Subscribe to RSS
DOI: 10.1055/s-2006-921338
© Georg Thieme Verlag Stuttgart · New York
Systemische Applikation von Rhenium-186 Hydroxyethylidendiphosphonat (186Re HEDP) als Therapieoption bei chronischen Arthritiden und Arthropathien
Systemic Application of Rhenium-186 Hydroxyethylidenediphosphonate (186Re HEDP) as an Option for the Treatment of Chronic Arthritis and ArthropathyPublication History
Publication Date:
02 March 2006 (online)

Zusammenfassung
Während chronische Arthritiden häufig und mit verschiedenen Systemerkrankungen vergesellschaftet sind, handelt es sich bei der hämophilen Arthropathie um eine der häufigsten klinischen Manifestationen einer Hämophilie, vor allem vom Typ A. Alle diese polyartikulären Erkrankungen führen zu einer progressiven Schmerzsymptomatik und einem zunehmenden Maß an Immobilität. Die Therapie basiert in der Regel auf konservativen Maßnahmen wie nicht-steroidalen anti-phlogistischen Medikamenten, selektiven Behandlungsstrategien wie intraartikulären Injektionen mit z. B. radioaktiven Substanzen (Radiosynoviorthese) sowie chirurgischen Interventionen. In einigen Fällen führen die genannten Maßnahmen jedoch nicht zu einem ausreichenden therapeutischen Erfolg bzw. können aufgrund ihres Nebenwirkungsspektrums nicht angewendet werden. Die systemische Applikation von radioaktiven Substanzen wie z. B. 186Re HEDP ist ein seit Jahren mit Erfolg durchgeführtes Verfahren zur Schmerztherapie von ossären Metastasen, wohingegen wenige Daten zur systemischen Therapie mit 186Re HEDP bei gutartigen polyartikulären Erkrankungen existieren. In einer prospektiven Studie an Patienten mit chronischer Arthritis konnte durch eine einmalige systemische Therapie mit 186Re HEDP ein Rückgang der Krankheits-Aktivität bei sechs von acht sowie eine Abnahme der Anzahl schmerzhafter bzw. geschwollener Gelenke bei fünf von acht eingeschlossenen Patienten gezeigt werden. In einer ebenfalls prospektiven Studie mit 12 Patienten mit hämophiler Arthropathie zeigte sich ein Erfolg der systemischen Schmerztherapie mit 186Re HEDP bei 19 von 36 (52,7 %) am stärksten betroffenen Gelenken sowie eine Reduktion der generellen Schmerzsymptomatik. Weitere randomisierte Studien an größeren Studienpopulationen sind jedoch notwendig, um diese ersten viel versprechenden Ergebnisse zu bestätigen.
Abstract
Chronic arthritis is very common and is associated with a variety of systemic diseases whereas hemophilic arthropathy is one of the most common clinical manifestations of hemophilia, mainly of hemophilia type A. All of these polyarticular diseases are associated with progressive pain and increasing lack of mobility. Therapy is based on conservative treatment such as medication with non-steroidal anti-inflammatory drugs, selective therapy strategies such as intraarticular injections of e. g. radioactive substances (radiosynoviorthesis) or surgical interventions. However, in some cases, the disease does not respond to one of these treatment options or cannot be continued due to important side-effects. Systemic application of radioisotopes like 186Re HEDP has been successfully administered for pain palliation of osseous metastases. Today, only few data exist for systemic therapy with 186Re HEDP in patients suffering from benign polyarticular disease. In a prospective study with patients suffering from chronic arthritis a single systemic application of 186Re HEDP led to a reduction of disease activity in six of eight and to a reduction of the number of painful or swollen joints in five of eight included patients. In a further prospective study with 12 patients with hemophilic arthropathy, 19 of 36 (52.7 %) most painful joints could be successfully treated with one systemic 186Re HEDP therapy. Furthermore, a reduction of global pain could be observed in those patients. However, further randomized studies with larger study populations are necessary in order to confirm this promising results.
