Original Article

You have full text access to this OnlineOpen article

A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis

  1. Gary S. Hoffman1,*,
  2. Maria C. Cid2,
  3. David B. Hellmann3,
  4. Loic Guillevin4,
  5. John H. Stone3,
  6. John Schousboe5,
  7. Pascal Cohen4,
  8. Leonard H. Calabrese1,
  9. Howard Dickler6,
  10. Peter A. Merkel7,
  11. Paul Fortin8,
  12. John A. Flynn3,
  13. Geri A. Locker1,
  14. Kirk A. Easley1,
  15. Eric Schned5,
  16. Gene G. Hunder9,
  17. Michael C. Sneller6,
  18. Carol Tuggle1,
  19. Howard Swanson10,
  20. J. Hernández-Rodríguez2,
  21. Alfons Lopez-Soto2,
  22. Debora Bork1,
  23. Diane B. Hoffman1,
  24. Kenneth Kalunian11,
  25. David Klashman11,
  26. William S. Wilke1,
  27. Raymond J. Scheetz1,
  28. Brian F. Mandell1,
  29. Barri J. Fessler1,
  30. Gregory Kosmorsky1,
  31. Richard Prayson1,
  32. Raashid A. Luqmani12,
  33. George Nuki12,
  34. Euan McRorie12,
  35. Yvonne Sherrer13,
  36. Shawn Baca14,
  37. Bridgit Walsh15,
  38. Diane Ferland7,
  39. Martin Soubrier4,
  40. Hyon K. Choi7,
  41. Wolfgang Gross16,
  42. Allen M. Segal1,
  43. Charles Ludivico17,
  44. Xavier Puechal4,
  45. International Network for the Study of Systematic Vasculitides (INSSYS)

Article first published online: 8 MAY 2002

DOI: 10.1002/art.10262

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 46, Issue 5, pages 1309–1318, May 2002

Additional Information

How to Cite

Hoffman, G. S., Cid, M. C., Hellmann, D. B., Guillevin, L., Stone, J. H., Schousboe, J., Cohen, P., Calabrese, L. H., Dickler, H., Merkel, P. A., Fortin, P., Flynn, J. A., Locker, G. A., Easley, K. A., Schned, E., Hunder, G. G., Sneller, M. C., Tuggle, C., Swanson, H., Hernández-Rodríguez, J., Lopez-Soto, A., Bork, D., Hoffman, D. B., Kalunian, K., Klashman, D., Wilke, W. S., Scheetz, R. J., Mandell, B. F., Fessler, B. J., Kosmorsky, G., Prayson, R., Luqmani, R. A., Nuki, G., McRorie, E., Sherrer, Y., Baca, S., Walsh, B., Ferland, D., Soubrier, M., Choi, H. K., Gross, W., Segal, A. M., Ludivico, C., Puechal, X. and International Network for the Study of Systematic Vasculitides (INSSYS) (2002), A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis & Rheumatism, 46: 1309–1318. doi: 10.1002/art.10262

Author Information

  1. 1

    Cleveland Clinic Foundation, Cleveland, Ohio

  2. 2

    Hospital Clinic í Provincial, Barcelona, Spain

  3. 3

    Johns Hopkins University School of Medicine, Baltimore, Maryland

  4. 4

    Universite Paris XIII, Paris, France

  5. 5

    Park Nicollet Medical Foundation, St. Louis Park, Minnesota

  6. 6

    NIH, Bethesda, Maryland

  7. 7

    Massachusetts General Hospital, Boston

  8. 8

    Montreal General Hospital/McGill University, Montreal, Quebec, Canada

  9. 9

    Mayo Clinic, Rochester, Minnesota

  10. 10

    Marshfield Clinic, Marshfield, Wisconsin

  11. 11

    University of California, Los Angeles

  12. 12

    Western General Hospital, Edinburgh, Scotland

  13. 13

    Center for Rheumatology, Immunology & Arthritis, Fort Lauderdale, Florida, and Rheumatology Association of South Florida, Delray Beach

  14. 14

    Center for Rheumatology, Immunology & Arthritis, Fort Lauderdale, Florida

  15. 15

    University of Arizona, Tucson

  16. 16

    Medizinische Universitat zu Lubeck, Lubeck, Germany

  17. 17

    Bethlehem, Pennsylvania

*Harold C. Schott Chair of Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation A50, 9500 Euclid Avenue, Cleveland, OH 44915

