Background: Patients with polyarticular-course juvenile idiopathic arthritis (pJIA), receiving disease-modifying anti-rheumatic drugs with immunosuppressive effects, may be at increased risk of vaccine-preventable infections. This substudy assessed protective antibody responses to diphtheria and tetanus vaccination given prior to study enrolment in patients with pJIA.
Findings: This was a substudy of a 24-month, single-arm, open-label, multicenter, Phase III trial (NCT01844518) of subcutaneous abatacept in children with active pJIA (N = 219). Patients aged 2-5 years, with ≥2 continuous months of weekly weight-tiered (10-< 25 kg [50 mg], 25-< 50 kg [87.5 mg]) subcutaneous abatacept treatment (with/without methotrexate and/or low-dose corticosteroids), who received diphtheria/tetanus vaccine prior to enrolment, were eligible. Protective antibody levels to diphtheria/tetanus (> 0.1 IU/mL), and safety, were assessed. Overall, 29 patients were analyzed: 19 (65.5%), 1 (3.4%) and 9 (31.0%) patients had > 12, 6-12 and 2-< 6 months of abatacept exposure, respectively. All patients had protective antibody levels to tetanus and 26 (89.7%) patients had protective antibody levels to diphtheria. Of the 3 patients without protective antibody levels to diphtheria, each had an antibody level of 0.1 IU/mL, bordering the lower threshold of protection. Concomitant use of methotrexate and/or low-dose corticosteroids had no evident effect on antibody levels. No unexpected adverse events, including cases of diphtheria or tetanus, were reported during the 24-month period.
Conclusions: Patients aged 2-5 years with pJIA who received 2-24 months of weekly subcutaneous abatacept, with or without concomitant methotrexate and/or low-dose corticosteroids, maintained effective diphtheria and tetanus vaccination protection without new safety signals.
Trial registration: ClinicalTrials.gov (NCT01844518); registered May 1, 2013; https://clinicaltrials.gov/ct2/show/NCT01844518?term=NCT01844518&rank=1.
Keywords: Abatacept; Biologic DMARDs; Juvenile idiopathic arthritis; Vaccination.
Conflict of interest statement
HIB: speakers’ bureaus: Genentech, GlaxoSmithKline and Novartis; Cincinnati Children’s Hospital Medical Center has received consulting fees from AbbVie, AstraZeneca, Bristol-Myers Squibb, Centocor, Eli Lilly, Genentech, Hoffmann-La Roche, Novartis, Pfizer, Regeneron, UBC and Xoma and for the work of HIB. NT: No conflicts to declare. GVC: consulting fees: AbbVie, Bayer, Bristol-Myers Squibb, Janssen, Sanofi and UCB. RJ: No conflicts to declare. EG: speaking fees: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer and Roche. RCi: consulting fees or speakers’ bureau: AbbVie, Novartis, Sanofi, Sobi. ICP: speaking fees: AbbVie, Novartis, Roche and Sobi; research support: Novartis. RCu: Principal Investigator, medical advisor, speaker: AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche and Sanofi Aventis. TL: No conflicts to declare. PQ: consulting fees: AbbVie, Bristol-Myers Squibb, Lilly, Novartis, Novimmune, Pfizer, Roche and Sobi; speakers’ bureau: AbbVie, Bristol-Myers Squibb, MedImmune, Novartis, Pfizer, Roche and Sobi; safety monitoring board: Sanofi; trial investigator: AbbVie, Bristol-Myers Squibb, Lilly, Novartis, Pfizer, Roche and Sanofi; congress financial support: AbbVie, Bristol-Myers Squibb, Novartis, Pfizer and Sobi. YG, MN and RW: employees and shareholders: Bristol-Myers Squibb. AM: During the last 3 years AM did not have any conflict of interest to declare because starting March 1, 2016, he’d been the Scientific Director of the Giannina Gaslini Hospital, and this role did not allow him to render private consultancies resulting in personal income. Prior to this, AM was a consultant for AbbVie, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, Pfizer and R-Pharm. The money received for these activities was directly transferred to the Gaslini Institute’s bank account. Since January 2019, AM is no longer the Scientific Director of Istituto Gaslini; therefore, he can perform private consultancy services. Currently he has active consultancy agreements with Janssen, Novartis and Pfizer. DJL: speakers’ bureau: Bristol-Myers Squibb and Genentech; Data and Safety Monitoring Board: Forest Research and the National Institutes of Health-NIAMS; Cincinnati Children’s Hospital Medical Center has received consulting fees from AbbVie, AstraZeneca, Bristol-Myers Squibb, Centocor, Genentech, Hoffmann-La Roche, Novartis, Pfizer, Regeneron, UBC and Xoma for the work of DJL. NR: honoraria for consultancy or speakers’ bureaus: AbbVie, Ablynx, AstraZeneca, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffman-La Roche, Janssen, Novartis, Pfizer, R-Pharm, Sanofi, Sinergie, Sobi and Takeda. The Gaslini Hospital has received contributions from the following companies: Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi. This money has been reinvested for the research activities of the hospital in a fully independent manner besides any commitment with third parties.
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