PMID- 35508288
OWN - NLM
STAT- MEDLINE
DCOM- 20220707
LR  - 20220823
IS  - 1778-7254 (Electronic)
IS  - 1297-319X (Linking)
VI  - 89
IP  - 4
DP  - 2022 Jul
TI  - Rheumatic immune-and nonimmune-related adverse events in phase 3 clinical trials 
      assessing PD-(L)1 checkpoint inhibitors for lung cancer: A systematic review and 
      meta-analysis.
PG  - 105403
LID - S1297-319X(22)00062-8 [pii]
LID - 10.1016/j.jbspin.2022.105403 [doi]
AB  - OBJECTIVES: We aimed to analyze rheumatic immune-related (ir) and 
      nonimmune-related adverse events (AEs) due to immune-checkpoint inhibitors (ICIs) 
      targeting programmed cell death-1 or its ligand PD-(L)1 in lung cancer patients 
      from the available literature. METHODS: We performed a systematic review and 
      meta-analysis of phase III randomized clinical trials (RCTs) assessing 
      PD-(L)1-ICIs in lung cancer patients, from inception until January 12th, 2021. We 
      extracted data of each trial to estimate odds ratio (OR) for rheumatic ir or 
      non-irAE as classified in RCTs safety data. Sensitivity analyses (by ICI, 
      treatment group and histology) were performed. RESULTS: Eighteen RCTs met the 
      inclusion criteria (n=12172 subjects). The OR [95%IC] for rheumatic irAE in ICIs 
      versus controls (either placebo or chemotherapy) was 2.20 [0.85,5.72]. Among 
      rheumatic non-irAEs, both overall and severe (grade>/=3) back pain were 
      significantly more frequent in ICIs versus controls, 2.01 [1.09;3.73] and 2.90 
      [1.18;7.08], respectively. The overall frequency of arthralgia was similar 
      between ICIs and controls; by sensitivity analysis RCTs assessing ICIs in 
      combination with chemotherapy showed a significant association with arthralgia 
      (1.55 [1.15;2.10]). Similarly, the frequency of myalgia was significantly lower 
      in RCTs assessing ICIs alone versus chemotherapy (OR 0.32 [0.24;0.42]). Muscular 
      pain was not significantly increased with ICI. CONCLUSION: Rheumatic irAEs are 
      not increased in RCTs assessing PD-(L)1 inhibitors, not reflecting the real-life 
      incidence, therefore likely underreported or misclassified. Back pain is 
      significantly associated with them regardless its severity, while arthralgia only 
      when ICIs are added on conventional chemotherapy.
CI  - Copyright (c) 2022 Societe francaise de rhumatologie. Published by Elsevier Masson 
      SAS. All rights reserved.
FAU - Veccia, Antonello
AU  - Veccia A
AD  - Medical Oncology, Santa Chiara Hospital, APSS Trento, Italy.
FAU - Kostine, Marie
AU  - Kostine M
AD  - Rheumatology Department, CHU Bordeaux, 33000 Bordeaux, France.
FAU - Tison, Alice
AU  - Tison A
AD  - Rheumatologie, CHU de Brest, Universite de Bretagne Occidentale, INSERM, 1227 
      Brest, France.
FAU - Dipasquale, Mariachiara
AU  - Dipasquale M
AD  - Medical Oncology, Santa Chiara Hospital, APSS Trento, Italy.
FAU - Kinspergher, Stefania
AU  - Kinspergher S
AD  - Medical Oncology, Santa Chiara Hospital, APSS Trento, Italy.
FAU - Prokop, Larry
AU  - Prokop L
AD  - Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA.
FAU - Grandi, Guido
AU  - Grandi G
AD  - Laboratory of Synthetic and Structural Vaccinology (SSV), Department of CIBIO; 
      University of Trento, Italy.
FAU - Inchiostro, Sandro
AU  - Inchiostro S
AD  - Internal Medicine, San Lorenzo Hospital, Borgo Valsugana, APSS Trento, Italy.
FAU - Caffo, Orazio
AU  - Caffo O
AD  - Medical Oncology, Santa Chiara Hospital, APSS Trento, Italy.
FAU - Paolazzi, Giuseppe
AU  - Paolazzi G
AD  - Internal Medicine, San Lorenzo Hospital, Borgo Valsugana, APSS Trento, Italy; 
      Department of Rheumatology, San Camillo Hospital, Trento, Italy.
FAU - Bortolotti, Roberto
AU  - Bortolotti R
AD  - Department of Rheumatology, Santa Chiara Hospital, APSS Trento, Italy.
FAU - Cornec, Divi
AU  - Cornec D
AD  - Rheumatologie, CHU de Brest, Universite de Bretagne Occidentale, INSERM, 1227 
      Brest, France; Thoracic Disease Research Unit, Mayo Clinic, Rochester, MN, USA. 
      Electronic address: divi.cornec@chu-brest.fr.
FAU - Berti, Alvise
AU  - Berti A
AD  - Laboratory of Synthetic and Structural Vaccinology (SSV), Department of CIBIO; 
      University of Trento, Italy; Department of Rheumatology, Santa Chiara Hospital, 
      APSS Trento, Italy; Thoracic Disease Research Unit, Mayo Clinic, Rochester, MN, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20220501
PL  - France
TA  - Joint Bone Spine
JT  - Joint bone spine
JID - 100938016
RN  - 0 (Antineoplastic Agents, Immunological)
SB  - IM
MH  - *Antineoplastic Agents, Immunological/adverse effects
MH  - Arthralgia/chemically induced
MH  - Humans
MH  - *Lung Neoplasms/drug therapy/pathology
OTO - NOTNLM
OT  - Arthralgia
OT  - Immune checkpoint inhibitors
OT  - Immune related adverse event
OT  - Lung cancer
OT  - Meta-analysis
OT  - Randomized clinical trials
OT  - Rheumatic adverse events
EDAT- 2022/05/05 06:00
MHDA- 2022/07/08 06:00
CRDT- 2022/05/04 19:24
PHST- 2021/09/18 00:00 [received]
PHST- 2022/03/25 00:00 [revised]
PHST- 2022/03/30 00:00 [accepted]
PHST- 2022/05/05 06:00 [pubmed]
PHST- 2022/07/08 06:00 [medline]
PHST- 2022/05/04 19:24 [entrez]
AID - S1297-319X(22)00062-8 [pii]
AID - 10.1016/j.jbspin.2022.105403 [doi]
PST - ppublish
SO  - Joint Bone Spine. 2022 Jul;89(4):105403. doi: 10.1016/j.jbspin.2022.105403. Epub 
      2022 May 1.