Publication History

  1. Issue published online: 8 MAY 2002
  2. Article first published online: 8 MAY 2002
  3. Manuscript Accepted: 11 JAN 2002
  4. Manuscript Received: 25 SEP 2001

Funded by

  • Food and Drug Administration and the Office of Orphan Products Development. Grant Number: FD-R 001040
  • George B. Storer Foundation
  • Ayhan Sahenk Foundation
  • Fondo de Investigación Sanitaria. Grant Number: FIS 98/0443

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (105K)

REFERENCES

  • 1
    Salvarani C, Gabriel SE, O'Fallon WM, Hunder GG. The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern. Ann Intern Med 1995; 123: 192–4.
  • 2
    Matteson EL, Gold KN, Block DA, Hunder GG. Long-term survival of patients with giant cell arteritis in the American College of Rheumatology giant cell arteritis classification criteria cohort. Am J Med 1996; 100: 193–6.
  • 3
    Robb-Nicholson C, Chang RW, Anderson S, Roberts WN, Longtine J, Corson J, et al. Diagnostic value of the history and examination in giant cell arteritis: a clinical pathological study of 81 temporal artery biopsies. J Rheumatol 1988; 15: 1793–6.
  • 4
    Nesher G, Sonnenblick M, Friedlander Y. Analysis of steroid related complications and mortality in temporal arteritis: a 15-year survey of 43 patients. J Rheumatol 1994; 21: 1283–6.
  • 5
    Nesher G, Rubinow A, Sonnenblick M. Efficacy and adverse effects of different corticosteroid dose regimens in temporal arteritis: a retrospective study. Clin Exp Rheumatol 1997; 15: 303–6.
  • 6
    Delecoeuillerie G, Joly P, Cohen de Lara A, Paolaggi JB. Polymyalgia rheumatica and temporal arteritis: a retrospective analysis of prognostic features and different corticosteroid regimens (11 year survey of 210 patients). Ann Rheum Dis 1988; 47: 733–9.
  • 7
    Graham E, Holland A, Avery A, Russell RW. Prognosis in giant-cell arteritis. BMJ (Clin Res Ed) 1981; 282: 269–71.
  • 8
    Hachulla E, Boivin V, Pasturel-Michon U, Fauchais AL, Bouroz-Joly J, Perez-Cousin M, et al. Prognosis factors and long-term evolution in a cohort of 133 patients with giant cell arteritis. Clin Exp Rheumatol 2001; 19: 171–6.
  • 9
    Kyle V, Hazleman BL. Treatment of polymyalgia rheumatica and giant cell arteritis. I. Steroid regimens in the first two months. Ann Rheum Dis 1989; 48: 658–61.
  • 10
    Kyle V, Hazleman BL. Treatment of polymyalgia rheumatica and giant cell arteritis. II. Relation between steroid dose and steroid associated side effects. Ann Rheum Dis 1989; 48: 662–6.
  • 11
    Myklebust G, Gran JT. A prospective study of 287 patients with polymyalgia rheumatica and temporal arteritis: clinical and laboratory manifestations at onset of disease and at the time of diagnosis. Br J Rheumatol 1996; 35: 1161–8.
  • 12
    Bengtsson BA, Malmvall BE. The epidemiology of giant cell arteritis including temporal arteritis and polymyalgia rheumatica: incidences of different clinical presentations and eye complications. Arthritis Rheum 1981; 24: 899–904.
    Direct Link:
  • 13
    Gonzalez-Gay MA, Blanco R, Rodriguez-Valverde V, Martinez-Taboada VM, Delgado-Rodriguez M, Figueroa M, et al. Permanent visual loss and cerebrovascular accidents in giant cell arteritis: predictors and response to treatment. Arthritis Rheum 1998; 41: 1497–504.
    Direct Link:
  • 14
    Gordon LK, Levin LA. Visual loss in giant cell arteritis. JAMA 1998; 280: 385–6.
  • 15
    Font C, Cid MC, Coll-Vincent B, Lopez-Soto A, Grau JM. Clinical features in patients with permanent visual loss due to biopsy-proven giant cell arteritis. Br J Rheumatol 1997; 36: 251–4.
  • 16
