Contributions
Abstract: P1142
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Cladribine tablets given annually for 2 years in short-duration courses showed efficacy in a spectrum of patients with relapsing multiple sclerosis. The most common adverse event (AE) was lymphopenia, reflecting the mode of action of cladribine. An integrated analysis of safety showed that the incidence of infections overall was not higher in patients receiving cladribine tablets 3.5 mg/kg than in patients receiving placebo, except for a small increased risk of herpes zoster.
Objective: This post-hoc analysis examined the infectious AEs occurring during exact periods of Grade 3 or 4 lymphopenia in patients treated with cladribine tablets 3.5 mg/kg; previous analyses used recovery to Grade 1 or better.
Methods: A monotherapy oral cohort was derived from CLARITY, CLARITY Extension, ORACLE-MS and the PREMIERE registry, with 923 patients receiving cladribine tablets 3.5 mg/kg. The AE profile for cladribine tablets 3.5 mg/kg during the exact periods of Grade 3 or 4 lymphopenia was analysed (the onset of the Grade 3 or 4 lymphopenia to first Grade 2 or lower plus 2 weeks). Adjusted AE incidences per 100 patient years (Adj-AE per 100PY) were calculated.
Results: Adj-AE per 100PY for any infections and infestations during periods of Grade 3 or 4 lymphopenia (with G3/4) was 57.53 vs 24.50 outside these periods (without G3/4). Types of infectious AEs with G3/4 were similar to without G3/4 and did not show any specific pattern. More than half of cases occurring with G3/4 were easily-treatable infections of the upper respiratory tract (Adj-AE per 100PY: nasopharyngitis, 13.48 vs 5.24 without G3/4; upper respiratory tract infection, 9.67 vs 3.41 without G3/4; pharyngitis; 4.51 vs 0.73 without G3/4). Herpes zoster was reported in 4 patients with G3/4 (Adj AE per 100PY 4.50 vs 0.73 without G3/4); cases were dermatomal and mild to moderate in severity. Single occurrences were reported for most infectious AEs. Opportunistic infections were single occurrences of 'urinary tract infection fungal' and 'fungal infection' (preferred terms) and neither was severe or serious. There were no opportunistic infections that were difficult to treat.
Conclusions: Severe lymphopenia resulted in an increased frequency of infections but did not have any differential effect on the type of infectious AEs in patients treated with cladribine tablets 3.5 mg/kg monotherapy. The profile of herpes zoster was uncomplicated, consistent with the findings of previous safety analyses.
Disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
SC: has received honoraria for lectures/consultations from Merck, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, TEVA, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, TEVA Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
TL: is a consultant to EMD Serono, Teva Neuroscience, Biogen, Bayer, Pfizer; and is involved in clinical trials sponsored by EMD Serono, Teva Neuroscience, Bayer, ONO, Novartis, Daiichi, Acorda.
GC: has received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, Receptors, Biogen Idec, Genentech-Roche, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck Serono, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptors, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
XM: has received speaker honoraria and travel expenses for scientific meetings, steering committee member, and advisory board member of clinical trials for Bayer Schering Pharma, Biogen Idec, EMD Serono, Genentech, Genzyme, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
ES and CH: are employees of Merck KGaA, Darmstadt, Germany.
FD: is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.
Abstract: P1142
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Cladribine tablets given annually for 2 years in short-duration courses showed efficacy in a spectrum of patients with relapsing multiple sclerosis. The most common adverse event (AE) was lymphopenia, reflecting the mode of action of cladribine. An integrated analysis of safety showed that the incidence of infections overall was not higher in patients receiving cladribine tablets 3.5 mg/kg than in patients receiving placebo, except for a small increased risk of herpes zoster.
Objective: This post-hoc analysis examined the infectious AEs occurring during exact periods of Grade 3 or 4 lymphopenia in patients treated with cladribine tablets 3.5 mg/kg; previous analyses used recovery to Grade 1 or better.
Methods: A monotherapy oral cohort was derived from CLARITY, CLARITY Extension, ORACLE-MS and the PREMIERE registry, with 923 patients receiving cladribine tablets 3.5 mg/kg. The AE profile for cladribine tablets 3.5 mg/kg during the exact periods of Grade 3 or 4 lymphopenia was analysed (the onset of the Grade 3 or 4 lymphopenia to first Grade 2 or lower plus 2 weeks). Adjusted AE incidences per 100 patient years (Adj-AE per 100PY) were calculated.
Results: Adj-AE per 100PY for any infections and infestations during periods of Grade 3 or 4 lymphopenia (with G3/4) was 57.53 vs 24.50 outside these periods (without G3/4). Types of infectious AEs with G3/4 were similar to without G3/4 and did not show any specific pattern. More than half of cases occurring with G3/4 were easily-treatable infections of the upper respiratory tract (Adj-AE per 100PY: nasopharyngitis, 13.48 vs 5.24 without G3/4; upper respiratory tract infection, 9.67 vs 3.41 without G3/4; pharyngitis; 4.51 vs 0.73 without G3/4). Herpes zoster was reported in 4 patients with G3/4 (Adj AE per 100PY 4.50 vs 0.73 without G3/4); cases were dermatomal and mild to moderate in severity. Single occurrences were reported for most infectious AEs. Opportunistic infections were single occurrences of 'urinary tract infection fungal' and 'fungal infection' (preferred terms) and neither was severe or serious. There were no opportunistic infections that were difficult to treat.
Conclusions: Severe lymphopenia resulted in an increased frequency of infections but did not have any differential effect on the type of infectious AEs in patients treated with cladribine tablets 3.5 mg/kg monotherapy. The profile of herpes zoster was uncomplicated, consistent with the findings of previous safety analyses.
Disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
SC: has received honoraria for lectures/consultations from Merck, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, TEVA, and Actinobac Biomed Inc.; has served on advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, TEVA Pharmaceuticals, and Biogen Idec; and received grant support from Bayer HealthCare.
TL: is a consultant to EMD Serono, Teva Neuroscience, Biogen, Bayer, Pfizer; and is involved in clinical trials sponsored by EMD Serono, Teva Neuroscience, Bayer, ONO, Novartis, Daiichi, Acorda.
GC: has received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd., Sanofi-Aventis, Merck, Receptors, Biogen Idec, Genentech-Roche, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck Serono, Biogen Dompè, Bayer Schering, and Serono Symposia International Foundation; and trial grant support from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Receptors, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè, and Bayer Schering.
XM: has received speaker honoraria and travel expenses for scientific meetings, steering committee member, and advisory board member of clinical trials for Bayer Schering Pharma, Biogen Idec, EMD Serono, Genentech, Genzyme, Novartis, Roche, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
ES and CH: are employees of Merck KGaA, Darmstadt, Germany.
FD: is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.