Drug-free gel containing ultra-deformable phospholipid vesicles (TDT 064) as topical therapy for the treatment of pain associated with osteoarthritis: a review of clinical efficacy and safety

References

• Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2163-96
   PubMed Web of Science ®Google Scholar
• Jinks C, Jordan K, Croft P. Osteoarthritis as a public health problem: the impact of developing knee pain on physical function in adults living in the community: (KNEST 3). Rheumatology (Oxford) 2007;46:877-81
   PubMed Web of Science ®Google Scholar
• Le TK, Montejano LB, Cao Z, et al. Health care costs in US patients with and without a diagnosis of osteoarthritis. J Pain Res 2012;5:23-30
   PubMedGoogle Scholar
• Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet 2011;377:2115-26
   PubMed Web of Science ®Google Scholar
• Hochberg MC, Altman RD, April KT, 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;64:465-74
   PubMed Web of Science ®Google Scholar
• National Institute of Clinical Excellence. Osteoarthritis: the care and management of osteoarthritis in adults CG59, 2008. Available at: http://publications.nice.org.uk/osteoarthritis-cg59/guidance [Last accessed 19 August 2013]
   Google Scholar
• Richmond J, Hunter D, Irrgang J, et al. American Academy of Orthopaedic Surgeons clinical practice guideline on the treatment of osteoarthritis (OA) of the knee. J Bone Joint Surg Am 2010;92:990-3
   PubMed Web of Science ®Google Scholar
• Zhang W, Nuki G, Moskowitz RW, 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;18:476-99
   PubMed Web of Science ®Google Scholar
• Gore M, Sadosky A, Leslie D, et al. Patterns of therapy switching, augmentation, and discontinuation after initiation of treatment with select medications in patients with osteoarthritis. Clin Ther 2011;33:1914-31
   PubMed Web of Science ®Google Scholar
• 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;10:331-42
   PubMed Web of Science ®Google Scholar
• Coxib and Traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013;382:769-79
   Google Scholar
• Fosbøl EL, Gislason GH, Jacobsen S, et al. Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study. Clin Pharmacol Ther 2009;85:190-7
   PubMed Web of Science ®Google Scholar
• Gislason GH, Jacobsen S, Rasmussen JN, 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;113:2906-13
   PubMed Web of Science ®Google Scholar
• McGettigan P, Henry H. Use of non-steroidal anti-inflammatory drugs that elevate cardiovascular risk: an examination of sales and essential medicines in low-, middle-, and high-income countries. PLoS Med 2013;10:e1001388
   PubMed Web of Science ®Google Scholar
• Akarca US. Gastrointestinal effects of selective and non-selective non-steroidal anti-inflammatory drugs. Curr Pharm Des 2005;11:1779-93
   PubMed Web of Science ®Google Scholar
• Wang X, Tian HJ, Yang HK, et al. Meta-analysis: cyclooxygenase-2 inhibitors are no better than nonselective nonsteroidal anti-inflammatory drugs with proton pump inhibitors in regard to gastrointestinal adverse events in osteoarthritis and rheumatoid arthritis. Eur J Gastroenterol Hepatol 2011;23:876-80
   PubMed Web of Science ®Google Scholar
• Lanas A, Garcia-Tell G, Armada B, et al. Prescription patterns and appropriateness of NSAID therapy according to gastrointestinal risk and cardiovascular history in patients with diagnoses of osteoarthritis. BMC Med 2011;9:38
   PubMed Web of Science ®Google Scholar
• Chan FK, Abraham NS, Scheiman JM, et al. Management of patients on nonsteroidal anti-inflammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents. Am J Gastroenterol 2008;103:2908-18
   PubMed Web of Science ®Google Scholar
• Lanza FL, Chan FK, Quigley EM. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol 2009;104:728-38
   PubMed Web of Science ®Google Scholar
• Van de Werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart 2008;29:2909-45
   PubMed Web of Science ®Google Scholar
• Electronic Medicines Compendium. Celebrex Summary of Product Characteristics, 2011. Available at: http://www.medicines.org.uk/emc/medicine/14534 [Last accessed 19 August 2013]
   Google Scholar
• Electronic Medicines Compendium. Naproxen Summary of Product Characteristics, 2011. Available at: http://www.medicines.org.uk/emc/medicine/23037 [Last accessed 19 August 2013]
   Google Scholar
• Kingsbury SR, Hensor EMA, Walsh CAE, et al. How do people with knee osteoarthritis use osteoarthritis pain medications and does this change over time? Data from the Osteoarthritis Initiative. Arthritis Res Ther 2013;15:R106 . [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Adams RJ, Appleton SL, Gill TK, et al. Cause for concern in the use of non-steroidal anti-inflammatory medications in the community – a population-based study. BMC Fam Pract 2011;12:70
