. 2002;32(3 Suppl 1):33–42.PubMedGoogle Scholar
  23. 23.
    Richy F, Bruyere O, Ethgen O, Rabenda V, Bouvenot G, Audran M, et al. Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach. Ann Rheum Dis. 2004;63(7):759–66.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Schjerning Olsen AM, Fosbol EL, Lindhardsen J, Folke F, Charlot M, Selmer C, et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study. Circulation. 2011;123(20):2226–35.PubMedGoogle Scholar
  25. 25.
    Helin-Salmivaara A, Virtanen A, Vesalainen R, Gronroos JM, Klaukka T, Idanpaan-Heikkila JE, et al. NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland. Eur Heart J. 2006;27(14):1657–63.PubMedGoogle Scholar
  26. 26.
    Gigante A, Tagarro I. Non-steroidal anti-inflammatory drugs and gastroprotection with proton pump inhibitors: a focus on ketoprofen/omeprazole. Clin Drug Investig. 2012;32(4):221–33.PubMedGoogle Scholar
  27. 27.
    Hochberg MC, Fort JG, Svensson O, Hwang C, Sostek M. Fixed-dose combination of enteric-coated naproxen and immediate-release esomeprazole has comparable efficacy to celecoxib for knee osteoarthritis: two randomized trials. Curr Med Res Opin. 2011;27(6):1243–53.PubMedGoogle Scholar
  28. 28.
    Laine L, Kivitz AJ, Bello AE, Grahn AY, Schiff MH, Taha AS. Double-blind randomized trials of single-tablet ibuprofen/high-dose famotidine vs. ibuprofen alone for reduction of gastric and duodenal ulcers. Am J Gastroenterol. 2012;107(3):379–86.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Chen YF, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, et al. Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess. 2008;12(11):1–278, iii.PubMedGoogle Scholar
  30. 30.
    Auriel E, Regev K, Korczyn AD. Nonsteroidal anti-inflammatory drugs exposure and the central nervous system. Handb Clin Neurol. 2014;119:577–84.PubMedGoogle Scholar
  31. 31.
    McElwee NE, Veltri JC, Bradford DC, Rollins DE. A prospective, population-based study of acute ibuprofen overdose: complications are rare and routine serum levels not warranted. Ann Emerg Med. 1990;19(6):657–62.PubMedGoogle Scholar
  32. 32.
    American Geriatrics Society Panel on Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc. 2009;57(8):1331–46.Google Scholar
  33. 33.
    Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet. 2006;368(9549):1771–81.PubMedGoogle Scholar
  34. 34.
    Hinz B, Dormann H, Brune K. More pronounced inhibition of cyclooxygenase 2, increase in blood pressure, and reduction of heart rate by treatment with diclofenac compared with celecoxib and rofecoxib. Arthritis Rheum. 2006;54(1):282–91.PubMedGoogle Scholar
  35. 35.
    Levesque LE, Brophy JM, Zhang B. The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults. Ann Intern Med. 2005;142(7):481–9.PubMedGoogle Scholar
  36. 36.
    Roth SH, Bennett RE. Nonsteroidal anti-inflammatory drug gastropathy. Recognition and response. Arch Intern Med. 1987;147(12):2093–100.PubMedGoogle Scholar
  37. 37.
    Roth SH. Coming to terms with nonsteroidal anti-inflammatory drug gastropathy. Drugs. 2012;72(7):873–9.PubMedGoogle Scholar
  38. 38.
    Turajane T, Wongbunnak R, Patcharatrakul T, Ratansumawong K, Poigampetch Y, Songpatanasilp T. Gastrointestinal and cardiovascular risk of non-selective NSAIDs and COX-2 inhibitors in elderly patients with knee osteoarthritis. J Med Assoc Thai. 2009;92 Suppl 6:S19–26.PubMedGoogle Scholar
  39. 39.
    American Academy of Orthopaedic Surgeons (2013) Treatment of osteoarthritis of the knee evidence-based guideline. Am Acad Orthop Surg. 2. p. 343.Google Scholar
  40. 40.
    Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62(12):1145–55.PubMedCentralPubMedGoogle Scholar
  41. 41.
    National Collaborating Centre for Chronic Conditions. Osteoarthritis: national clinical guideline for care and management in adults. London: Royal College of Physicians; 2008.Google Scholar
  42. 42.
