Alemtuzumab as Remission Induction Therapy in Behçet Disease: A 20-year Experience.
OBJECTIVE
To study the efficacy and safety of anti-CD52 antibody (alemtuzumab) in the treatment of refractory and relapsing Behçet disease (BD).


METHODS
Thirty-two patients (22 women) with BD received 60 courses of alemtuzumab between 1994 and 2013. Three-dose regimens were used: 134 mg in 21 courses (Group 1), 95 mg in 18 courses (Group 2), and 60 mg in 21 courses (Group 3). Immunosuppressive drugs were stopped at the time of alemtuzumab, and prednisolone was reduced according to clinical response. Treatment response was assessed by clinical status, inflammatory activity, prednisolone dose, and the need for subsequent immunosuppressive drugs and disease relapse.


RESULTS
After the first alemtuzumab course, 27 of 32 patients (84%) achieved partial or complete remission (CR). Fifty of 60 courses (83%) resulted in remission (66% CR) without differences in remission rates between dosing regimens. Profound lymphocyte depletion occurred after all courses. Relapse-free survival rates were 83.6% at 6 months and 52.8% at 12 months, and were higher among Group 1 patients (Group 1: 100% and 77.8%, Group 2: 81.3% and 37.5%, and Group 3: 65.0% and 37.1%, p < 0.001). Mild to moderate infusion reactions occurred after 16 courses (27%). Eight patients (25%) developed symptomatic thyroid disease.


CONCLUSIONS
Alemtuzumab led to remission in the majority of patients with difficult-to-treat BD. Relapse was common and may be associated with lower dosing. Adverse events included infusion reactions and new autoimmunity. Achieving complete lymphocyte depletion did not affect the remission rate or duration.
From the Department of Renal Medicine, Addenbrooke's Hospital, Cambridge, UK; Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden; Department of Medicine, Hospital Pantai Ayer Keroh, Melaka, Malaysia.A.J. Mohammad, MD, PhD, Department of Renal Medicine, Addenbrooke's Hospital, and Department of Clinical Sciences, Rheumatology, Lund University; R.M. Smith, MA, MB BChir, MRCP, Department of Renal Medicine, Addenbrooke's Hospital; Y.W. Chow, MD(USM), MRCP( UK), MRCPE, FRCP(Edinburgh), AM(MAL), Department of Medicine, Hospital Pantai Ayer Keroh Melaka; A.N. Chaudhry, MBBS, PhD, FRCP, FHEA, FACad MEd, Department of Renal Medicine, Addenbrooke's Hospital; D.R. Jayne, MD, FRCP, Department of Renal Medicine, Addenbrooke's Hospital. aladdin.mohammad@med.lu.se.
Aladdin J
AJ
Mohammad
From the Department of Renal Medicine, Addenbrooke's Hospital, Cambridge, UK; Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden; Department of Medicine, Hospital Pantai Ayer Keroh, Melaka, Malaysia.A.J. Mohammad, MD, PhD, Department of Renal Medicine, Addenbrooke's Hospital, and Department of Clinical Sciences, Rheumatology, Lund University; R.M. Smith, MA, MB BChir, MRCP, Department of Renal Medicine, Addenbrooke's Hospital; Y.W. Chow, MD(USM), MRCP( UK), MRCPE, FRCP(Edinburgh), AM(MAL), Department of Medicine, Hospital Pantai Ayer Keroh Melaka; A.N. Chaudhry, MBBS, PhD, FRCP, FHEA, FACad MEd, Department of Renal Medicine, Addenbrooke's Hospital; D.R. Jayne, MD, FRCP, Department of Renal Medicine, Addenbrooke's Hospital.
Rona M
RM
Smith
From the Department of Renal Medicine, Addenbrooke's Hospital, Cambridge, UK; Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden; Department of Medicine, Hospital Pantai Ayer Keroh, Melaka, Malaysia.A.J. Mohammad, MD, PhD, Department of Renal Medicine, Addenbrooke's Hospital, and Department of Clinical Sciences, Rheumatology, Lund University; R.M. Smith, MA, MB BChir, MRCP, Department of Renal Medicine, Addenbrooke's Hospital; Y.W. Chow, MD(USM), MRCP( UK), MRCPE, FRCP(Edinburgh), AM(MAL), Department of Medicine, Hospital Pantai Ayer Keroh Melaka; A.N. Chaudhry, MBBS, PhD, FRCP, FHEA, FACad MEd, Department of Renal Medicine, Addenbrooke's Hospital; D.R. Jayne, MD, FRCP, Department of Renal Medicine, Addenbrooke's Hospital.
Yok W
YW
Chow
From the Department of Renal Medicine, Addenbrooke's Hospital, Cambridge, UK; Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden; Department of Medicine, Hospital Pantai Ayer Keroh, Melaka, Malaysia.A.J. Mohammad, MD, PhD, Department of Renal Medicine, Addenbrooke's Hospital, and Department of Clinical Sciences, Rheumatology, Lund University; R.M. Smith, MA, MB BChir, MRCP, Department of Renal Medicine, Addenbrooke's Hospital; Y.W. Chow, MD(USM), MRCP( UK), MRCPE, FRCP(Edinburgh), AM(MAL), Department of Medicine, Hospital Pantai Ayer Keroh Melaka; A.N. Chaudhry, MBBS, PhD, FRCP, FHEA, FACad MEd, Department of Renal Medicine, Addenbrooke's Hospital; D.R. Jayne, MD, FRCP, Department of Renal Medicine, Addenbrooke's Hospital.
Afzal N
AN
Chaudhry
From the Department of Renal Medicine, Addenbrooke's Hospital, Cambridge, UK; Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden; Department of Medicine, Hospital Pantai Ayer Keroh, Melaka, Malaysia.A.J. Mohammad, MD, PhD, Department of Renal Medicine, Addenbrooke's Hospital, and Department of Clinical Sciences, Rheumatology, Lund University; R.M. Smith, MA, MB BChir, MRCP, Department of Renal Medicine, Addenbrooke's Hospital; Y.W. Chow, MD(USM), MRCP( UK), MRCPE, FRCP(Edinburgh), AM(MAL), Department of Medicine, Hospital Pantai Ayer Keroh Melaka; A.N. Chaudhry, MBBS, PhD, FRCP, FHEA, FACad MEd, Department of Renal Medicine, Addenbrooke's Hospital; D.R. Jayne, MD, FRCP, Department of Renal Medicine, Addenbrooke's Hospital.
David R W
DR
Jayne
D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001528:Behcet Syndrome / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D012074:Remission Induction / Q000379:methods; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab
ALEMTUZUMAB; BEHÇET DISEASE; LYMPHOCYTE DEPLETION THERAPY; REMISSION INDUCTION; THYROID DISEASE