Contributions
Abstract: EP1740
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Potential adverse events associated with alemtuzumab (AL) therapy for relapsing multiple sclerosis (MS) include secondary autoimmune disorders of which autoimmune nephropathies, including anti-glomerular basement membrane (GBM) disease, have been identified in 0.3% of cases. It is unclear if recommended pharmacovigilance for AL involving monthly blood and urine testing for 4 years from last AL infusion would identify anti-GBM disease in an asymptomatic state.
Objectives: To report a rare case of AL-associated anti-GBM Ab positive glomerulonephritis (GN) with unusual complications.
Case description: A 30-year-old female with highly active MS was treated first-line with two standard courses of AL (total dose 96mg) 1 year apart. Urine testing and serum creatinine were normal 6 weeks and 3 weeks prior to symptom onset respectively. 5 months after last AL infusion, she presented with a 5-day history of headache, vomiting and oliguria. There was no rash, arthralgia or haemoptysis. Urine showed proteinuria, haematuria and granular casts; serum creatinine was raised (492 umol/l). Renal biopsy showed extensive necrotising and crescentic lesions. Anti-GBM Ab titre was markedly raised (463 EliAu/ml). Extensive microbial testing was negative. Cerebrospinal fluid testing was normal.
To date, the patient has been treated with 20 sessions of plasma exchange, 2 courses of rituximab 375mg/m2, intravenous methylprednisolone and oral prednisolone with slow taper. 3 weeks from symptom onset, the patient developed fever, headache, visual field defect, severe hypertension and seizures. Magnetic resonance imaging of brain was indicative of posterior reversible encephalopathy syndrome (PRES). Within 24 hours, platelet count dropped to nadir 64X109/l with haemoglobin 8.1g/dl, schistocytes on blood film, increased reticulocytes and reduced haptoglobins, suggestive of haemolytic anaemia. Normal ADAMTS13 activity (70iu/dl) supported a diagnosis of secondary thrombotic microangiopathy. She remains dialysis-dependent with persistently elevated anti-GBM Ab titres
(mean 280 EliAu/ml).
Conclusion: Failure to detect imminent symptomatic manifestation of AL-associated anti-GBM disease with monthly blood and urine reminds us that although safety monitoring may detect other autoimmune complications such as thyroid disease, it may not identify an explosive onset disorder such as anti-GBM disease. New clinical symptoms should prompt consideration of these disorders.
Disclosure:
SMY has received a Newman Research Fellowship sponsored by Novartis.
NMcN has received a Newman Research Fellowship sponsored by Biogen.
SO'R has nothing to disclose.
JF has nothing to disclose.
AW has nothing to disclose.
CMcG has received research funding and/or honoraria from Bayer, Biogen, Genzyme, Novartis, Roche and Teva.
Abstract: EP1740
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Potential adverse events associated with alemtuzumab (AL) therapy for relapsing multiple sclerosis (MS) include secondary autoimmune disorders of which autoimmune nephropathies, including anti-glomerular basement membrane (GBM) disease, have been identified in 0.3% of cases. It is unclear if recommended pharmacovigilance for AL involving monthly blood and urine testing for 4 years from last AL infusion would identify anti-GBM disease in an asymptomatic state.
Objectives: To report a rare case of AL-associated anti-GBM Ab positive glomerulonephritis (GN) with unusual complications.
Case description: A 30-year-old female with highly active MS was treated first-line with two standard courses of AL (total dose 96mg) 1 year apart. Urine testing and serum creatinine were normal 6 weeks and 3 weeks prior to symptom onset respectively. 5 months after last AL infusion, she presented with a 5-day history of headache, vomiting and oliguria. There was no rash, arthralgia or haemoptysis. Urine showed proteinuria, haematuria and granular casts; serum creatinine was raised (492 umol/l). Renal biopsy showed extensive necrotising and crescentic lesions. Anti-GBM Ab titre was markedly raised (463 EliAu/ml). Extensive microbial testing was negative. Cerebrospinal fluid testing was normal.
To date, the patient has been treated with 20 sessions of plasma exchange, 2 courses of rituximab 375mg/m2, intravenous methylprednisolone and oral prednisolone with slow taper. 3 weeks from symptom onset, the patient developed fever, headache, visual field defect, severe hypertension and seizures. Magnetic resonance imaging of brain was indicative of posterior reversible encephalopathy syndrome (PRES). Within 24 hours, platelet count dropped to nadir 64X109/l with haemoglobin 8.1g/dl, schistocytes on blood film, increased reticulocytes and reduced haptoglobins, suggestive of haemolytic anaemia. Normal ADAMTS13 activity (70iu/dl) supported a diagnosis of secondary thrombotic microangiopathy. She remains dialysis-dependent with persistently elevated anti-GBM Ab titres
(mean 280 EliAu/ml).
Conclusion: Failure to detect imminent symptomatic manifestation of AL-associated anti-GBM disease with monthly blood and urine reminds us that although safety monitoring may detect other autoimmune complications such as thyroid disease, it may not identify an explosive onset disorder such as anti-GBM disease. New clinical symptoms should prompt consideration of these disorders.
Disclosure:
SMY has received a Newman Research Fellowship sponsored by Novartis.
NMcN has received a Newman Research Fellowship sponsored by Biogen.
SO'R has nothing to disclose.
JF has nothing to disclose.
AW has nothing to disclose.
CMcG has received research funding and/or honoraria from Bayer, Biogen, Genzyme, Novartis, Roche and Teva.