    Zhang W, Doherty M, Arden N, Bannwarth B, Bijlsma J, Gunther KP, et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2005;64(5):669–81.PubMedCentralPubMedGoogle Scholar
  43. 43.
    Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage. 2007;15(9):981–1000.PubMedGoogle Scholar
  44. 44.
    Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16(2):137–62.PubMedGoogle Scholar
  45. 45.
    Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, 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 Res (Hoboken). 2012;64(4):465–74.Google Scholar
  46. 46.
    James LP, Mayeux PR, Hinson JA. Acetaminophen-induced hepatotoxicity. Drug Metab Dispos. 2003;31(12):1499–506.PubMedGoogle Scholar
  47. 47.
    Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage. 2010;18(4):476–99.PubMedGoogle Scholar
  48. 48.
    Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42(6):1364–72.PubMedGoogle Scholar
  49. 49.
    Gyamlani GG, Parikh CR. Acetaminophen toxicity: suicidal vs. accidental. Crit Care. 2002;6(2):155–9.PubMedCentralPubMedGoogle Scholar
  50. 50.
    Schiodt FV, Rochling FA, Casey DL, Lee WM. Acetaminophen toxicity in an urban county hospital. N Engl J Med. 1997;337(16):1112–7.PubMedGoogle Scholar
  51. 51.
    U.S. Food and Drug Administration. FDA drug safety communication: prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning will highlight potential for severe liver failure. U.S. Food and Drug Administration, U.S. Department of Health & Human Services, Silver Spring, MD; 2014.Google Scholar
  52. 52.
    Garcia Rodriguez LA, Hernandez-Diaz S. Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology. 2001;12(5):570–6.PubMedGoogle Scholar
  53. 53.
    Rahme E, Barkun A, Nedjar H, Gaugris S, Watson D. Hospitalizations for upper and lower GI events associated with traditional NSAIDs and acetaminophen among the elderly in Quebec, Canada. Am J Gastroenterol. 2008;103(4):872–82.PubMedGoogle Scholar
  54. 54.
    Chan AT, Manson JE, Albert CM, Chae CU, Rexrode KM, Curhan GC, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation. 2006;113(12):1578–87.PubMedGoogle Scholar
  55. 55.
    Forman JP, Rimm EB, Curhan GC. Frequency of analgesic use and risk of hypertension among men. Arch Intern Med. 2007;167(4):394–9.PubMedGoogle Scholar
  56. 56.
    Curhan GC, Willett WC, Rosner B, Stampfer MJ. Frequency of analgesic use and risk of hypertension in younger women. Arch Intern Med. 2002;162(19):2204–8.PubMedGoogle Scholar
  57. 57.
    Dedier J, Stampfer MJ, Hankinson SE, Willett WC, Speizer FE, Curhan GC. Nonnarcotic analgesic use and the risk of hypertension in US women. Hypertension. 2002;40(5):604–8.PubMedGoogle Scholar
  58. 58.
    U.S. Food and Drug Administration. Limiting acetaminophen’s strength in prescription medicines. U.S. Food and Drug Administration, U.S. Department of Health & Human Services, Silver Spring, MD; 2014.Google Scholar
  59. 59.
    Papaleontiou M, Henderson Jr CR, Turner BJ, Moore AA, Olkhovskaya Y, Amanfo L, et al. Outcomes associated with opioid use in the treatment of chronic noncancer pain in older adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2010;58(7):1353–69.PubMedCentralPubMedGoogle Scholar
  60. 60.
    Avouac J, Gossec L, Dougados M. Efficacy and safety of opioids for osteoarthritis: a meta-analysis of randomized controlled trials. Osteoarthritis Cartilage. 2007;15(8):957–65.PubMedGoogle Scholar
  61. 61.
    da Costa BR, Nuesch E, Kasteler R, Husni E, Welch V, Rutjes AW, et al. Oral or transdermal opioids for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2014;9, CD003115.PubMedGoogle Scholar
  62. 62.
    Silverman SM. Opioid induced hyperalgesia: clinical implications for the pain practitioner. Pain Physician. 2009;12(3):679–84.PubMedGoogle Scholar
  63. 63.
    Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E. Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects. CMAJ. 2006;174(11):1589–94.PubMedCentralPubMedGoogle Scholar
  64. 64.
