Use of gold compounds in rheumatic diseases
- Alice Klinkhoff, MD
Alice Klinkhoff, MD
- Clinical Associate Professor
- University of British Columbia
- Section Editor
- Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
- Section Editor — Rheumatoid Arthritis
- Emeritus Professor of Rheumatology, Imperial College London
- Visiting Professor, Oxford University
Gold compounds have been employed for the treatment of rheumatoid arthritis (RA) since Forestier pioneered their use for this purpose in 1929 . Subsequent randomized trials confirmed the effectiveness of gold in RA (see 'Efficacy of parenteral gold in RA' below). Gold has also been used in psoriatic arthritis and juvenile idiopathic arthritis. However, since the 1980s the use of gold has declined due to multiple advantages of other medications, particularly methotrexate (MTX), when compared with gold; the benefits of these newer medications include convenience, safety, efficacy, and cost.
The pharmacokinetics and use of gold in the treatment of RA are reviewed here. The toxicities of gold therapy, the initial treatment of RA with disease-modifying antirheumatic drugs (DMARDs), and the treatment of RA resistant to initial DMARD therapy are discussed in detail separately. (See "Major side effects of gold therapy" and "Initial treatment of rheumatoid arthritis in adults" and "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy", section on 'Resistant to standard therapies' and "Treatment of rheumatoid arthritis in adults resistant to initial nonbiologic DMARD therapy".)
Therapeutic gold compounds — Two therapeutic products containing gold are available:
●Gold sodium thiomalate (GST), which contains almost 50 percent gold in a water-based solution and is administered by intramuscular (IM) injection every one to four weeks.
●Auranofin, which is a gold triethylphosphine compound taken orally each day.
Subscribers log in hereLiterature review current through: Jul 2017. | This topic last updated: Sep 15, 2016.References
- Forestier, J. Rheumatoid arthritis and its treatment by gold salts. J Lab Clin Med 1935; 20:827.
- Noriega JLR, Harth M. Pharmacology of gold compounds in rheumatoid arthritis: A review. Can J Clin Pharmacol 1997; 4:127.
- De Wall SL, Painter C, Stone JD, et al. Noble metals strip peptides from class II MHC proteins. Nat Chem Biol 2006; 2:197.
- Stuhlmeier KM. The anti-rheumatic gold salt aurothiomalate suppresses interleukin-1beta-induced hyaluronan accumulation by blocking HAS1 transcription and by acting as a COX-2 transcriptional repressor. J Biol Chem 2007; 282:2250.
- Tuure L, Hämäläinen M, Moilanen T, Moilanen E. Aurothiomalate inhibits the expression of mPGES-1 in primary human chondrocytes. Scand J Rheumatol 2015; 44:74.
- Tsai CY, Shiau AL, Chen SY, et al. Amelioration of collagen-induced arthritis in rats by nanogold. Arthritis Rheum 2007; 56:544.
- Nieminen R, Korhonen R, Moilanen T, et al. Aurothiomalate inhibits cyclooxygenase 2, matrix metalloproteinase 3, and interleukin-6 expression in chondrocytes by increasing MAPK phosphatase 1 expression and decreasing p38 phosphorylation: MAPK phosphatase 1 as a novel target for antirheumatic drugs. Arthritis Rheum 2010; 62:1650.
- Jones G, Brooks PM. Injectable gold compounds: an overview. Br J Rheumatol 1996; 35:1154.
- Gordon, DA. Gold compounds. In. Textbook of Rheumatology, 5th ed, Kelley, WN, Harris, ED, Ruddy, S, Sledge, CB (Eds). WB Saunders, Philadelphia, 1997, pp. 759-769.
- O'Dell JR, Petersen K, Leff R, et al. Etanercept in combination with sulfasalazine, hydroxychloroquine, or gold in the treatment of rheumatoid arthritis. J Rheumatol 2006; 33:213.
- Ohtsubo H, Matsuda T. [Effective combination therapy of TNF antagonists with DMARDs]. Nihon Rinsho 2007; 65:1287.
- Cheung JM, Scarsbrook D, Klinkhoff AV. Characterization of patients with arthritis referred for gold therapy in the era of biologics. J Rheumatol 2012; 39:716.
- Speerstra F, van Riel PL, Reekers P, et al. The influence of HLA phenotypes on the response to parenteral gold in rheumatoid arthritis. Tissue Antigens 1986; 28:1.
- Klinkhoff AV, Teufel A. How low can you go? Use of very low dosage of gold in patients with mucocutaneous reactions. J Rheumatol 1995; 22:1657.
- Sagransky DM, Greenwald RA. Efficacy and toxicity of retreatment with gold salts: a retrospective review of 25 cases. J Rheumatol 1980; 7:474.