Schlüsselwörter
chronische Arthritis - hämophile Arthropathie - Rhenium-186-HEDP - Schmerztherapie
Key words
chronic arthritis - hemophilic arthropathy - Rhenium-186 HEDP - pain therapy
Literatur
- 1 Fries J F, Hochberg M C, Medsger T A, Hunder C G, Bombardier C. Criteria for rheumatic disease. Arthritis Rheum. 1994; 4 454-462
- 2 Stewart Q J, Silamn A J. Review of UK data on rheumatic diseases. IV. Gout. Br J Rheumatol. 1990; 29 485-488
- 3 Strunk J, Lange U, Müller-Ladner U. Rheumatoide Arthritis. Dtsch Med Wochenschr. 2005; 130 1761-1768
- 4 Elder J T, Nair R P, Henseler T, Jenisch S, Stuart P, Chia N, Christophers E, Voorhees J J. The genetics of psoriasis 2001; the odyssey continues. Arch Dermatol. 2001; 137 1447-1454
- 5 Rahman P, Elder J T. Gentic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis. 2005; 64 37-39
- 6 Helliwell P S, Wright V. PsA: clinical features. In: Klippel JH, Dieppe PA (eds). Rheumatology. Mosby, London 1998; 6.21.1-6.21.8
- 7 Helliwell P S, Taylor W J. Classification and diagnostic criteria for psoriatic arthritis. Ann Rheum Dis. 2005; 64 3-8
- 8 Veale D J. The epidemiology of psoriatic arthritis: fact or fiction?. J Rheumatol. 2000; 27 1105-1106
- 9 Hochberg M C, Perlmutter D L, Medsger T A, Steen V, Weisman M H, White B, Wigley F M. Prevalence of self-reported physician-diagnosed systemic lupus erythematosus in the USA. Lupus. 1995; 6 454-456
- 10 Manzi S. Epidemiology of systemic lupus erythematosus. Am J Manag Care. 2001; 7 S 474-S 479
- 11 Boumpas D T, Fessler B J, Austin H A, Balow J E, Klippel J H, Lockshin M D. Systemic lupus erythematosus. Ann Int Med. 1995; 123 42-53
- 12 Cronin M E. Muskuloskeletal manifestation of systemic lupus erythematosus. Rheum Dis Clin North Am. 1988; 14 99-116
- 13 Brand C A, Rowley M J, Tait B D, Muirden K D, Whittingham S F. Coexistent rheumatoid arthritis and systemic lupus erythematosus: clinical, serological, and phenotypic features. Ann Rheum Dis. 1992; 51 173-176
- 14 Hilgartner M W. Current treatment of hemophilic arthropathy. Curr Opin Pediatr. 2002; 14 46-49
- 15 Luck J V, Silva M, Rodriguez-Merchan E C, Ghalambor N, Zahiri C A, Finn R S. Hemophilic arthropathy. J Am Acad Orthop Surg. 2004; 12 234-245
- 16 Chang T J, Mohamed S, Hambleton J. Hemophilic arthropathy: considerations in management. J Am Pdiatr Med Assoc. 2001; 91 406-414
- 17 Müller S, Kurth A A, Hovy L. Konservative Behandlungsmaßnahmen der hämophilen Arthropathie. Orthopäde. 1999; 28 347-355
- 18 Rodriguez-Merchan E C. Pathogenesis, early diagnosis, and prophylaxis for chronic hemophilic synovitis. Clin Orthop. 1997; 343 6-11
- 19 McCarthy D J, Manzi S, Medsger T A, Ramsey-Goldman R, LaPorte R E, Kwoh C K. Incidence of systemic lupus erythomatosus. Arthritis Rheum. 1995; 38 1260-1270
- 20 Olivera S A, Felson D T, Reed J I, Cirillo P A, Walker A M. Incidence of symptomatic hand, hip and knee osteoarthritis among patients in a health maintenance organization. Arthritis Rheum. 1995; 38 1134-1141
- 21 Symmons D PM, Barett E M, Chakravorty K, Scott D GI, Silman A J. The incidence of rheumatic arthritis in Norfolk, England. Arthritis Rheum. 1992; 35 (Suppl) 126