    McCarberg BH. Pain management in primary care: strategies to mitigate opioid misuse, abuse, and diversion. Postgrad Med. 2011;123(2):119–30.PubMedGoogle Scholar
  65. 65.
    Chappell AS, Ossanna MJ, Liu-Seifert H, Iyengar S, Skljarevski V, Li LC, et al. Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial. Pain. 2009;146(3):253–60.PubMedGoogle Scholar
  66. 66.
    Chappell AS, Desaiah D, Liu-Seifert H, Zhang S, Skljarevski V, Belenkov Y, et al. A double-blind, randomized, placebo-controlled study of the efficacy and safety of duloxetine for the treatment of chronic pain due to osteoarthritis of the knee. Pain Pract. 2011;11(1):33–41.PubMedGoogle Scholar
  67. 67.
    Sullivan M, Bentley S, Fan MY, Gardner G. A single-blind placebo run-in study of venlafaxine XR for activity-limiting osteoarthritis pain. Pain Med. 2009;10(5):806–12.PubMedGoogle Scholar
  68. 68.
    Sullivan MD, Bentley S, Fan MY, Gardner G. A single-blind, placebo run-in study of duloxetine for activity-limiting osteoarthritis pain. J Pain. 2009;10(2):208–13.PubMedGoogle Scholar
  69. 69.
    Conaghan PG, Dickson J, Grant RL. Care and management of osteoarthritis in adults: summary of NICE guidance. BMJ. 2008;336(7642):502–3.PubMedCentralPubMedGoogle Scholar
  70. 70.
    U.S. Food and Drug Administration. FDA clears Cymbalta to treat chronic musculoskeletal pain. U.S. Food and Drug Administration, U.S. Department of Health & Human Services, Silver Spring, MD; 2013.Google Scholar
  71. 71.
    Frakes EP, Risser RC, Ball TD, Hochberg MC, Wohlreich MM. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. Curr Med Res Opin. 2011;27(12):2361–72.PubMedGoogle Scholar
  72. 72.
    Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112–20.PubMedGoogle Scholar
  73. 73.
    Vuppalanchi R, Hayashi PH, Chalasani N, Fontana RJ, Bonkovsky H, Saxena R, et al. Duloxetine hepatotoxicity: a case-series from the drug-induced liver injury network. Aliment Pharmacol Ther. 2010;32(9):1174–83.PubMedCentralPubMedGoogle Scholar
  74. 74.
    Kuehn BM. Serotonin syndrome update. JAMA. 2011;306(24):2661.Google Scholar
  75. 75.
    Arnstein PM. Evolution of topical NSAIDs in the guidelines for treatment of osteoarthritis in elderly patients. Drugs Aging. 2012;29(7):523–31.PubMedGoogle Scholar
  76. 76.
    Altman RD. New guidelines for topical NSAIDs in the osteoarthritis treatment paradigm. Curr Med Res Opin. 2010;26(12):2871–6.PubMedGoogle Scholar
  77. 77.
    Baraf HS, Gloth FM, Barthel HR, Gold MS, Altman RD. Safety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in elderly and younger patients: pooled data from three randomized, double-blind, parallel-group, placebo-controlled, multicentre trials. Drugs Aging. 2011;28(1):27–40.PubMedGoogle Scholar
  78. 78.
    Haroutiunian S, Drennan DA, Lipman AG. Topical NSAID therapy for musculoskeletal pain. Pain Med. 2010;11(4):535–49.PubMedGoogle Scholar
  79. 79.
    Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. BMJ. 2004;329(7461):324.PubMedCentralPubMedGoogle Scholar
  80. 80.
    Friedman PM, Mafong EA, Friedman ES, Geronemus RG. Topical anesthetics update: EMLA and beyond. Dermatol Surg. 2001;27(12):1019–26.PubMedGoogle Scholar
  81. 81.
    Tugwell PS, Wells GA, Shainhouse JZ. Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. J Rheumatol. 2004;31(10):2002–12.PubMedGoogle Scholar
  82. 82.
    Heyneman CA, Lawless-Liday C, Wall GC. Oral versus topical NSAIDs in rheumatic diseases: a comparison. Drugs. 2000;60(3):555–74.PubMedGoogle Scholar
  83. 83.
