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OP0238 The Effect of Cyclophosphamide and Rituximab for Remission Induction and Maintenance in Severe Anca-Associated Vasculitis on Immunoglobulin Levels: Repeat Cycles on Clinical Relapse with Rituximab are Associated with Stable IGA and IGG
  1. M.Y. Md Yusof1,2,
  2. M.-I. Porto1,
  3. J. Andrews1,2,
  4. S. Dass1,2,
  5. S. Savic3,
  6. E.M. Vital1,4,
  7. P. Emery1,2
  1. 1Rheumatology, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds
  2. 2Rheumatology
  3. 3Immunology, NIHR Leeds Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds
  4. 4Rheumatology, NIHR Leeds Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Greater Manchester, United Kingdom

Abstract

Background Remission induction can be achieved using either rituximab (RTX) or cyclophosphamide (CyP) in severe ANCA-associated vasculitis (AAV). Initial safety of these therapies is similar but long term data are more limited. Repeat cycles of RTX using fixed-interval retreatment may lead to hypogammaglobulinaemia [1] and severe infection [2]. Detailed immunoglobulin (Ig) levels using a less frequent on-demand retreatment schedule; has not been reported.

Objectives To evaluate (i) the effect of CyP and RTX on serum Ig levels and (ii) report the incidence of serious infections after repeat cycles of RTX on clinical relapse in AAV.

Methods We studied patients with severe AAV treated with pulsed intravenous CyP and/or RTX for remission induction and maintenance in a single centre between January 2004 and September 2014 (Total follow-up: 221.7 patient-years). Each cycle of RTX consisted of 2x1000mg infusions repeated on clinical relapse. IgM, IgA and IgG levels were measured at baseline and 6 months after each cycle. Serious infections were those resulting in hospitalisation for more than 24 hours or required intravenous antibiotics.

Results 62 patients (32 male and 30 female; median age prior to CyP: 52 (range 18-80)) who received remission induction with CyP and had Ig data were studied. Of these, 46 (74%) relapsed and then received RTX. An additional 5 patients who received RTX as first-line remission induction therapy were also included in the RTX group. Treatment with CyP resulted in a decrease in levels of all Ig classes; median (IQR) IgM reduced from 1.13 (0.68-1.44) to 0.74 (0.49-1.14), IgA from 2.45 (1.70-3.01) to 1.65 (1.1-2.3) and IgG from 13.6 (11.2-15.9) to 7.7 (6.1-9.9) g/L; all p<0.001 at 6 months. Levels remained below the CyP baseline at 36 months. Median time to re-treatment for cycles 1-5 were 87, 71, 61, 57 and 61 weeks respectively. There were no progressive deterioration in IgA and IgG levels measured at 6-months of each cycle compared to RTX baseline (p=0.99 and 0.84 respectively) but a reduction in IgM (p<0.001). 7 patients had low IgG (normal range 6.0-16.0 g/L) before RTX and only 4 (11%) developed new low IgG during therapy. 1 patient with low IgG at baseline had two serious infections and required intravenous immunoglobulin. No other patient had to discontinue RTX due to low IgG. 14 serious infections were recorded (6.31/100 patient-years).

Conclusions Remission induction with CyP led to a decline in immunoglobulin levels. Following a relapse and subsequent RTX therapy using retreatment on clinical relapse, IgA and IgG remained stable and serious infection rates were low over a long period of follow-up. Repeat cycles of RTX appear safe when used on demand and effect on IgG is not worse than CyP.

References

  1. Smith et al. Arthritis Rheum 2012.

  2. Besada et al. Rheumatology 2013.

  3. Besada et al. Rheumatology 2014.

Disclosure of Interest None declared

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