PMID- 35713731
OWN - NLM
STAT- MEDLINE
DCOM- 20220819
LR  - 20220822
IS  - 1590-3478 (Electronic)
IS  - 1590-1874 (Linking)
VI  - 43
IP  - 9
DP  - 2022 Sep
TI  - Comparative safety of high-efficacy disease-modifying therapies in 
      relapsing-remitting multiple sclerosis: a systematic review and network 
      meta-analysis.
PG  - 5479-5500
LID - 10.1007/s10072-022-06197-3 [doi]
AB  - OBJECTIVE: This study aimed to compare the safety profile of high-efficacy 
      disease-modifying therapies (DMTs) natalizumab, fingolimod, alemtuzumab, 
      cladribine, ocrelizumab, ofatumumab, ozanimod, as well as a potentially 
      high-efficacy DMT, ponesimod, in adult patients with relapsing-remitting multiple 
      sclerosis (RRMS). METHODS: A systematic review with frequentist network 
      meta-analysis (NMA) was performed according to the Preferred Reporting Items for 
      Systematic Reviews and Meta-analyses (PRISMA) guidelines. We included randomized 
      controlled trials (RCTs) with at least 48-week follow-up investigating the use of 
      natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab, ofatumumab, 
      ozanimod, and ponesimod, as well as other DMTs, in adult patients with RRMS. 
      Eligible studies were identified by two reviewers in MEDLINE (via PubMed), 
      EMBASE, and Cochrane Library. The Cochrane Collaboration tool to assess the risk 
      of bias for RCTs was used. RESULTS: A total of 33 RCTs were included in the 
      systematic review and NMA. A higher rate of adverse events (AEs) was revealed for 
      alemtuzumab versus all other high-efficacy DMTs; for alemtuzumab (average 
      probability of an event: 98.2%) versus placebo (86.2%); for cladribine (3.5 mg; 
      90.5%) versus ozanimod (1 mg; 84.2%) and placebo; as well as for ocrelizumab 
      (95.5%) versus ozanimod, ofatumumab (88.9%), fingolimod (87.4%), natalizumab 
      (82.8%), and placebo. No significant differences were found between drugs in 
      terms of serious AEs except for cladribine (3.5 mg, 17.3%) versus ocrelizumab 
      (10.3%) and ofatumumab (16.6%) versus ocrelizumab. Significant differences in AEs 
      leading to the discontinuation of study drug were found only for ponesimod 
      (10.1%) versus alemtuzumab (12 mg, 3.0%) and placebo (4.2%). No differences were 
      found in terms of upper respiratory tract infections, nasopharyngitis, fatigue, 
      and nausea between individual high-efficacy DMTs as well as between DMTs and 
      placebo. The results of the NMA indicated a higher risk of infections for 
      alemtuzumab (12 mg) versus ocrelizumab, for cladribine (3.5 mg) versus ofatumumab 
      and placebo, and for ofatumumab versus placebo. For serious infections and 
      urinary tract infections, a significant increase was found only for alemtuzumab 
      (12 mg) versus ocrelizumab, while no differences were found between the other 
      DMTs or between DMTs and placebo. Headache was more common for alemtuzumab 
      (12 mg) as compared with all the other high-efficacy DMTs and placebo, as well as 
      for cladribine versus natalizumab and fingolimod versus natalizumab. CONCLUSION: 
      The commonly reported AEs are generally similar among high-efficacy DMTs. 
      However, based on P scores for most analyzed endpoints, natalizumab and 
      ocrelizumab were shown to be the safest DMTs. Considering the limitations of 
      indirect comparisons, further research is needed to confirm our findings, 
      preferably head-to-head RCTs and large observational studies.
CI  - (c) 2022. Fondazione Societa Italiana di Neurologia.
FAU - Sladowska, Katarzyna
AU  - Sladowska K
AD  - Department of Nutrition and Drug Research, Faculty of Health Sciences, Institute 
      of Public Health, Jagiellonian University Medical College, Krakow, Poland.
FAU - Kawalec, Pawel
AU  - Kawalec P
AUID- ORCID: 0000-0002-0125-0947
AD  - Department of Nutrition and Drug Research, Faculty of Health Sciences, Institute 
      of Public Health, Jagiellonian University Medical College, Krakow, Poland. 
      pawel.kawalec@uj.edu.pl.
FAU - Holko, Przemyslaw
AU  - Holko P
AD  - Department of Nutrition and Drug Research, Faculty of Health Sciences, Institute 
      of Public Health, Jagiellonian University Medical College, Krakow, Poland.
FAU - Osiecka, Oktawia
AU  - Osiecka O
AD  - Department of Microbiology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Krakow, Poland.
LA  - eng
GR  - N43/DBS/000099./Uniwersytet Jagiellonski Collegium Medicum/
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20220617
PL  - Italy
TA  - Neurol Sci
JT  - Neurological sciences : official journal of the Italian Neurological Society and 
      of the Italian Society of Clinical Neurophysiology
JID - 100959175
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Natalizumab)
RN  - 3A189DH42V (Alemtuzumab)
RN  - 47M74X9YT5 (Cladribine)
RN  - G926EC510T (Fingolimod Hydrochloride)
SB  - IM
MH  - Adult
MH  - Alemtuzumab/adverse effects
MH  - Cladribine/adverse effects
MH  - Fingolimod Hydrochloride/adverse effects
MH  - Humans
MH  - *Immunosuppressive Agents/adverse effects
MH  - *Multiple Sclerosis, Relapsing-Remitting/drug therapy
MH  - Natalizumab/adverse effects
MH  - Network Meta-Analysis
OTO - NOTNLM
OT  - Disease-modifying therapies
OT  - Meta-analysis
OT  - Multiple sclerosis
OT  - Safety
OT  - Systematic review
EDAT- 2022/06/18 06:00
MHDA- 2022/08/20 06:00
CRDT- 2022/06/17 11:16
PHST- 2022/02/08 00:00 [received]
PHST- 2022/06/04 00:00 [accepted]
PHST- 2022/06/18 06:00 [pubmed]
PHST- 2022/08/20 06:00 [medline]
PHST- 2022/06/17 11:16 [entrez]
AID - 10.1007/s10072-022-06197-3 [pii]
AID - 10.1007/s10072-022-06197-3 [doi]
PST - ppublish
SO  - Neurol Sci. 2022 Sep;43(9):5479-5500. doi: 10.1007/s10072-022-06197-3. Epub 2022 
      Jun 17.