PMID- 35377447
OWN - NLM
STAT- MEDLINE
DCOM- 20221201
LR  - 20230315
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Print)
IS  - 1462-0324 (Linking)
VI  - 61
IP  - 12
DP  - 2022 Nov 28
TI  - Safety and efficacy of filgotinib, lanraplenib and tirabrutinib in Sjogren's 
      syndrome: a randomized, phase 2, double-blind, placebo-controlled study.
PG  - 4797-4808
LID - 10.1093/rheumatology/keac167 [doi]
AB  - OBJECTIVE: The aim of this study was to characterize the safety and efficacy of 
      filgotinib, lanraplenib and tirabrutinib in patients with active SS. METHODS: 
      This multicentre, double-blind study randomized patients with active primary or 
      secondary SS [EULAR SS disease activity index (ESSDAI) >/=5) to receive filgotinib 
      200 mg (Janus kinase-1 inhibitor), lanraplenib 30 mg (spleen tyrosine kinase 
      inhibitor), tirabrutinib 40 mg (Bruton's tyrosine kinase inhibitor), or placebo. 
      The composite primary end point was the week-12 proportion of patients fulfilling 
      protocol-specified improvement criteria (based on CRP and SS-related symptoms). 
      The EULAR SS patient-reported index (ESSPRI) and the ESSDAI change from baseline 
      (CFB) were secondary end points. Exploratory end points included disease-related 
      biomarkers. Treatment-emergent adverse events (AEs) represented safety outcomes. 
      RESULTS: The mean of the baseline ESSDAI was 10.1, and of ESSPRI was 6.2 in the 
      150 patients who were treated; 125 completed the 24-week placebo-controlled 
      treatment period. At week 12, 43.3% of the filgotinib group achieved the primary 
      end point (P = 0.17 vs placebo) vs 42.3% (P = 0.16), 34.7% (P = 0.33), and 26.7% 
      of lanraplenib, tirabrutinib, and placebo groups, respectively. Neither secondary 
      end point was met. Biomarker reductions included immunoglobulins classically 
      associated with SS disease activity. Filgotinib ESSDAI CFB appeared more 
      pronounced in subgroups with baseline ESSDAI >/=14 or without DMARDs/CSs. Most AEs 
      were Grade 1 or 2. CONCLUSION: Three drugs with disparate mechanisms were tested, 
      but no significant differences vs placebo in primary or secondary end points were 
      observed. These results may be considered hypothesis-generating, given the drug 
      tolerability, subgroup analysis, and biomarker findings. TRIAL REGISTRATION: 
      ClinicalTrials.gov, https://clinicaltrials.gov, NCT03100942.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology.
FAU - Price, Elizabeth
AU  - Price E
AD  - Department of Rheumatology, Great Western Hospital, Swindon.
FAU - Bombardieri, Michele
AU  - Bombardieri M
AD  - Centre for Experimental Medicine and Rheumatology, William Harvey Research 
      Institute, Queen Mary University of London, London.
FAU - Kivitz, Alan
AU  - Kivitz A
AD  - Altoona Center for Clinical Research, Duncansville, PA.
FAU - Matzkies, Franziska
AU  - Matzkies F
AD  - Clinical Research.
FAU - Gurtovaya, Oksana
AU  - Gurtovaya O
AD  - Biostatistics.
FAU - Pechonkina, Alena
AU  - Pechonkina A
AD  - Clinical Research.
FAU - Jiang, Wendy
AU  - Jiang W
AD  - Bioinformatics, Gilead Sciences, Inc., Foster City, CA.
FAU - Downie, Bryan
AU  - Downie B
AD  - Bioinformatics, Gilead Sciences, Inc., Foster City, CA.
FAU - Mathur, Anubhav
AU  - Mathur A
AD  - Clinical Research.
FAU - Mozaffarian, Afsaneh
AU  - Mozaffarian A
AD  - Clinical Research.
FAU - Mozaffarian, Neelufar
AU  - Mozaffarian N
AD  - Immunology Research & Development, Janssen Pharmaceuticals, Cambridge, MA, USA.
FAU - Gottenberg, J Eric
AU  - Gottenberg JE
AD  - Hopitaux Universitaires de Strasbourg et Universite de Strasbourg, and Centre de 
      Reference pour les Maladies Auto-Immunes Systemiques Rares, CNRS, IBMC, UPR3572, 
      Strasbourg, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT03100942
GR  - MR/N003063/1/MRC_/Medical Research Council/United Kingdom
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (GLPG0634)
RN  - LXG44NDL2T (tirabrutinib)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - *Sjogren's Syndrome/diagnosis
MH  - Double-Blind Method
MH  - Severity of Illness Index
MH  - Protein Kinase Inhibitors/adverse effects
MH  - Biomarkers
MH  - Treatment Outcome
PMC - PMC9707320
OTO - NOTNLM
OT  - Sjogren's syndrome
OT  - efficacy
OT  - filgotinib
OT  - lanraplenib
OT  - randomized trial
OT  - safety
OT  - tirabrutinib
EDAT- 2022/04/05 06:00
MHDA- 2022/12/02 06:00
PMCR- 2022/04/04
CRDT- 2022/04/04 12:15
PHST- 2021/10/29 00:00 [received]
PHST- 2022/01/21 00:00 [revised]
PHST- 2022/04/05 06:00 [pubmed]
PHST- 2022/12/02 06:00 [medline]
PHST- 2022/04/04 12:15 [entrez]
PHST- 2022/04/04 00:00 [pmc-release]
AID - 6563183 [pii]
AID - keac167 [pii]
AID - 10.1093/rheumatology/keac167 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2022 Nov 28;61(12):4797-4808. doi: 
      10.1093/rheumatology/keac167.