PMID- 29982913
OWN - NLM
STAT- MEDLINE
DCOM- 20190701
LR  - 20190701
IS  - 1434-9949 (Electronic)
IS  - 0770-3198 (Linking)
VI  - 37
IP  - 12
DP  - 2018 Dec
TI  - Development and effect of antibodies to anakinra during treatment of severe CAPS: 
      sub-analysis of a long-term safety and efficacy study.
PG  - 3381-3386
LID - 10.1007/s10067-018-4196-x [doi]
AB  - Anakinra is an effective, well-tolerated, long-term anti-inflammatory treatment 
      for cryopyrin-associated periodic syndromes (CAPS), yet evidence shows that it 
      can induce the development of anti-drug antibodies (ADA). This analysis aims to 
      determine ADA occurrence in CAPS patients and elucidate their effects on anakinra 
      dosing and drug efficacy. A post hoc analysis was performed on data from a 
      long-term safety and efficacy study in patients with severe CAPS. Patients were 
      initiated on an anakinra dose of 1.0-2.4 mg/kg once daily subcutaneously, which 
      was increased (in 0.5-1.0 mg/kg increments) to 2.0-5.0 mg/kg/day according to 
      clinical need (median 3.1 mg/kg/day). ADA, serum amyloid A (SAA), and C-reactive 
      protein (CRP) levels were measured at various time points, and pharmacokinetic 
      (PK) parameters at 1 and 3 months. Efficacy was evaluated using a diary symptom 
      sum score (DSSS), and SAA and CRP levels were evaluated as proxies of efficacy. 
      Safety was evaluated by an analysis of adverse events (AEs). Anakinra dose levels 
      were unrelated to ADA status. A high proportion of patients with at least one 
      post-baseline assessment developed ADA (83%), the majority (79%) within 3 months. 
      However, anakinra treatment markedly improved symptoms and was effective 
      regardless of the presence of ADA; the annual rates of AEs were comparable 
      between ADA-negative and ADA-positive patients. While ADA are likely to occur in 
      CAPS patients treated with anakinra, our evidence shows that chronic daily 
      subcutaneous treatment with anakinra is safe and effective regardless of the 
      development and presence of ADA.
FAU - Wiken, Margareta
AU  - Wiken M
AUID- ORCID: 0000-0001-7900-4765
AD  - Swedish Orphan Biovitrum AB (publ), Stockholm, Sweden. Margareta.Wiken@sobi.com.
FAU - Hallen, Bengt
AU  - Hallen B
AD  - Swedish Orphan Biovitrum AB (publ), Stockholm, Sweden.
FAU - Kullenberg, Torbjorn
AU  - Kullenberg T
AD  - Swedish Orphan Biovitrum AB (publ), Stockholm, Sweden.
FAU - Koskinen, Lisa Osterling
AU  - Koskinen LO
AD  - Swedish Orphan Biovitrum AB (publ), Stockholm, Sweden.
LA  - eng
GR  - N/A/Swedish Orphan Biovitrum AB (publ)/
PT  - Journal Article
DEP - 20180707
PL  - Germany
TA  - Clin Rheumatol
JT  - Clinical rheumatology
JID - 8211469
RN  - 0 (Antibodies)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies/*immunology
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Antirheumatic Agents/therapeutic use
MH  - Area Under Curve
MH  - Biomarkers/metabolism
MH  - Body Weight
MH  - Child
MH  - Child, Preschool
MH  - Cryopyrin-Associated Periodic Syndromes/immunology/*therapy
MH  - Female
MH  - Humans
MH  - Infant
MH  - Inflammation
MH  - Interleukin 1 Receptor Antagonist Protein/immunology/*pharmacology
MH  - Male
MH  - Middle Aged
MH  - Patient Safety
MH  - Prospective Studies
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - Anakinra
OT  - Anti-drug antibody (ADA)
OT  - Cryopyrin-associated periodic syndromes (CAPS)
OT  - Dosing
OT  - Neonatal-onset multisystem inflammatory disease (NOMID)
OT  - Pharmacokinetics (PK)
EDAT- 2018/07/10 06:00
MHDA- 2019/07/02 06:00
CRDT- 2018/07/09 06:00
PHST- 2018/04/19 00:00 [received]
PHST- 2018/06/28 00:00 [accepted]
PHST- 2018/06/26 00:00 [revised]
PHST- 2018/07/10 06:00 [pubmed]
PHST- 2019/07/02 06:00 [medline]
PHST- 2018/07/09 06:00 [entrez]
AID - 10.1007/s10067-018-4196-x [pii]
AID - 10.1007/s10067-018-4196-x [doi]
PST - ppublish
SO  - Clin Rheumatol. 2018 Dec;37(12):3381-3386. doi: 10.1007/s10067-018-4196-x. Epub 
      2018 Jul 7.