- Klinkhoff AV, Teufel A. The second course of gold. J Rheumatol 1995; 22:1655.
- Lehman AJ, Esdaile JM, Klinkhoff AV, et al. A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study. Arthritis Rheum 2005; 52:1360.
- Gottlieb NL, Brown HE Jr. Acute myocardial infarction following gold sodium thiomalate induced vasomotor (nitritoid) reaction. Arthritis Rheum 1977; 20:1026.
- Arthur AB, Klinkhoff A, Teufel A. Nitritoid reactions: case reports, review, and recommendations for management. J Rheumatol 2001; 28:2209.
- Ching DW, McClintock AD. Nitritoid reaction in a patient on ACE inhibitor and Myocrisin treatments. Aust N Z J Med 1997; 27:343.
- Almarzouqi M, Scarsbrook D, Klinkhoff A. Gold therapy in women planning pregnancy: outcomes in one center. J Rheumatol 2007; 34:1827.
- Tarp U, Graudal H. A followup study of children exposed to gold compounds in utero. Arthritis Rheum 1985; 28:235.
- Miyamoto T, Miyaji S, Horiuchi Y, et al. [Gold therapy in bronchial asthma with special emphasis upon blood level of gold and its teratogenicity (author's transl)]. Nihon Naika Gakkai Zasshi 1974; 63:1190.
- Cohen DL, Orzel J, Taylor A. Infants of mothers receiving gold therapy. Arthritis Rheum 1981; 24:104.
- American Academy of Pediatrics Committee on Drugs: The transfer of drugs and other chemicals into human milk. Pediatrics 1994; 93:137.
- Reddy JM, Joyce C, Zaneveld LJD. Role of hyaluronidase in fertilization: The antifertility activity of myocrisin, a non-toxic hyaluronidase inhibitor. J Androl 1979; 1:28.
- Srinivasan R, Miller BL, Paulus HE. Long-term chrysotherapy in rheumatoid arthritis. Arthritis Rheum 1979; 22:105.
- Hartfall SJ, Harland HG, Goldie W. Gold treatment of arthritis. A review of 900 cases. Lancet 1937; 230:838.
- RESEARCH SUB-COMMITTEE OF THE EMPIRE RHEUMATISM COUNCIL. Gold Therapy in Rheumatoid Arthritis: Final Report of a Multicentre Controlled Trial. Ann Rheum Dis 1961; 20:315.
- A controlled trial of gold salt therapy in rheumatoid arthritis. Arthritis Rheum 1973; 16:353.
- Sigler JW, Bluhm GB, Duncan H, et al. Gold salts in the treatment of rheumatoid arthritis. A double-blind study. Ann Intern Med 1974; 80:21.
- Munro R, Hampson R, McEntegart A, et al. Improved functional outcome in patients with early rheumatoid arthritis treated with intramuscular gold: results of a five year prospective study. Ann Rheum Dis 1998; 57:88.
- Hartfall SJ, Garland HG, Goldie W. Gold treatment of arthritis. A review of 900 cases. Lancet 1937; 230:784.
- Clark P, Tugwell P, Bennet K, et al. Injectable gold for rheumatoid arthritis. Cochrane Database Syst Rev 2000; :CD000520.
- GOLD therapy in rheumatoid arthritis. Report of a multicentre control trial. Ann Rheum Dis 1960; 19:95.
- Ward JR, Williams HJ, Egger MJ, et al. Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 1983; 26:1303.
- Buckland-Wright JC, Clarke GS, Chikanza IC, Grahame R. Quantitative microfocal radiography detects changes in erosion area in patients with early rheumatoid arthritis treated with myocrisine. J Rheumatol 1993; 20:243.
- Cats A. A multicentre controlled trial of the effects of different dosage of gold therapy, followed by a maintenance dosage. Agents Actions 1976; 6:355.
- Furst DE, Levine S, Srinivasan R, et al. A double-blind trial of high versus conventional dosages of gold salts for rheumatoid arthritis. Arthritis Rheum 1977; 20:1473.
- Sharp JT, Lidsky MD, Duffy J, et al. Comparison of two dosage schedules of gold salts in the treatment of rheumatoid arthritis. Relationship of serum gold levels to therapeutic response. Arthritis Rheum 1977; 20:1179.
- McKenzie JM. Report on a double-blind trial comparing small and large doses of gold in the treatment of rheumatoid disease. Rheumatol Rehabil 1981; 20:198.
- Pullar T, Hunter JA, Capell HA. Sulphasalazine in rheumatoid arthritis: a double blind comparison of sulphasalazine with placebo and sodium aurothiomalate. Br Med J (Clin Res Ed) 1983; 287:1102.
- Felson DT, Anderson JJ, Meenan RF. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses. Arthritis Rheum 1990; 33:1449.
