Contributions
Abstract: EP1754
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Natalizumab (NTZ) is a highly effective disease modifying treatment for Relapsing Remitting Multiple Sclerosis (RRMS) often discontinued for safety issues. Potentially disabling disease reactivations are frequently observed following its cessation, even beyond the pre-treatment period level. Despite data from small clinical studies, there is still no consensus regarding the best treatment strategy to be adopted in order to prevent such phenomenon. We present two cases of severe disease reactivation in two RRMS patients treated with monthly administrations of Cyclophosphamide (Cy) after NTZ discontinuation.
Case reports:
Patient 1: a 33 years old woman affected by RRMS since December 2012 started NTZ treatment in April 2013, after two relapses with MRI activity.
Patient 2: a 25 years old woman diagnosed with RRMS in 2009 started NTZ therapy in April 2010, following Mitoxantrone treatment failure. Both patients achieved complete disease remission during NTZ therapy. After respectively 36 and 46 drug administrations they discontinued NTZ due to safety issues and were treated with monthly administrations of Cy (dosage 0,75 gr/m2) after a wash-out period of 2 months. Following the fifth Cy administration, patient 1 developed numbness and hyposthenia in her right limbs. A contrast-enhanced (ce.) brain MRI showed a new 21 mm diameter T2 brain lesion with open-ring Gd enhancement in the white matter of left cerebral hemisphere, consistent with a tumefactive demyelinating lesion. Patient 2 experienced generalized seizure, blurring of vision and right hemiparesis after 3 Cy administrations; ce. MRI showed several new T2 hyperintensities and almost 25 contrast-enhancing lesions in the subcortical and periventricular white matter of cerebral emispheres. Other potential etiologies were ruled out for both patients.
Discussion: Severe clinical and radiological disease reactivations were observed respectively 8 and 5 months following NTZ withdrawal, despite Cy treatment starting after a 2 months washout period. Notably both patients achieved disease remission during NTZ treatment. In conclusion, NTZ is a very effective treatment but its clinical use is restricted by potentially life-threatening infective complications and by the risk of disease reactivation following its withdrawal. The latter represents a still unresolved clinical issue for the MS specialist, needing a safe and more “evidence-based” strategy in order to prevent patient's disability worsening.
Disclosure:
Alice Mariottini received travel funding from Genzyme, Biogen and Novartis
Benedetta Forci received travel funding from Genzyme, Biogen and Novartis
Eliana Magnani received travel funding from Novartis.
Luca Massacesi received educational grants for participation in international meetings from Biogen, Teva, Merk-Serono, Novartis, Genzyme, Roche; honoraria for symposia, advisory boards, preceptorship, consultations from: Biogen, Teva, Merk-Serono, Novartis, Genzyme, Roche, Mylan.
Annamaria Repice received consulting fees by Merck Serono, Biogen, Novartis, Sanofi-Genzyme and funding for travel from Teva, Biogen, Novartis.
Abstract: EP1754
Type: ePoster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Natalizumab (NTZ) is a highly effective disease modifying treatment for Relapsing Remitting Multiple Sclerosis (RRMS) often discontinued for safety issues. Potentially disabling disease reactivations are frequently observed following its cessation, even beyond the pre-treatment period level. Despite data from small clinical studies, there is still no consensus regarding the best treatment strategy to be adopted in order to prevent such phenomenon. We present two cases of severe disease reactivation in two RRMS patients treated with monthly administrations of Cyclophosphamide (Cy) after NTZ discontinuation.
Case reports:
Patient 1: a 33 years old woman affected by RRMS since December 2012 started NTZ treatment in April 2013, after two relapses with MRI activity.
Patient 2: a 25 years old woman diagnosed with RRMS in 2009 started NTZ therapy in April 2010, following Mitoxantrone treatment failure. Both patients achieved complete disease remission during NTZ therapy. After respectively 36 and 46 drug administrations they discontinued NTZ due to safety issues and were treated with monthly administrations of Cy (dosage 0,75 gr/m2) after a wash-out period of 2 months. Following the fifth Cy administration, patient 1 developed numbness and hyposthenia in her right limbs. A contrast-enhanced (ce.) brain MRI showed a new 21 mm diameter T2 brain lesion with open-ring Gd enhancement in the white matter of left cerebral hemisphere, consistent with a tumefactive demyelinating lesion. Patient 2 experienced generalized seizure, blurring of vision and right hemiparesis after 3 Cy administrations; ce. MRI showed several new T2 hyperintensities and almost 25 contrast-enhancing lesions in the subcortical and periventricular white matter of cerebral emispheres. Other potential etiologies were ruled out for both patients.
Discussion: Severe clinical and radiological disease reactivations were observed respectively 8 and 5 months following NTZ withdrawal, despite Cy treatment starting after a 2 months washout period. Notably both patients achieved disease remission during NTZ treatment. In conclusion, NTZ is a very effective treatment but its clinical use is restricted by potentially life-threatening infective complications and by the risk of disease reactivation following its withdrawal. The latter represents a still unresolved clinical issue for the MS specialist, needing a safe and more “evidence-based” strategy in order to prevent patient's disability worsening.
Disclosure:
Alice Mariottini received travel funding from Genzyme, Biogen and Novartis
Benedetta Forci received travel funding from Genzyme, Biogen and Novartis
Eliana Magnani received travel funding from Novartis.
Luca Massacesi received educational grants for participation in international meetings from Biogen, Teva, Merk-Serono, Novartis, Genzyme, Roche; honoraria for symposia, advisory boards, preceptorship, consultations from: Biogen, Teva, Merk-Serono, Novartis, Genzyme, Roche, Mylan.
Annamaria Repice received consulting fees by Merck Serono, Biogen, Novartis, Sanofi-Genzyme and funding for travel from Teva, Biogen, Novartis.