   PubMedGoogle Scholar
• Roumie CL, Arbogast PG, Mitchel EF Jr, et al. Prescriptions for chronic high-dose cyclooxygenase-2 inhibitors are often inappropriate and potentially dangerous. J Gen Intern Med 2005;20:879-83
   PubMed Web of Science ®Google Scholar
• Derry S, Moore RA, Rabbie R. Topical NSAIDs for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev 2012;9:CD007400
   PubMed Web of Science ®Google Scholar
• Heyneman CA, Lawless-Liday C, Wall GC. Oral versus topical NSAID’s in rheumatic diseases. Drugs 2000;60:555-74
   PubMed Web of Science ®Google Scholar
• 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;37:1236-43
   PubMed Web of Science ®Google Scholar
• Rother M, Lavins BJ, Kneer W, et al. Efficacy and safety of epicutaneous ketoprofen in Transfersome (IDEA-033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial. Ann Rheum Dis 2007;66:1178-83
   PubMed Web of Science ®Google Scholar
• Kneer W, Seidel EJ, Mazgareanu S, et al. A 12-week placebo controlled randomized study of topical therapy with three dosages of ketoprofen in Transfersome® gel, compared with ketoprofen-free Transfersome® gel in patients with osteoarthritis of the knee. J Pain Res 2013;6:743-53
   Google Scholar
• Rother M, Mazgareanu S, Vierl U, et al. Impact of investigational site quality on the outcome of clinical studies in osteoarthritis of the knee. Ann Rheum Dis 2009;68:Abstract no. 0360
   Google Scholar
• Rother M, Yeoman G, Ekman E. A double-blind, placebo-controlled trial comparing the safety and efficacy of epicutaneously applied ketoprofen in Transfersome gel with naproxen for the treatment of pain associated with osteoarthritis (OA) of the knee. Ann Rheum Dis 2012;71:Abstract no. EULAR12-3375
   Google Scholar
• Conaghan P, Dickson JD, Bolten W, et al. A multicenter, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis. Rheumatology 2013;52:1303-12
   PubMed Web of Science ®Google Scholar
• Rother M, Conaghan PG. A randomized, double-blind, phase III trial in moderate osteoarthritis knee pain comparing topical ketoprofen gel with ketoprofen-free gel. J Rheumatology 2013;40:1742-48
   PubMed Web of Science ®Google Scholar
• Rother M, Yeoman G, Ekman E. Safety and efficacy of epicutaneously applied Ketoprofen in Transfersome® (IDEA-033) as compared to oral naproxen after 52 weeks of treatment in patients with osteoarthritis (OA) of the knee. Arthritis Rheum 2008;58:Abstract no. 854
   Google Scholar
• Baverstock N. Manager, Preclinical Assessments Sequessome Technology®. Personal Communication. 1 November 2013
   Google Scholar
• Luger T, Rother M. Both ketoprofen in transfersome (IDEA-070) and drug-free vehicle (TDT 070) improved symptoms in patients with inflammatory skin diseases. J Invest Dermatol 2013;133(Suppl 1):S163
   Google Scholar
• Kneer W, Rother I, Rother M, et al. A multiple-dose, open-label, safety, compliance, and usage evaluation study of epicutaneously applied Diractin (ketoprofen in Transfersome) in joint/musculoskeletal pain or soft tissue inflammation. Curr Drug Saf 2009;4:5-10
   PubMedGoogle Scholar
• Rother I, Kneer W, Rother M, Seidel EJ; for the IDEA-033 III-01 Study Group. A multiple-dose, open-label, safety, compliance, and usage evaluating study of epicutaneously applied Diractin® (ketoprofen in Transfersome®) in joint/musculoskeletal pain or soft tissue inflammation. Ninth European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Abstract no. P176
   Google Scholar
• Rother M. Clobetasol solution, clobetasol in transfersome (IDEA-068) and the drug-free vehicle (TDT 068) all showed significant treatment effects in a randomised psoriasis plaque study. J Invest Dermatol 2013;133(Suppl 1):S163
   Google Scholar
• Sigurgeirsson B, Ghannoum M. Therapeutic potential of TDT 067 (terbinafine in Transfersome®): a carrier-based dosage form of terbinafine for onychomycosis. Expert Opin Investig Drugs 2012;21:1549-62
   PubMed Web of Science ®Google Scholar
• Scientific Report no. SP-033-09-013. IDEA AG
   Google Scholar
• Cevc G, Vierl U. Nanotechnology and the transdermal route: a state of the art review and critical appraisal. J Control Release 2010;141:277-99
   PubMed Web of Science ®Google Scholar
• Cevc G, Gebauer D. Hydration-driven transport of deformable lipid vesicles through fine pores and the skin barrier. Biophys J 2003;84:1010-24
   PubMed Web of Science ®Google Scholar
• Barenholz Y, Cevc G. Structure and properties of membranes. In: Baskin A, Norde W (eds.) Physical Chemistry of Biological Surfaces. New York: Marcel Dekker, 2000:171-241