- Rau R, Herborn G, Menninger H, Blechschmidt J. Comparison of intramuscular methotrexate and gold sodium thiomalate in the treatment of early erosive rheumatoid arthritis: 12 month data of a double-blind parallel study of 174 patients. Br J Rheumatol 1997; 36:345.
- Rau R, Herborn G, Menninger H, Sangha O. Progression in early erosive rheumatoid arthritis: 12 month results from a randomized controlled trial comparing methotrexate and gold sodium thiomalate. Br J Rheumatol 1998; 37:1220.
- Rau R, Herborn G, Menninger H, Sangha O. Radiographic outcome after three years of patients with early erosive rheumatoid arthritis treated with intramuscular methotrexate or parenteral gold. Extension of a one-year double-blind study in 174 patients. Rheumatology (Oxford) 2002; 41:196.
- Scott DL, Dawes PT, Tunn E, et al. Combination therapy with gold and hydroxychloroquine in rheumatoid arthritis: a prospective, randomized, placebo-controlled study. Br J Rheumatol 1989; 28:128.
- Sander O, Herborn G, Bock E, Rau R. Prospective six year follow up of patients withdrawn from a randomised study comparing parenteral gold salt and methotrexate. Ann Rheum Dis 1999; 58:281.
- Elkayam O, Yaron M, Zhukovsky G, et al. Toxicity profile of dual methotrexate combinations with gold, hydroxychloroquine, sulphasalazine and minocycline in rheumatoid arthritis patients. Rheumatol Int 1997; 17:49.
- Bensen W, Tugwell P, Roberts RM, et al. Combination therapy of cyclosporine with methotrexate and gold in rheumatoid arthritis (2 pilot studies). J Rheumatol 1994; 21:2034.
- Heath MJ. Measurement of 'free' gold in patients receiving disodium aurothiomalate and the association of high free to total gold levels with toxicity. Ann Rheum Dis 1988; 47:18.
- Heytman M, Ahern MJ, Smith MD, Roberts-Thomson PJ. The longterm effect of pulsed corticosteroids on the efficacy and toxicity of chrysotherapy in rheumatoid arthritis. J Rheumatol 1994; 21:435.
- Situnayake RD, Grindulis KA, McConkey B. Long-term treatment of rheumatoid arthritis with sulphasalazine, gold, or penicillamine: a comparison using life-table methods. Ann Rheum Dis 1987; 46:177.
- Wolfe F, Hawley DJ, Cathey MA. Measurement of gold treatment effect in clinical practice: evidence for effectiveness of intramuscular gold therapy. J Rheumatol 1993; 20:797.
- Lehtinen K, Isomäki H. Intramuscular gold therapy is associated with long survival in patients with rheumatoid arthritis. J Rheumatol 1991; 18:524.
- Capell HA, Lewis D, Carey J. A three year follow up of patients allocated to placebo, or oral or injectable gold therapy for rheumatoid arthritis. Ann Rheum Dis 1986; 45:705.
- Davis P, Menard H, Thompson J, et al. One-year comparative study of gold sodium thiomalate and auranofin in the treatment of rheumatoid arthritis. J Rheumatol 1985; 12:60.
- Borg G, Allander E, Lund B, et al. Auranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study. J Rheumatol 1988; 15:1747.
- Prete PE, Zane J, Krailo M, Bulanowski M. Randomized trial of switching rheumatoid arthritis patients in remission with injectable gold to auranofin. Clin Rheumatol 1994; 13:60.
- Lacaille D, Stein HB, Raboud J, Klinkhoff AV. Longterm therapy of psoriatic arthritis: intramuscular gold or methotrexate? J Rheumatol 2000; 27:1922.
- Pandya AG, Dyke C. Treatment of pemphigus with gold. Arch Dermatol 1998; 134:1104.
- Iranzo P, Alsina MM, Martínez-De Pablo I, et al. Gold: an old drug still working in refractory pemphigus. J Eur Acad Dermatol Venereol 2007; 21:902.
- Therapeutic gold compounds
- Mechanism of action
- Drug interactions
- USE OF GOLD IN RA
- Dose schedules
- - Dosing of parenteral gold
- - Dosing of oral gold
- Contraindications and precautions
- Pregnancy and lactation
- Monitoring for toxicity
- - Monitoring parenteral gold
- - Monitoring oral gold
- Duration of therapy
- EFFICACY OF GOLD THERAPY
- Efficacy of parenteral gold in RA
- - Gold versus placebo
- - Gold versus other DMARDs
- - Gold combined with other drugs
- - Long-term effectiveness
- Efficacy of oral gold
- Determinants of efficacy
- USE IN DISORDERS OTHER THAN RA
- SUMMARY AND RECOMMENDATIONS