    Jorge LL, Feres CC, Teles VE. Topical preparations for pain relief: efficacy and patient adherence. J Pain Res. 2011;4:11–24.PubMedCentralGoogle Scholar
  84. 84.
    Altman RD, Barthel HR. Topical therapies for osteoarthritis. Drugs. 2011;71(10):1259–79.PubMedGoogle Scholar
  85. 85.
    Makris UE, Kohler MJ, Fraenkel L. Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. J Rheumatol. 2010;37(6):1236–43.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Roth SH, Fuller P. Diclofenac topical solution compared with oral diclofenac: a pooled safety analysis. J Pain Res. 2011;4:159–67.PubMedCentralPubMedGoogle Scholar
  87. 87.
    Simon LS, Grierson LM, Naseer Z, Bookman AA, Zev SJ. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain. 2009;143(3):238–45.PubMedGoogle Scholar
  88. 88.
    U.S. Food and Drug Administration. Voltaren Gel (diclofenac sodium topical gel) 1% – hepatic effects labeling changes. U.S. Food and Drug Administration, U.S. Department of Health & Human Services, Silver Spring, MD; 2013.Google Scholar
  89. 89.
    Laslett LL, Jones G. Capsaicin for osteoarthritis pain. Prog Drug Res. 2014;68:277–91.PubMedGoogle Scholar
  90. 90.
    Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;2, CD005328.PubMedGoogle Scholar
  91. 91.
    Atchia I, Kane D, Reed MR, Isaacs JD, Birrell F. Efficacy of a single ultrasound-guided injection for the treatment of hip osteoarthritis. Ann Rheum Dis. 2011;70(1):110–6.PubMedGoogle Scholar
  92. 92.
    Heyworth BE, Lee JH, Kim PD, Lipton CB, Strauch RJ, Rosenwasser MP. Hylan versus corticosteroid versus placebo for treatment of basal joint arthritis: a prospective, randomized, double-blinded clinical trial. J Hand Surg Am. 2008;33(1):40–8.PubMedGoogle Scholar
  93. 93.
    Shimizu M, Higuchi H, Takagishi K, Shinozaki T, Kobayashi T. Clinical and biochemical characteristics after intra-articular injection for the treatment of osteoarthritis of the knee: prospective randomized study of sodium hyaluronate and corticosteroid. J Orthop Sci. 2010;15(1):51–6.PubMedGoogle Scholar
  94. 94.
    Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;2, CD005321.PubMedGoogle Scholar
  95. 95.
    Rutjes AW, Juni P, da Costa BR, Trelle S, Nuesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med. 2012;157(3):180–91.PubMedGoogle Scholar
  96. 96.
    McAlindon TE, Bannuru RR. Osteoarthritis: is viscosupplementation really so unsafe for knee OA? Nat Rev Rheumatol. 2012;8(11):635–6.PubMedGoogle Scholar
  97. 97.
    Miller LE, Block JE. US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: systematic review and meta-analysis of randomized, saline-controlled trials. Clin Med Insights Arthritis Musculoskelet Disord. 2013;6:57–63.PubMedCentralPubMedGoogle Scholar
  98. 98.
    Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews. US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: systematic review and meta-analysis of randomized, saline-controlled trials. Centre for Reviews and Dissemination, University of York, UK; 2014.Google Scholar
  99. 99.
    Bannuru RR, Vaysbrot EE, Sullivan MC, McAlindon TE. Relative efficacy of hyaluronic acid in comparison with NSAIDs for knee osteoarthritis: a systematic review and meta-analysis. Semin Arthritis Rheum. 2014;43(5):593–9.PubMedGoogle Scholar
  100. 100.
    Garcia Rodriguez LA, Gonzalez-Perez A. Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population. BMC Med. 2005;3:17.PubMedCentralPubMedGoogle Scholar
  101. 101.
    Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006;332(7553):1302–8.PubMedCentralPubMedGoogle Scholar
  102. 102.
    O’Neil CK, Hanlon JT, Marcum ZA. Adverse effects of analgesics commonly used by older adults with osteoarthritis: focus on non-opioid and opioid analgesics. Am J Geriatr Pharmacother. 2012;10(6):331–42.PubMedCentralPubMedGoogle Scholar
  103. 103.