    Cid MC, Font C, Oristrell J, de la Sierra A, Coll-Vincent B, Lopez-Soto A, et al. Association between strong inflammatory response and low risk of developing visual loss and other cranial ischemic complications in giant cell (temporal) arteritis. Arthritis Rheum 1998; 41: 26–32.
    Direct Link:
  • 17
    Hunder GG. Giant cell (temporal) arteritis. Rheum Dis Clin North Am 1990; 16: 399–409.
  • 18
    Evans JM, O'Fallon WM, Hunder GG. Increased incidence of aortic aneurysm and dissection in giant cell (temporal) arteritis: a population-based study. Ann Intern Med 1995; 122: 502–7.
  • 19
    Greene GM, Lain D, Sherwin RM, Wilson JE, McManus BM. Giant cell arteritis of the legs: clinical isolation of severe disease with gangrene and amputations. Am J Med 1986; 81: 727–33.
  • 20
    Ninet JP, Bachet P, Dumontet CM, Du Colombier PB, Stewart MD, Pasquier JH. Subclavian and axillary involvement in temporal arteritis and polymyalgia rheumatica. Am J Med 1990; 88: 13–20.
  • 21
    Langford CA, Talar-Williams C, Barron KS, Sneller MC. A staged approach to the treatment of Wegener's granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. Arthritis Rheum 1999; 42: 2666–73.
    Direct Link:
  • 22
    Hoffman GS, Leavitt RY, Kerr GS, Fauci AS. The treatment of Wegener's granulomatosis with glucocorticoids and methotrexate. Arthritis Rheum 1992; 35: 1322–9.
  • 23
    Sneller MC, Hoffman GS, Talar-Williams C, Kerr GS, Hallahan CW, Fauci AS. An analysis of forty-two Wegener's granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum 1995; 38: 608–13.
    Direct Link:
  • 24
    De Groot K, Muhler M, Reinhold-Keller E, Paulsen J, Gross WL. Induction of remission in Wegener's granulomatosis with low dose methotrexate. J Rheumatol 1998; 25: 492–5.
  • 25
    Hoffman GS, Leavitt RY, Kerr GS, Rotten M, Sneller MC, Fauci AS. Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate. Arthritis Rheum 1994; 37: 578–82.
    Direct Link:
  • 26
    Genereau T, Lortholary O, Pottier MA, Michon-Pasturel U, Ponge T, de Wazieres B, et al. Temporal artery biopsy: a diagnostic tool for systemic necrotizing vasculitis. Arthritis Rheum 1999; 42: 2674–81.
    Direct Link:
  • 27
    Small P, Brisson ML. Wegener's granulomatosis presenting as temporal arteritis. Arthritis Rheum 1991; 34: 220–3.
    Direct Link:
  • 28
    Nishino H, DeRemee RA, Rubino FA, Parisi JE. Wegener's granulomatosis associated with vasculitis of the temporal artery: report of five cases. Mayo Clin Proc 1993; 68: 115–21.
  • 29
    Sieber SC, Cuello B, Gelfman NA, Garfinkel HB. Pulmonary capillaritis and glomerulonephritis in an antineutrophil cytoplasmic antibody-positive patient with prior granulomatous aortitis. Arch Pathol Lab Med 1990; 114: 1223–6.
  • 30
    Morgan GJ Jr, Harris ED Jr. Non-giant cell arteritis: three cases and a review of the literature. Arthritis Rheum 1978; 21: 362–6.
    Direct Link:
  • 31
    Proctor PR, Lotz BP. Sarcoidosis and giant cell arteritis [letter]. Clin Exp Dermatol 1992; 17: 143–4.
    Direct Link:
  • 32
    Sambrook P, Birmingham J, Kelly P, Kempler S, Nguyen T, Pocock N, et al. Prevention of corticosteroid osteoporosis: a comparison of calcium, calcitriol, and calcitonin. N Engl J Med 1993; 328: 1747–52.
  • 33
    Huston KA, Hunder GG, Lie JT, Kennedy RH, Elveback LR. Temporal arteritis: a 25-year epidemiologic, clinical, and pathologic study. Ann Intern Med 1978; 88: 162–7.
  • 34
    Hunder GG, Sheps SG, Allen GL, Joyce JW. Daily and alternate-day corticosteroid regimens in treatment of giant cell arteritis: comparison in a prospective study. Ann Intern Med 1975; 82: 613–8.
  • 35
