Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab.
OBJECTIVE
To describe the effects of switching treatment from ongoing first-line injectable therapies to rituximab on inflammatory activity measured by MRI and levels of CSF neurofilament light chain (CSF-NFL) in a cohort of patients with clinically stable relapsing-remitting multiple sclerosis (RRMS).


METHODS
Seventy-five patients with clinically stable RRMS treated with the first-line injectables interferon-β (IFN-β) and glatiramer acetate (GA) at 3 Swedish centers were switched to rituximab in this open-label phase II multicenter study. After a run-in period of 3 months, 2 IV doses of 1,000 mg rituximab were given 2 weeks apart followed by repeated clinical assessment, MRI, and CSF-NFL for 24 months.


RESULTS
The mean cumulated number of gadolinium-enhancing lesions per patient at months 3 and 6 after treatment shift to rituximab was reduced compared to the run-in period (0.028 vs 0.36, p = 0.029). During the first year after treatment shift, the mean number of new or enlarged T2 lesions per patient was reduced (0.01 vs 0.28, p = 0.004) and mean CSF-NFL levels were reduced by 21% (p = 0.01).


CONCLUSIONS
For patients with RRMS, a treatment switch from IFN or GA to rituximab is associated with reduced inflammatory activity measured by MRI and CSF-NFL.


METHODS
This study provides Class IV evidence that rituximab has an equal or superior effect in reducing inflammatory activity in RRMS measured by MRI and CSF-NFL compared to first-line injectables during the first year after treatment shift.
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. pierre.deflon@regionjh.se.
Pierre
P
de Flon
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Martin
M
Gunnarsson
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Katarina
K
Laurell
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Lars
L
Söderström
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Richard
R
Birgander
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Thomas
T
Lindqvist
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Wolfgang
W
Krauss
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Ann
A
Dring
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Joakim
J
Bergman
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Peter
P
Sundström
From the Department of Pharmacology and Clinical Neuroscience, Unit of Neurology, Östersund (P.d.F., K.L.), Umeå University; Department of Radiation Sciences, Diagnostic Radiology (R.B., T.L.), and Department of Pharmacology and Clinical Neuroscience (A.D., J.B., P.S., A.S.), Umeå University; Department of Neurology, School of Medical Sciences (M.G.), Department of Radiology (W.K.), Faculty of Medicine and Health, Örebro University; Unit of Research, Education and Development (L.S.), Region Jämtland Härjedalen; and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Anders
A
Svenningsson
D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003287:Contrast Media; D004185:Disability Evaluation; D057915:Drug Substitution; D005260:Female; D005500:Follow-Up Studies; D005682:Gadolinium; D000068717:Glatiramer Acetate / Q000008:administration & dosage; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D016899:Interferon-beta / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D000069283:Rituximab / Q000008:administration & dosage*; D013548:Sweden; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D003287:Contrast Media; D007155:Immunologic Factors; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D000069283:Rituximab; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D005682:Gadolinium