PMID- 32446286
OWN - NLM
STAT- MEDLINE
DCOM- 20210602
LR  - 20210602
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 184
IP  - 3
DP  - 2021 Mar
TI  - Meta-analysis results do not reflect the real safety of biologics in psoriasis.
PG  - 415-424
LID - 10.1111/bjd.19244 [doi]
AB  - BACKGROUND: In reported systematic reviews and meta-analyses of randomized 
      controlled trials (RCTs) assessing treatments for psoriasis, the proportion of 
      serious adverse events (SAEs) did not differ between treatments and placebo. 
      Including cases of psoriasis worsening as SAEs may explain the lack of 
      difference. OBJECTIVES: This systematic review and meta-analysis aimed to explore 
      this possibility. METHODS: Among the 140 RCTs included in the Living Network 
      Cochrane Review (last search on 8 May 2019), we selected those comparing a 
      biologic treatment against placebo. The primary outcome was the numbers of SAEs 
      in the treatment and placebo arms after excluding cases of psoriasis worsening. 
      Secondary outcomes were the number of adverse events (AEs) of special interest. 
      The trial was registered on PROSPERO (CRD42019124495). RESULTS: We analysed 51 
      RCTs. Of these, 21 included at least one anti-tumour necrosis factor (TNF)-alpha arm, 
      15 one anti-interleukin (IL)-17 arm, 11 one anti-IL-23 arm and nine one 
      anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of 
      occurrence of SAEs between biologic treatments and placebo did not differ: risk 
      ratio (RR) 1.09, 95% confidence interval (CI) 0.88-1.36. After excluding cases of 
      psoriasis worsening, the RR became significant (RR 1.30, 95% CI 1.02-1.65). By 
      drug class, the RRs were for anti-TNF-alpha, 1.68 (95% CI 1.11-2.54; no missing 
      data); anti-IL-17, 1.28 (95% CI 0.88-1.85; no missing data); anti-IL-23, 0.95 
      (95% CI 0.59-1.52; no missing data) and anti-IL-12/23, 1.18 (95% CI 0.72-1.94; no 
      missing data). We were unable to examine potential differences in AEs of special 
      interest between biologic treatments and placebo arms because of the small number 
      of events. CONCLUSIONS: On excluding cases of worsening psoriasis, the risk of 
      occurrence of SAEs is higher in the biologic than in the placebo arm. Given the 
      rare events, we could not highlight whether this higher risk of SAEs was related 
      to AEs of special interest. Reporting of SAEs in clinical trials has to be 
      changed to provide more transparency through the separate reporting of disease 
      flares leading to hospital admission and other SAEs.
CI  - (c) 2020 British Association of Dermatologists.
FAU - Afach, S
AU  - Afach S
AUID- ORCID: 0000-0003-2791-223X
AD  - Universite Paris-Est Creteil, UPEC, EpiDermE EA 7379, Creteil, F-94010, France.
FAU - Chaimani, A
AU  - Chaimani A
AUID- ORCID: 0000-0003-2828-6832
AD  - Universite de Paris, Centre de Recherche Epidemiologie et Statistique Sorbonne 
      Paris Cite (CRESS-UMR1153), Inserm, Inra, Paris, F-75004, France.
AD  - Cochrane France, Paris, France.
FAU - Evrenoglou, T
AU  - Evrenoglou T
AD  - Universite de Paris, Centre de Recherche Epidemiologie et Statistique Sorbonne 
      Paris Cite (CRESS-UMR1153), Inserm, Inra, Paris, F-75004, France.
FAU - Penso, L
AU  - Penso L
AD  - Universite Paris-Est Creteil, UPEC, EpiDermE EA 7379, Creteil, F-94010, France.
FAU - Brouste, E
AU  - Brouste E
AD  - Universite Paris-Est Creteil, UPEC, EpiDermE EA 7379, Creteil, F-94010, France.
FAU - Sbidian, E
AU  - Sbidian E
AUID- ORCID: 0000-0002-1267-5270
AD  - Universite Paris-Est Creteil, UPEC, EpiDermE EA 7379, Creteil, F-94010, France.
AD  - AP-HP, Hopitaux Universitaires Henri Mondor, Departement de Dermatologie, UPEC, 
      Creteil, F-94010, France.
AD  - INSERM, Centre d'Investigation Clinique 1430, Creteil, F-94010, France.
FAU - Le Cleach, L
AU  - Le Cleach L
AUID- ORCID: 0000-0003-1385-6839
AD  - Universite Paris-Est Creteil, UPEC, EpiDermE EA 7379, Creteil, F-94010, France.
AD  - AP-HP, Hopitaux Universitaires Henri Mondor, Departement de Dermatologie, UPEC, 
      Creteil, F-94010, France.
LA  - eng
GR  - APHP-180680/Hospital Clinical Research Program/
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20200716
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Biological Products)
RN  - 0 (Interleukin-23)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
CIN - Br J Dermatol. 2021 Mar;184(3):385. PMID: 32880913
MH  - *Biological Products/adverse effects
MH  - Humans
MH  - Interleukin-12
MH  - Interleukin-23
MH  - *Psoriasis/drug therapy
MH  - Tumor Necrosis Factor-alpha
EDAT- 2020/05/24 06:00
MHDA- 2021/06/03 06:00
CRDT- 2020/05/24 06:00
PHST- 2020/05/19 00:00 [accepted]
PHST- 2020/05/24 06:00 [pubmed]
PHST- 2021/06/03 06:00 [medline]
PHST- 2020/05/24 06:00 [entrez]
AID - 10.1111/bjd.19244 [doi]
PST - ppublish
SO  - Br J Dermatol. 2021 Mar;184(3):415-424. doi: 10.1111/bjd.19244. Epub 2020 Jul 16.