    Chang KV, Hsiao MY, Chen WS, Wang TG, Chien KL. Effectiveness of intra-articular hyaluronic acid for ankle osteoarthritis treatment: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2013;94(5):951–60.PubMedGoogle Scholar
  104. 104.
    Cohen MM, Altman RD, Hollstrom R, Hollstrom C, Sun C, Gipson B. Safety and efficacy of intra-articular sodium hyaluronate (Hyalgan) in a randomized, double-blind study for osteoarthritis of the ankle. Foot Ankle Int. 2008;29(7):657–63.PubMedGoogle Scholar
  105. 105.
    DeGroot III H, Uzunishvili S, Weir R, Al-omari A, Gomes B. Intra-articular injection of hyaluronic acid is not superior to saline solution injection for ankle arthritis: a randomized, double-blind, placebo-controlled study. J Bone Joint Surg Am. 2012;94(1):2–8.PubMedGoogle Scholar
  106. 106.
    Luciani D, Cadossi M, Tesei F, Chiarello E, Giannini S. Viscosupplementation for grade II osteoarthritis of the ankle: a prospective study at 18 months’ follow-up. Chir Organi Mov. 2008;92(3):155–60.PubMedGoogle Scholar
  107. 107.
    Salk RS, Chang TJ, D’Costa WF, Soomekh DJ, Grogan KA. Sodium hyaluronate in the treatment of osteoarthritis of the ankle: a controlled, randomized, double-blind pilot study. J Bone Joint Surg Am. 2006;88(2):295–302.PubMedGoogle Scholar
  108. 108.
    Witteveen AG, Giannini S, Guido G, Jerosch J, Lohrer H, Vannini F, et al. A prospective multi-centre, open study of the safety and efficacy of hylan G-F 20 (Synvisc) in patients with symptomatic ankle (talo-crural) osteoarthritis. Foot Ankle Surg. 2008;14(3):145–52.PubMedGoogle Scholar
  109. 109.
    Carpenter B, Motley T. The role of viscosupplementation in the ankle using hylan G-F 20. J Foot Ankle Surg. 2008;47(5):377–84.PubMedGoogle Scholar
  110. 110.
    Reichenbach S, Blank S, Rutjes AW, Shang A, King EA, Dieppe PA, et al. Hylan versus hyaluronic acid for osteoarthritis of the knee: a systematic review and meta-analysis. Arthritis Rheum. 2007;57(8):1410–8.PubMedGoogle Scholar
  111. 111.
    Colen S, van den Bekerom MP, Mulier M, Haverkamp D. Hyaluronic acid in the treatment of knee osteoarthritis: a systematic review and meta-analysis with emphasis on the efficacy of different products. BioDrugs. 2012;26(4):257–68.PubMedGoogle Scholar
  112. 112.
    Colen S, Haverkamp D, Mulier M, van den Bekerom MP. Hyaluronic acid for the treatment of osteoarthritis in all joints except the knee: what is the current evidence? BioDrugs. 2012;26(2):101–12.PubMedGoogle Scholar
  113. 113.
    Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41(2):356–64.PubMedGoogle Scholar
  114. 114.
    Filardo G, Kon E, Di MA, Di MB, Merli ML, Cenacchi A, et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord. 2012;13:229.PubMedCentralPubMedGoogle Scholar
  115. 115.
    Anitua E, Sanchez M, Aguirre JJ, Prado R, Padilla S, Orive G. Efficacy and safety of plasma rich in growth factors intra-articular infiltrations in the treatment of knee osteoarthritis. Arthroscopy. 2014;30(8):1006–17.PubMedGoogle Scholar
  116. 116.
    Filardo G, Kon E, Pereira Ruiz MT, Vaccaro F, Guitaldi R, Di MA, et al. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012;20(10):2082–91.PubMedGoogle Scholar
  117. 117.
    Sanchez M, Fiz N, Azofra J, Usabiaga J, Aduriz RE, Garcia GA, et al. A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy. 2012;28(8):1070–8.PubMedGoogle Scholar
  118. 118.
    Vaquerizo V, Plasencia MA, Arribas I, Seijas R, Padilla S, Orive G, et al. Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial. Arthroscopy. 2013;29(10):1635–43.PubMedGoogle Scholar
  119. 119.