- 22 Wallny T, Hess L, Seuser A, Zander D, Brackmann H H, Kraft C N. Pain status of patients with severe haemophilic arthropathy. Haemophilia. 2001; 7 453-458
- 23 Odeh M. Short analytical review: new insight into the pathogenesis and treatment of rheumatoid arthritis. Clin Immunol Immunopathol. 1997; 83 103-116
- 24 Wagner U, Kaltenhauser S, Sauer H, Arnold S, Seidel W, Hantzschel H, Kalden J R, Wassmuth R. HLA markers and prediction of clinical course and outcome in rheumatoid arthritis. Arthritis Rheum. 1997; 40 341-351
- 25 Alarcon G S, Tracy I C, Blackburn W D. Methotrexate in rheumatoid arthritis. Arthritis Rheum. 1989; 32 671-676
- 26 Brodgen R N, Wiseman L R. Aceclofenac: a review its pharmacodynamic properties and therapeutic potential in the treatment of rheumatic disorders and in pain management. Drugs. 1996; 52 113-124
- 27 Connor J, Nalebuff E A. Current recommendations for surgery of the rheumatoid hand and wrist. Curr Opin Rheumatol. 1995; 7 120-124
- 28 O'Duffy E K, Ell P J. The practice of medical and surgical synovectomy: a UK survey. Nucl Med Commun. 1999; 20 21-24
- 29 Siegel M E, Siegel H J, Luck J V. Radiosynovectomy's clinical applications and cost effectiveness: a review. Semin Nucl Med. 1997; 27 364-371
- 30 Taylor W J, Corkill M M, Rajapaske C N. A retrospective review of yttrium-90 synovectomy in the treatment of knee arthritis. Br J Rheumatol. 1997; 36 1100-1105
- 31 Dunn A L, Busch M T, Wyly J B, Abshire T C. Radionuclide synovectomy for hemophilic arthropathy: A comprehensive review of safety and efficacy and recommendation for a standardized treatment protocol. Thromb Haemost. 2002; 87 383-393
- 32 Rodriguez-Merchan E C. Radionuclide synovectomy (Radiosynoviorthesis) in hemophilia: A very efficient and single procedure. Semin Thromb Hemost. 2003; 29 97-100
- 33 Rodriguez-Merchan E C, Wiedel J D, Wallny T, Caviglia H, Hvid I, Berntorp E, Rivard G E, Goddard N N, Querol F. Elective orthopedic surgery for hemophilia patients with inhibitors: New opportunities. Semin Hematol. 2004; 41 (Suppl 1) 109-116
- 34 Wallny T, Brackmann H H, Semper H, Schumpe G, Effenberger W, Hess L, Seuser A. Intra-articular hyaluronic acid in the treatment of haemophilic arthropathy of the knee. A clinical, radiological and sonographical assessment. Haemophilia. 2000; 6 566-570
- 35 De Klerk J MH, Zonnenberg B A, het Schip A D van, Dijk A van, Han S H, Quirijnen J M, Blijham G H, Rijk P P van. Dose escalation study of rhenium-186-HEDP in patients with metastatic prostate cancer. Eur J Nucl Med. 1994; 21 1114-1120
- 36 de Klerk J M, het Schip A D van, Zonnenberg B A, Dijk A van, Quirijnen J M, Blijham G H, Rijk P P van. Phase 1 study of rhenium-186-HEDP in patients with bone metastases originating from breast cancer. J Nucl Med. 1996; 37 244-249
- 37 Maxon H R, Deutsch E A, Thomas S R, Libson K, Lukes S J, Williams C C, Ali S. Rhenium-186(Sn) HEDP for treatment of multiple metastatic foci in bone: human distribution and dosimetric studies. Radiology. 1988; 166 501-507