   Google Scholar
• Hills BA. Oligolamellar lubrication of joints by surface active phospholipid. J Rheumatol 1989;16:82-91
   PubMed Web of Science ®Google Scholar
• Hills BA. Remarkable anti-wear properties of joint surfactant. Annals Biomed Eng 1995;23:112-7
   PubMed Web of Science ®Google Scholar
• Hills BA, Monds MK. Deficiency of lubricating surfactant lining the articular surfaces of replaced hips and knees. Br J Rheumatol 1998;37:143-7
   PubMedGoogle Scholar
• Rabinowitz JL, Gregg JR, Nixon JE. Lipid composition of the tissues of human knee joints. II Synovial fluid in trauma. Clin Orthop 1984;190:292-8
   PubMedGoogle Scholar
• Vecchio P, Thomas R, Hills BA. Surfactant treatment for osteoarthritis. Rheumatology (Oxford) 1999;38:1020-1
   PubMed Web of Science ®Google Scholar
• Sivan S, Schroeder A, Verberne G, et al. Liposomes act as effective biolubricants for friction reduction in human synovial joints. Langmuir 2010;26:1107-16
   PubMed Web of Science ®Google Scholar
• Hakshur K, Benhar I, Bar-Ziv Y, et al. The effect of hyaluronan injections into human knees on the number of bone and cartilage wear particles captured by bio-ferrography. Acta Biomater 2011;7:848-57
   PubMed Web of Science ®Google Scholar
• Cevc G, Vierl U, Mazgareanu S. Functional characterisation of novel analgesic product based on self-regulating drug carriers. Int J Pharm 2008;360:18-28
   PubMed Web of Science ®Google Scholar
• Cevc G, Mazgareanu S, Rother M. Preclinical characterisation of NSAIDs in ultradeformable carriers or conventional topical gels. Int J Pharmaceutics 2008;360:29-39
   PubMed Web of Science ®Google Scholar
• Cevc G, Schätzlein A, Richardsen H. Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Evidence from double label CLSM experiments and direct size measurements. Biochim Biophys Acta 2002;1564:21-30
   PubMed Web of Science ®Google Scholar
• Bensen WG, Fiechtner JJ, McMillen JI, et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc 1999;74:1095-105
   PubMed Web of Science ®Google Scholar
• Moskowitz RW, Sunshine A, Brugger A, et al. American pain society pain questionnaire and other pain measures in the assessment of osteoarthritis pain: a pooled analysis of three celecoxib pivotal studies. Am J Ther 2003;10:12-20
   PubMedGoogle Scholar
• Simon LS, Grierson LM, Naseer Z, et al. 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;143:238-45
   PubMed Web of Science ®Google Scholar
• 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;31:2002-12
   PubMed Web of Science ®Google Scholar
• Farrar JT, Young JP Jr, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149-58
   PubMed Web of Science ®Google Scholar
• Pham T, van der Heijde D, Altman RD, et al. OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage 2004;12:389-99
   PubMed Web of Science ®Google Scholar
• Trijau S, Avouac J, Escalas C, et al. Influence of flare design on symptomatic efficacy of non-steroidal anti-inflammatory drugs in osteoarthritis: a meta-analysis of randomized placebo-controlled trials. Osteoarthritis Cartilage 2010;18:1012-18
   PubMed Web of Science ®Google Scholar
• Bjordal JM, Klovning A, Ljunggren AE, et al. Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: a meta-analysis of randomised placebo-controlled trials. Eur J Pain 2007;11:125-38
   PubMed Web of Science ®Google Scholar
• Hróbjartsson A, Gøtzsche P. Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment. J Intern Med 2004;256:91-100
   PubMed Web of Science ®Google Scholar
• Zhang W, Robertson J, Jones AC, et al. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis 2008;67:1716-23
   PubMed Web of Science ®Google Scholar
• Rother M, Vester J, Bolten W, et al. Meta-analysis of four 12-week phase III clinical trials investigating the effect of TDT 064, a transdermal gel, in osteoarthritis of the knee. Arthritis Rheum 2012;64:Abstract no. 257
   Google Scholar
• FLEXISEQ® Patient Leaflet, 2011. Available at: http://www.flexiseq.com/patient-leaflet [Last accessed 19 August 2013]
   Google Scholar
• Study report CL-033-III-04: a double-blind, placebo-controlled evaluation of the safety and efficacy of three doses of topically applied ketoprofen Transfersome gel in comparison to oral naproxen for the treatment of the signs and symptoms of osteoarthritis of the knee. Germany: IDEA AG, 4 August 2008
   Google Scholar
• Study report CL-033-III-05: a double-blind, long-term evaluation of the safety of topically applied ketoprofen Transfersome gel in comparison to oral naproxen for the treatment of the signs and symptoms of osteoarthritis of the knee. Germany: IDEA AG, 15 December 2008
   Google Scholar