PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
 
Ann Rheum Dis. 1997 August; 56(8): 481–487.
PMCID: PMC1752422

Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide

Abstract

OBJECTIVE—To review our experience with low dose intravenous pulse cyclophosphamide in the treatment of patients with severe connective tissue diseases.
PATIENTS—Ninety patients (68F:22M) with severe connective tissue diseases received a total of 883 cyclophosphamide pulses with 78 of 90 patients initially having weekly 500 mg pulses for a median of three (2-10) weeks. Diagnoses included: systemic lupus erythematosus (SLE) (n=43); systemic vasculitides (n=42); idiopathic inflammatory myopathies (n=4); mixed essential cryoglobulinaemic vasculitis (n=1). The median age was 48 (range 22-76) years with a median disease duration of 94 (18-250) months.
RESULTS—Complete or partial remission was noted in 68 of 90 patients (75.5%) after a median follow up of 56 (5-213) months. At follow up significant median changes were noted in SLE patients: erythrocyte sedimentation rate (ESR) from 44 to 22 mm 1st hour; anti-dsDNA antibody concentrations from 81 to 48 IU/ml; proteinuria from 2.5 to 1.5 g/day; serum albumin from 36 to 40 g/l; complement C3 from 0.88 to 0.90 g/l, and C4 from 0.18 to 0.22 g/l. In the vasculitis patients significant median changes were seen in: ESR from 44 to 15 mm 1st hour; C reactive protein (CRP) from 16 to 5 g/dl; neutrophils from 8.55 to 4.3 × 109/l; platelets from 340 to 261 × 103/l, and haemoglobin from 12.6 to 13.2 g/dl. Patients with Churg-Strauss syndrome, Wegener's granulomatosis, and neuropsychiatric lupus showed the best initial response but 58% of Wegener's patients relapsed. Median corticosteroid doses were significantly reduced from 15 (5-60) mg to 10 (3-35) mg daily. Adverse events: infections (7 patients), neutropenia (5), lymphopenia (18), and haemorrhagic cystitis (1 intravenous and 2 oral cyclophosphamide), allergies to mesna (2). None of the women at risk had prolonged amenorrhoea. Five patients doubled their serum creatinine and five died from sepsis (2) or severe disease (3).
CONCLUSION—Treatment of severe connective tissue diseases with `low dose' intravenous cyclophosphamide pulses compares in efficacy with the higher monthly doses previously advocated. Treatment was well tolerated with fewer adverse effects and most significantly, there were no cases of premature ovarian failure.

