PMID- 29867173
OWN - NLM
STAT- MEDLINE
DCOM- 20190806
LR  - 20191210
IS  - 1572-0241 (Electronic)
IS  - 0002-9270 (Linking)
VI  - 113
IP  - 6
DP  - 2018 Jun
TI  - Lymphoma Risk and Overall Safety Profile of Adalimumab in Patients With Crohn's 
      Disease With up to 6 Years of Follow-Up in the Pyramid Registry.
PG  - 872-882
LID - 10.1038/s41395-018-0098-4 [doi]
AB  - OBJECTIVES: Real-world, prospective, long-term studies in Crohn's disease (CD) 
      characterizing adalimumab safety data and lymphoma risk were lacking. We present 
      the final results from the PYRAMID registry, which was designed to rule out a 
      doubling of lymphoma risk in adalimumab-treated patients with CD. METHODS: 
      Patients with moderately to severely active CD newly prescribed or currently 
      receiving adalimumab according to local product labels were followed for up to 6 
      years and analyzed for adverse events (AEs). The registry exposure-adjusted 
      observed rate of lymphoma was compared with the estimated background lymphoma 
      rate from a sex-matched general population in the Surveillance, Epidemiology, and 
      End Results 17 Registry database adjusted for anticipated prior or concurrent 
      thiopurine use in a CD population. RESULTS: A total of 5025 patients were 
      evaluated (16680.4 PY of adalimumab registry exposure,  approximately 3 years/patient mean 
      follow-up). Registry treatment-emergent AEs included 4129 serious AEs (n = 1853 
      [36.9%]; 24.8 E/100 PY), 792 serious infections (n = 556 [11.1%]; 4.7 E/100 PY), 
      and 134 malignancies (n = 116 [2.3%]; 0.8 E/100 PY), including ten lymphomas. The 
      observed lymphoma rate (0.060 E/100 PY) was lower than the estimated background 
      rate (0.084 E/100 PY), and the upper bound of the one-sided 95% CI of the 
      observed rate (0.102 E/100 PY) was lower than double the estimated rate (0.168 
      E/100 PY). CONCLUSIONS: PYRAMID is the longest prospective adalimumab study in 
      routine clinical practice, with up to 6 years of follow-up. No new safety signals 
      were reported. The pre-specified registry objective of ruling out a doubling of 
      lymphoma risk with adalimumab was met.
FAU - D'Haens, Geert
AU  - D'Haens G
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Reinisch, Walter
AU  - Reinisch W
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Panaccione, Remo
AU  - Panaccione R
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Satsangi, Jack
AU  - Satsangi J
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Petersson, Joel
AU  - Petersson J
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Bereswill, Mareike
AU  - Bereswill M
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Arikan, Dilek
AU  - Arikan D
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Perotti, Eva
AU  - Perotti E
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Robinson, Anne M
AU  - Robinson AM
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Kalabic, Jasmina
AU  - Kalabic J
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Alperovich, Gabriela
AU  - Alperovich G
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Thakkar, Roopal
AU  - Thakkar R
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
FAU - Loftus, Edward V
AU  - Loftus EV
AD  - Academic Medical Center, Amsterdam, Netherlands. Medical university of Vienna, 
      Vienna, Austria. Department of Medicine, university of Calgary, Calgary, Canada. 
      Gastrointestinal Unit, Western General Hospital, Edinburgh, UK. AbbVie Inc., 
      North Chicago, IL, USA. AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. 
      AbbVie Spain S.L.U., Madrid, Spain. Mayo Clinic, Division of Gastroenterology and 
      Hepatology, Rochester, NY, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00524537
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20180605
PL  - United States
TA  - Am J Gastroenterol
JT  - The American journal of gastroenterology
JID - 0421030
RN  - 0 (Immunosuppressive Agents)
RN  - FYS6T7F842 (Adalimumab)
MH  - Adalimumab/*adverse effects
MH  - Adult
MH  - Cardiovascular Diseases/epidemiology/immunology
MH  - Crohn Disease/*drug therapy/immunology/mortality
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunosuppressive Agents/*adverse effects
MH  - Infections/epidemiology/immunology
MH  - Injection Site Reaction/epidemiology/immunology
MH  - Lymphoma/*epidemiology/immunology
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Registries/*statistics & numerical data
MH  - Skin Diseases/epidemiology/immunology
MH  - Survival Rate
EDAT- 2018/06/06 06:00
MHDA- 2019/08/07 06:00
CRDT- 2018/06/06 06:00
PHST- 2017/06/02 00:00 [received]
PHST- 2018/04/04 00:00 [accepted]
PHST- 2018/06/06 06:00 [pubmed]
PHST- 2019/08/07 06:00 [medline]
PHST- 2018/06/06 06:00 [entrez]
AID - 10.1038/s41395-018-0098-4 [doi]
PST - ppublish
SO  - Am J Gastroenterol. 2018 Jun;113(6):872-882. doi: 10.1038/s41395-018-0098-4. Epub 
      2018 Jun 5.