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01-01-2015 | Osteoarthritis | Book Chapter | Article

11. Safety Profile of Current OA Therapies: Evidence from Clinical Trials

Authors: Anthony V. Perruccio, PhD, Vinod Chandran, MBBS, MD, DM, PhD

Publisher: Springer International Publishing

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Abstract

  • 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.
Literature
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.PubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMed
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.
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.PubMedCentralPubMed
8.
Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999;340(24):1888–99.PubMed
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.PubMed
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.PubMedCentralPubMed
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.
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.PubMed
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.PubMed
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.PubMed
15.
Lanas A. A review of the gastrointestinal safety data – a gastroenterologist’s perspective. Rheumatology (Oxford). 2010;49(Suppl 2):ii3–10.
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.PubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
22.
Brater DC. Anti-inflammatory agents and renal function. Semin Arthritis Rheum. 2002;32(3 Suppl 1):33–42.PubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMed
30.
Auriel E, Regev K, Korczyn AD. Nonsteroidal anti-inflammatory drugs exposure and the central nervous system. Handb Clin Neurol. 2014;119:577–84.PubMed
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.PubMed
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.
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.PubMed
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.PubMed
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.PubMed
36.
Roth SH, Bennett RE. Nonsteroidal anti-inflammatory drug gastropathy. Recognition and response. Arch Intern Med. 1987;147(12):2093–100.PubMed
37.
Roth SH. Coming to terms with nonsteroidal anti-inflammatory drug gastropathy. Drugs. 2012;72(7):873–9.PubMed
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.PubMed
39.
American Academy of Orthopaedic Surgeons (2013) Treatment of osteoarthritis of the knee evidence-based guideline. Am Acad Orthop Surg. 2. p. 343.
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.PubMedCentralPubMed
41.
National Collaborating Centre for Chronic Conditions. Osteoarthritis: national clinical guideline for care and management in adults. London: Royal College of Physicians; 2008.
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.
46.
James LP, Mayeux PR, Hinson JA. Acetaminophen-induced hepatotoxicity. Drug Metab Dispos. 2003;31(12):1499–506.PubMed
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.PubMed
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.PubMed
49.
Gyamlani GG, Parikh CR. Acetaminophen toxicity: suicidal vs. accidental. Crit Care. 2002;6(2):155–9.PubMedCentralPubMed
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.PubMed
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.
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.
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.PubMedCentralPubMed
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.PubMed
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.PubMed
62.
Silverman SM. Opioid induced hyperalgesia: clinical implications for the pain practitioner. Pain Physician. 2009;12(3):679–84.PubMed
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.PubMedCentralPubMed
64.
McCarberg BH. Pain management in primary care: strategies to mitigate opioid misuse, abuse, and diversion. Postgrad Med. 2011;123(2):119–30.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
69.
Conaghan PG, Dickson J, Grant RL. Care and management of osteoarthritis in adults: summary of NICE guidance. BMJ. 2008;336(7642):502–3.PubMedCentralPubMed
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.
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.PubMed
72.
Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112–20.PubMed
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.PubMedCentralPubMed
74.
Kuehn BM. Serotonin syndrome update. JAMA. 2011;306(24):2661.
75.
Arnstein PM. Evolution of topical NSAIDs in the guidelines for treatment of osteoarthritis in elderly patients. Drugs Aging. 2012;29(7):523–31.PubMed
76.
Altman RD. New guidelines for topical NSAIDs in the osteoarthritis treatment paradigm. Curr Med Res Opin. 2010;26(12):2871–6.PubMed
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.PubMed
78.
Haroutiunian S, Drennan DA, Lipman AG. Topical NSAID therapy for musculoskeletal pain. Pain Med. 2010;11(4):535–49.PubMed
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.PubMedCentralPubMed
80.
Friedman PM, Mafong EA, Friedman ES, Geronemus RG. Topical anesthetics update: EMLA and beyond. Dermatol Surg. 2001;27(12):1019–26.PubMed
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.PubMed
82.
Heyneman CA, Lawless-Liday C, Wall GC. Oral versus topical NSAIDs in rheumatic diseases: a comparison. Drugs. 2000;60(3):555–74.PubMed
83.
Jorge LL, Feres CC, Teles VE. Topical preparations for pain relief: efficacy and patient adherence. J Pain Res. 2011;4:11–24.PubMedCentral
84.
Altman RD, Barthel HR. Topical therapies for osteoarthritis. Drugs. 2011;71(10):1259–79.PubMed
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.PubMedCentralPubMed
86.
Roth SH, Fuller P. Diclofenac topical solution compared with oral diclofenac: a pooled safety analysis. J Pain Res. 2011;4:159–67.PubMedCentralPubMed
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.PubMed
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.
89.
Laslett LL, Jones G. Capsaicin for osteoarthritis pain. Prog Drug Res. 2014;68:277–91.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
96.
McAlindon TE, Bannuru RR. Osteoarthritis: is viscosupplementation really so unsafe for knee OA? Nat Rev Rheumatol. 2012;8(11):635–6.PubMed
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.PubMedCentralPubMed
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.
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.PubMed
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.PubMedCentralPubMed
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.PubMedCentralPubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
126.
Reginster JY. Response to Dr Bolland’s eLetter: strontium and cardiovascular events. Ann Rheum Dis. 2014;73(2), e9.PubMed
127.
European Medicines Agency. Recommendation to restrict the use of Protelos/Osseor (strontium ranelate). European Medicines Agency, London, UK; 2013.
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
135.
Pfizer Inc. Tanezumab Arthritis Advisory Committee briefing document. U.S. Food and Drug Administration, Silver Spring, MD; 2012.
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.
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMedCentralPubMed
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.
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.PubMed
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.PubMed
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.PubMedCentralPubMed
145.
Perucca E. Age-related changes in pharmacokinetics: predictability and assessment methods. Int Rev Neurobiol. 2007;81:183–99.PubMed
146.
Schmucker DL. Liver function and phase I drug metabolism in the elderly: a paradox. Drugs Aging. 2001;18(11):837–51.PubMed
147.
Wynne H. Drug metabolism and ageing. J Br Menopause Soc. 2005;11(2):51–6.PubMed
148.
Arnstein P. Balancing analgesic efficacy with safety concerns in the older patient. Pain Manag Nurs. 2010;11(2 Suppl):S11–22.PubMed
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.PubMedCentralPubMed
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.PubMedCentralPubMed
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.
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.
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.PubMedCentralPubMed
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