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Ann Rheum Dis 1997;56:481-487 doi:10.1136/ard.56.8.481
  • Extended reports

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

  1. Ignacio Martin-Suareza,
  2. David D’Cruzb,
  3. Mohammed Mansoora,
  4. Ana Paula Fernandesa,
  5. Munther A Khamashtaa,
  6. Graham R V Hughesa
  1. aLupus Arthritis Research Unit, The Rayne Institute, St Thomas’s Hospital, London , bRoyal Hospitals Trust, London
  1. Dr M A Khamashta, Lupus Arthritis Research Unit, The Rayne Institute, St Thomas’s Hospital, London SE1 7EH.
  • Accepted 6 June 1997

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.

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