PMID- 34498056
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20220716
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Print)
IS  - 1462-0324 (Linking)
VI  - 61
IP  - 6
DP  - 2022 May 30
TI  - Filgotinib or lanraplenib in moderate to severe cutaneous lupus erythematosus: a 
      phase 2, randomized, double-blind, placebo-controlled study.
PG  - 2413-2423
LID - 10.1093/rheumatology/keab685 [doi]
AB  - OBJECTIVES: To explore the safety and efficacy of filgotinib (FIL), a Janus 
      kinase 1 inhibitor, and lanraplenib (LANRA), a spleen kinase inhibitor, in 
      cutaneous lupus erythematosus (CLE). METHODS: This was a phase 2, randomized, 
      double-blind, placebo-controlled, exploratory, proof-of-concept study of LANRA 
      (30 mg), FIL (200 mg) or placebo (PBO) once daily for 12 weeks in patients with 
      active CLE. At week 12, PBO patients were rerandomized 1:1 to receive LANRA or 
      FIL for up to 36 additional weeks. RESULTS: Of 47 randomized patients, 45 were 
      treated (PBO, n = 9; LANRA, n = 19; FIL, n = 17). The primary endpoint [change 
      from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index 
      Activity (CLASI-A) score at week 12] was not met. The least squares mean CLASI-A 
      score change from baseline was -5.5 (s.e. 2.56) with PBO, -4.5 (1.91) with LANRA 
      and -8.7 (1.85) with FIL. Numerical differences between FIL and PBO were greater 
      in select subgroups. A >/=5-point improvement in the CLASI-A score at week 12 was 
      achieved by 50.0%, 56.3% and 68.8% in the PBO, LANRA and FIL arms, respectively. 
      A numerically greater proportion of patients in the FIL arm (50%) also achieved 
      >/=50% improvement in the CLASI-A score at week 12 (37.5% PBO, 31.3% LANRA). Most 
      adverse events (AEs) were mild or moderate in severity. Two serious AEs were 
      reported with LANRA and one with FIL. CONCLUSION: The primary endpoint was not 
      met. Select subgroups displayed a numerically greater treatment response to FIL 
      relative to PBO. LANRA and FIL were generally well tolerated. TRIAL REGISTRATION: 
      ClinicalTrials.gov identifier NCT03134222.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology.
FAU - Werth, Victoria P
AU  - Werth VP
AUID- ORCID: 0000-0003-3030-5369
AD  - Department of Dermatology, Perelman School of Medicine, University of 
      Pennsylvania, Corporal Michael J. Crescenz VAMC, Philadelphia, PA.
FAU - Fleischmann, Roy
AU  - Fleischmann R
AD  - Department of Internal Medicine, Metroplex Clinical Research Center, University 
      of Texas Southwestern Medical Center, Dallas, TX, USA.
FAU - Robern, Michael
AU  - Robern M
AD  - Dermatology Ottawa Research Center, Ottawa.
FAU - Touma, Zahi
AU  - Touma Z
AUID- ORCID: 0000-0001-5177-2076
AD  - Division of Rheumatology, Department of Medicine, Toronto Western Hospital; 
      Institute of Health Policy, Management and Evaluation, University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Tiamiyu, Iyabode
AU  - Tiamiyu I
AD  - Gilead Sciences, Inc., Foster City.
FAU - Gurtovaya, Oksana
AU  - Gurtovaya O
AD  - Gilead Sciences, Inc., Foster City.
FAU - Pechonkina, Alena
AU  - Pechonkina A
AD  - Gilead Sciences, Inc., Foster City.
FAU - Mozaffarian, Afsaneh
AU  - Mozaffarian A
AD  - Gilead Sciences, Inc., Foster City.
FAU - Downie, Bryan
AU  - Downie B
AD  - Gilead Sciences, Inc., Foster City.
FAU - Matzkies, Franziska
AU  - Matzkies F
AD  - Gilead Sciences, Inc., Foster City.
FAU - Wallace, Daniel
AU  - Wallace D
AD  - Rheumatology, Cedars-Sinai/David Geffen School of Medicine at UCLA, Los Angeles, 
      CA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03134222
PT  - Clinical Trial, Phase II
PT  - Journal Article
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  - 0 (Janus Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Triazoles)
SB  - IM
CIN - Rheumatology (Oxford). 2022 May 30;61(6):2213-2214. PMID: 34791095
MH  - Double-Blind Method
MH  - Humans
MH  - *Janus Kinase Inhibitors/adverse effects
MH  - *Lupus Erythematosus, Cutaneous/chemically induced/drug therapy
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Pyridines/adverse effects
MH  - Severity of Illness Index
MH  - Treatment Outcome
MH  - Triazoles/therapeutic use
PMC - PMC9157055
OTO - NOTNLM
OT  - clinical trials and methods
OT  - cytokines and inflammatory mediators
OT  - inflammation
OT  - skin
OT  - systemic lupus erythematosus and autoimmunity
EDAT- 2021/09/10 06:00
MHDA- 2022/06/03 06:00
PMCR- 2021/09/08
CRDT- 2021/09/09 06:56
PHST- 2021/05/07 00:00 [received]
PHST- 2021/09/01 00:00 [revised]
PHST- 2021/09/10 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2021/09/09 06:56 [entrez]
PHST- 2021/09/08 00:00 [pmc-release]
AID - 6366563 [pii]
AID - keab685 [pii]
AID - 10.1093/rheumatology/keab685 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2022 May 30;61(6):2413-2423. doi: 
      10.1093/rheumatology/keab685.