    Sanchez M, Anitua E, Azofra J, Aguirre JJ, Andia I. Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee OA: a retrospective cohort study. Clin Exp Rheumatol. 2008;26(5):910–3.PubMedGoogle Scholar
  120. 120.
    Say F, Gurler D, Yener K, Bulbul M, Malkoc M. Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis. Acta Chir Orthop Traumatol Cech. 2013;80(4):278–83.PubMedGoogle Scholar
  121. 121.
    Anitua E, Sanchez M, Prado R, Orive G. The type of platelet-rich plasma may influence the safety of the approach. Knee Surg Sports Traumatol Arthrosc. 2014;22(7):1708–9.PubMedGoogle Scholar
  122. 122.
    Anitua E, Sanchez M, Orive G, Padilla S. A biological therapy to osteoarthritis treatment using platelet-rich plasma. Expert Opin Biol Ther. 2013;13(8):1161–72.PubMedGoogle Scholar
  123. 123.
    McCarrel TM, Minas T, Fortier LA. Optimization of leukocyte concentration in platelet-rich plasma for the treatment of tendinopathy. J Bone Joint Surg Am. 2012;94(19):e143–8.PubMedGoogle Scholar
  124. 124.
    Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39(10):2135–40.PubMedGoogle Scholar
  125. 125.
    Reginster JY, Badurski J, Bellamy N, Bensen W, Chapurlat R, Chevalier X, et al. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial. Ann Rheum Dis. 2013;72(2):179–86.PubMedCentralPubMedGoogle Scholar
  126. 126.
    Reginster JY. Response to Dr Bolland’s eLetter: strontium and cardiovascular events. Ann Rheum Dis. 2014;73(2), e9.PubMedGoogle Scholar
  127. 127.
    European Medicines Agency. Recommendation to restrict the use of Protelos/Osseor (strontium ranelate). European Medicines Agency, London, UK; 2013.Google Scholar
  128. 128.
    Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL, Smith MD, et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med. 2010;363(16):1521–31.PubMedGoogle Scholar
  129. 129.
    Nagashima H, Suzuki M, Araki S, Yamabe T, Muto C. Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study. Osteoarthritis Cartilage. 2011;19(12):1405–12.PubMedGoogle Scholar
  130. 130.
    Schnitzer TJ, Lane NE, Birbara C, Smith MD, Simpson SL, Brown MT. Long-term open-label study of tanezumab for moderate to severe osteoarthritic knee pain. Osteoarthritis Cartilage. 2011;19(6):639–46.PubMedGoogle Scholar
  131. 131.
    Spierings EL, Fidelholtz J, Wolfram G, Smith MD, Brown MT, West CR. A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee. Pain. 2013;154(9):1603–12.PubMedGoogle Scholar
  132. 132.
    Seidel MF, Lane NE. Control of arthritis pain with anti-nerve-growth factor: risk and benefit. Curr Rheumatol Rep. 2012;14(6):583–8.PubMedGoogle Scholar
  133. 133.
    Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR. Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial. J Pain. 2012;13(8):790–8.PubMedGoogle Scholar
  134. 134.
    Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR. Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind, placebo-controlled phase III trial. Arthritis Rheum. 2013;65(7):1795–803.PubMedGoogle Scholar
  135. 135.
    Pfizer Inc. Tanezumab Arthritis Advisory Committee briefing document. U.S. Food and Drug Administration, Silver Spring, MD; 2012.Google Scholar
  136. 136.
    Spierings EL, Fidelholtz J, Wolfram G, Smith MD, Brown MT, West CR. A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee: response to letter to the editor. Pain. 2014;155(11):2432–3.Google Scholar
  137. 137.
    Panzram B, Schiltenwolf M. Pain therapy with high risk: one-sided presentation of the results from the latest phase III study on tanezumab in osteoarthritis pain. Pain. 2014;155(11):2432.PubMedGoogle Scholar
  138. 138.
    Magnano MD, Chakravarty EF, Broudy C, Chung L, Kelman A, Hillygus J, et al. A pilot study of tumor necrosis factor inhibition in erosive/inflammatory osteoarthritis of the hands. J Rheumatol. 2007;34(6):1323–7.PubMedGoogle Scholar
  139. 139.
    Verbruggen G, Wittoek R, Vander CB, Elewaut D. Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification. Ann Rheum Dis. 2012;71(6):891–8.PubMedCentralPubMedGoogle Scholar
  140. 140.