- 38 Maxon H R, Schroder L E, Thomas S R, Hertzberg V S, Deutsch E A, Scher H I, Samaratunga R C, Libson K F, Williams C C, Moulton J S. Rhenium-186(Sn) HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer. Radiology. 1990; 176 155-159
- 39 Palmedo H, Guhlke S, Bender H, Sartor J, Schoeneich G, Risse J, Grunwald F, Knapp F F, Biersack H J. Dose escalation study with rhenium-188HEDP in prostate cancer patients with osseous metastases. Eur J Nucl Med. 2000; 27 123-130
- 40 Palmedo H, Manka-Waluch A, Albers P, Schmidt-Wolf I G, Reinhardt M, Ezziddin S, Joe A, Roedel R, Fimmers R, Knapp F F, Guhlke S, Biersack H J. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: randomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. J Clin Oncol. 2003; 21 2869-2875
- 41 Quirijnen J M, Han S H, Zonnenberg B A, de Klerk J M, het Schip A D van, Dijk A van, ten Kroode H F, Blijham G H, Rijk P P van. Efficacy of rhenium-186-HEDP etidronate in prostate cancer patients with metastatic bone pain. J Nucl Med. 1996; 37 1511-1515
- 42 Schoeneich G, Palmedo H, Dierke-Dzierzon C, Muler S C, Biersack H J. Rhenium-186 HEDP: palliative radionuclide therapy of painful bone metastases. Preliminary results. Scand J Urol Nephrol. 1997; 31 445-448
- 43 Palmedo H, Rockstroh J K, Bangard M, Schliefer K, Risse J, Menzel C, Biersack H J. Painful multifocal arthritis: therapy with rhenium 186 hydroxyethylidenediphosphonate (186Re HEDP) after failed treatment with medication - initial results of a prospective study. Radiology. 2001; 221 256-260
- 44 Bucerius J, Wallny T, Brackmann H H, Joe A Y, Roedel R, Biersack H J, Palmedo H. Rhenium-186 Hydroxyethylidenediphosphonate (186Re HEDP) for the treatment of hemophilic arthropathies. First results. J Nucl Med. 2005; 46 (Suppl) 184 P
- 45 Wallny T A, Heß L, Brackmann H H, Seuser A, Palmedo H, Kraft C. Rhenium-186 Hydroxyethylidenediphosphonate (186Re HEDP) - A novel treatment for haemophilic
arthropathies?. In: Scharrer I, Schramm W (eds). 32th Hemophilia Symposium Hamburg 2001. Springer-Verlag,
Heidelberg 2002; 87-91
- 46 Arnett F C, Edworthy S M, Bloch D A, McShane D J, Fries J F, Cooper N S, Healey L A, Kaplan S R, Liang M H, Luthra H S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31 315-324
- 47 Felson D T, Anderson J J, Boers M, Bombadier C, Chernoff M, Fried B, Furst D, Goldsmith C, Kieszak S, Lightfood R. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials: the Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum. 1993; 36 729-740
- 48 Price D D, McGrath P A, Rafii A, Buckingham B. The validation of visual analogue scale as ratio scale measures for chronic and experimental pain. Pain. 1983; 17 45-56
- 49 Sriwatanakul K, Kelvie W, Lasagna L, Calimlim J F, Weis O F, Mehta G. Studies with different types of visual analog scale for measurement of pain. Clin Pharmacol Ther. 1983; 34 234-239
- 50 Gratz S, Gobel D, Behr T M, Herrmann A, Becker W. Correlation between radiation dose, synovial thickness, and efficacy of radiosynoviorthesis. J Rheumatol. 1999; 26 1242-1249
Dr. med. Jan Bucerius
Klinik und Poliklinik für Nuklearmedizin · Universitätsklinikum Bonn
Sigmund-Freud-Straße 25
53105 Bonn
Phone: ++49/2 28/2 87 51 81
Fax: ++49/2 28/2 87 10 16
Email: jan.bucerius@ukb.uni-bonn.de