Full Text

The Full Text of this article is available as a PDF (112K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • WALTON EW. Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis). Br Med J. 1958 Aug 2;2(5091):265–270. [PMC free article] [PubMed]
  • 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 Jan;98(1):76–85. [PubMed]
  • Fauci AS, Wolff SM. Wegener's granulomatosis: studies in eighteen patients and a review of the literature. Medicine (Baltimore) 1973 Nov;52(6):535–561. [PubMed]
  • Hollander D, Manning RT. The use of alkylating agents in the treatment of Wegener's granulomatosis. Ann Intern Med. 1967 Aug;67(2):393–398. [PubMed]
  • Fauci AS, Katz P, Haynes BF, Wolff SM. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med. 1979 Aug 2;301(5):235–238. [PubMed]
  • Bombardieri S, Hughes GR, Neri R, Del Bravo P, Del Bono L. Cyclophosphamide in severe polymyositis. Lancet. 1989 May 20;1(8647):1138–1139. [PubMed]
  • Balow JE, Austin HA, 3rd, Tsokos GC, Antonovych TT, Steinberg AD, Klippel JH. NIH conference. Lupus nephritis. Ann Intern Med. 1987 Jan;106(1):79–94. [PubMed]
  • Austin HA, 3rd, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, Decker JL. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986 Mar 6;314(10):614–619. [PubMed]
  • Balow JE, Austin HA, 3rd, Muenz LR, Joyce KM, Antonovych TT, Klippel JH, Steinberg AD, Plotz PH, Decker JL. Effect of treatment on the evolution of renal abnormalities in lupus nephritis. N Engl J Med. 1984 Aug 23;311(8):491–495. [PubMed]
  • Steinberg AD, Steinberg SC. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum. 1991 Aug;34(8):945–950. [PubMed]
  • Scott DG, Bacon PA. Intravenous cyclophosphamide plus methylprednisolone in treatment of systemic rheumatoid vasculitis. Am J Med. 1984 Mar;76(3):377–384. [PubMed]
  • Haga HJ, D'Cruz D, Asherson R, Hughes GR. Short term effects of intravenous pulses of cyclophosphamide in the treatment of connective tissue disease crisis. Ann Rheum Dis. 1992 Jul;51(7):885–888. [PMC free article] [PubMed]
  • Houssiau FA, D'Cruz DP, Haga HJ, Hughes GR. Short course of weekly low-dose intravenous pulse cyclophosphamide in the treatment of lupus nephritis: a preliminary study. Lupus. 1991 Nov;1(1):31–35. [PubMed]
  • Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. [PubMed]
  • Hunder GG, Arend WP, Bloch DA, Calabrese LH, Fauci AS, Fries JF, Leavitt RY, Lie JT, Lightfoot RW, Jr, Masi AT, et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Introduction. Arthritis Rheum. 1990 Aug;33(8):1065–1067. [PubMed]
  • Tzioufas AG, Manoussakis MN, Drosos AA, Silis G, Gharavi AE, Moutsopoulos HM. Enzyme immunoassays for the detection of IgG and IgM anti-dsDNA antibodies: clinical significance and specificity. Clin Exp Rheumatol. 1987 Jul-Sep;5(3):247–253. [PubMed]
  • Bryant BM, Jarman M, Ford HT, Smith IE. Prevention of isophosphamide-induced urothelial toxicity with 2-mercaptoethane sulphonate sodium (mesnum) in patients with advanced carcinoma. Lancet. 1980 Sep 27;2(8196):657–659. [PubMed]
  • D'Cruz D, Payne H, Timothy A, Hughes GR. Response of cyclophosphamide-resistant Wegener's granulomatosis to etoposide. Lancet. 1992 Aug 15;340(8816):425–426. [PubMed]
  • Cupps TR, Edgar LC, Fauci AS. Suppression of human B lymphocyte function by cyclophosphamide. J Immunol. 1982 Jun;128(6):2453–2457. [PubMed]
  • Clements PJ, Davis J. Cytotoxic drugs: their clinical application to the rheumatic diseases. Semin Arthritis Rheum. 1986 May;15(4):231–254. [PubMed]
  • Stillwell TJ, Benson RC, Jr, DeRemee RA, McDonald TJ, Weiland LH. Cyclophosphamide-induced bladder toxicity in Wegener's granulomatosis. Arthritis Rheum. 1988 Apr;31(4):465–470. [PubMed]
  • Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992 Mar 15;116(6):488–498. [PubMed]
  • Boumpas DT, Austin HA, 3rd, Vaughan EM, Yarboro CH, Klippel JH, Balow JE. Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med. 1993 Sep 1;119(5):366–369. [PubMed]
  • Zonzits E, Aberer W, Tappeiner G. Drug eruptions from mesna. After cyclophosphamide treatment of patients with systemic lupus erythematosus and dermatomyositis. Arch Dermatol. 1992 Jan;128(1):80–82. [PubMed]
  • Boumpas DT, Austin HA, 3rd, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, Balow JE. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet. 1992 Sep 26;340(8822):741–745. [PubMed]
  • Belmont HM, Storch M, Buyon J, Abramson S. New York University/Hospital for Joint Diseases experience with intravenous cyclophosphamide treatment: efficacy in steroid unresponsive lupus nephritis. Lupus. 1995 Apr;4(2):104–108. [PubMed]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group