    Maksymowych WP, Russell AS, Chiu P, Yan A, Jones N, Clare T, et al. Targeting tumour necrosis factor alleviates signs and symptoms of inflammatory osteoarthritis of the knee. Arthritis Res Ther. 2012;14(5):R206.PubMedCentralPubMedGoogle Scholar
  141. 141.
    Chevalier X, Ravaud P, Maheu E, Baron G, Rialland A, Vergnaud P, et al. Adalimumab in patients with hand osteoarthritis refractory to analgesics and NSAIDs: a randomised, multicentre, double-blind, placebo-controlled trial. Ann Rheum Dis. 2014. doi:10.1136/annrheumdis-2014-205348. [Epub ahead of print].
  142. 142.
    Chevalier X, Giraudeau B, Conrozier T, Marliere J, Kiefer P, Goupille P. Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study. J Rheumatol. 2005;32(7):1317–23.PubMedGoogle Scholar
  143. 143.
    Chevalier X, Goupille P, Beaulieu AD, Burch FX, Bensen WG, Conrozier T, et al. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2009;61(3):344–52.PubMedGoogle Scholar
  144. 144.
    Cohen SB, Proudman S, Kivitz AJ, Burch FX, Donohue JP, Burstein D, et al. A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee. Arthritis Res Ther. 2011;13(4):R125.PubMedCentralPubMedGoogle Scholar
  145. 145.
    Perucca E. Age-related changes in pharmacokinetics: predictability and assessment methods. Int Rev Neurobiol. 2007;81:183–99.PubMedGoogle Scholar
  146. 146.
    Schmucker DL. Liver function and phase I drug metabolism in the elderly: a paradox. Drugs Aging. 2001;18(11):837–51.PubMedGoogle Scholar
  147. 147.
    Wynne H. Drug metabolism and ageing. J Br Menopause Soc. 2005;11(2):51–6.PubMedGoogle Scholar
  148. 148.
    Arnstein P. Balancing analgesic efficacy with safety concerns in the older patient. Pain Manag Nurs. 2010;11(2 Suppl):S11–22.PubMedGoogle Scholar
  149. 149.
    van Dijk GM, Veenhof C, Schellevis F, Hulsmans H, Bakker JP, Arwert H, et al. Comorbidity, limitations in activities and pain in patients with osteoarthritis of the hip or knee. BMC Musculoskelet Disord. 2008;9:95.PubMedCentralPubMedGoogle Scholar
  150. 150.
    Kadam UT, Jordan K, Croft PR. Clinical comorbidity in patients with osteoarthritis: a case-control study of general practice consulters in England and Wales. Ann Rheum Dis. 2004;63(4):408–14.PubMedCentralPubMedGoogle Scholar
  151. 151.
    Hoogeboom TJ, den Broeder AA, Swierstra BA, de Bie RA, van den Ende CH. Joint-pain comorbidity, health status, and medication use in hip and knee osteoarthritis: a cross-sectional study. Arthritis Care Res (Hoboken). 2012;64(1):54–8.Google Scholar
  152. 152.
    Perruccio AV, Power JD, Evans HM, Mahomed SR, Gandhi R, Mahomed NN, et al. Multiple joint involvement in total knee replacement for osteoarthritis: effects on patient-reported outcomes. Arthritis Care Res (Hoboken). 2012;64(6):838–46.Google Scholar
  153. 153.
    Slater M, Perruccio AV, Badley EM. Musculoskeletal comorbidities in cardiovascular disease, diabetes and respiratory disease: the impact on activity limitations; a representative population-based study. BMC Public Health. 2011;11:77.PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Arthritis Program and Toronto Western Research InstituteToronto Western Hospital, University Health NetworkTorontoCanada
  2. 2.Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public HealthTorontoCanada
  3. 3.Department of Surgery, Faculty of MedicineUniversity of TorontoTorontoCanada
  4. 4.Division of Rheumatology, Department of Medicine, Faculty of MedicineUniversity of TorontoTorontoCanada
  5. 5.Centre for Prognosis Studies in the Rheumatic DiseasesToronto Western Research InstituteTorontoCanada
  6. 6.Institute of Medical ScienceUniversity of TorontoTorontoCanada

Personalised recommendations