    Malmvall BE, Bengtsson BA, Alestig K, Bojs G, Iwarson S. The clinical pictures of giant cell arteritis: temporal arteritis, polymyalgia rheumatica, and fever of unknown origin. Postgrad Med 1980; 67: 141–3, 146–7, 150.
  • 36
    Chmelewski WL, McKnight KM, Agudelo CA, Wise CM. Presenting features and outcomes in patients undergoing temporal artery biopsy: a review of 98 patients. Arch Intern Med 1992; 152: 1690–5.
  • 37
    Gabriel SE, O'Fallon WM, Achkar AA, Lie JT, Hunder GG. The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis. J Rheumatol 1995; 22: 93–6.
  • 38
    Gonzalez-Gay MA, Blanco R, Abraira V, Garcia-Porrua C, Ibanez D, Garcia-Pais MJ, et al. Giant cell arteritis in Lugo, Spain, is associated with low longterm mortality. J Rheumatol 1997; 24: 2171–6.
  • 39
    Jover JA, Hernandez-Garcia C, Morado IC, Vargas E, Banares A, Fernandez-Gutierrez B. Combined treatment of giant-cell arteritis with methotrexate and prednisone: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2001; 134: 106–14.
  • 40
    Weyand CM, Fulbright JW, Hunder GG, Evans JM, Goronzy JJ. Treatment of giant cell arteritis: interleukin-6 as a biologic marker of disease activity. Arthritis Rheum 2000; 43: 1041–8.
    Direct Link:
  • 41
    Proven A, Gabriel S, O'Fallon M, Hunder G. Long-term outcome of corticosteroid therapy in a population-based study of giant cell arteritis (GCA), 1950–1991 [abstract]. Arthritis Rheum 1999; 42 Suppl: S209.
  • 42
    Rojo-Leyva F, Ratliff NB, Cosgrove DM III, Hoffman GS. Study of 52 patients with idiopathic aortitis from a cohort of 1,204 surgical cases. Arthritis Rheum 2000; 43: 901–7.
    Direct Link:
  • 43
    Bengtsson BA, Malmvall BE. An alternate-day corticosteroid regimen in maintenance therapy of giant cell arteritis. Acta Med Scand 1981; 209: 347–50.
    Direct Link:
  • 44
    Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983; 98: 76–85.
  • 45
    Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, et al. Wegener's granulomatosis: an analysis of 158 patients. Ann Intern Med 1992; 116: 488–98.
  • 46
    Kerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci AS, Rottem M, et al. Takayasu arteritis. Ann Intern Med 1994; 120: 919–29.
  • 47
    Van der Veen MJ, Dinant HJ, van Booma-Frankfort C, van Albada-Kuipers GA, Bijlsma JW. Can methotrexate be used as a steroid sparing agent in the treatment of polymyalgia rheumatica and giant cell arteritis? Ann Rheum Dis 1996; 55: 218–23.
  • 48
    De Silva M, Hazleman BL. Azathioprine in giant cell arteritis/polymyalgia rheumatica: a double-blind study. Ann Rheum Dis 1986; 45: 136–8.
  • 49
    Hernandez-Garcia C, Soriano C, Morado C, Ramos P, Fernandez-Gutierrez B, Herrero M, et al. Methotrexate treatment in the management of giant cell arteritis. Scand J Rheumatol 1994; 23: 295–8.
  • 50
    Spiera RF, Mitnick HJ, Kupersmith M, Richmond M, Spiera H, Peterson MG, et al. A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis (GCA). Clin Exp Rheumatol 2001; 19: 495–501.
  • 51
    MacKinnon SK, Starkebaum G, Willkens RF. Pancytopenia associated with low dose pulse methotrexate in the treatment of rheumatoid arthritis. Semin Arthritis Rheum 1985; 15: 119–26.
  • 52
    Walker AM, Funch D, Dreyer NA, Tolman KG, Kremer JM, Alarcon GS, et al. Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis. Arthritis Rheum 1993; 36: 329–35.
    Direct Link:
  • 53
    Alarcon GS, Kremer JM, Macaluso M, Weinblatt ME, Cannon GW, Palmer WR, et al. Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis: a multicenter, case-control study. Ann Intern Med 1997; 127: 356–64.
View Full Article (HTML) Get PDF (105K)