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Ann Rheum Dis doi:10.1136/ard.2006.065615

Clinical response to adalimumab: The relationship with anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis.

  1. G M Bartelds (m.bartelds{at}janvanbreemen.nl)
  1. Jan van Breemen Institute, Netherlands
    1. C A Wijbrandts (c.a.wijbrandts{at}amc.uva.nl)
    1. AMC/University Medical Center, Netherlands
      1. M T Nurmohamed (m.nurmohamed{at}janvanbreemen.nl)
      1. VUMC, Netherlands
        1. S Stapel (s.stapel{at}sanquin.nl)
        1. Sanquin, Netherlands
          1. W F Lems (rewle{at}slz.nl)
          1. vrije universiteit medisch centrum, Netherlands
            1. L Aarden (l.aarden{at}sanquin.nl)
            1. CLB, Netherlands
              1. BAC AC Dijkmans (secr.reumatologie{at}vumc.nl)
              1. Free University Hospital, Netherlands
                1. PP Tak (p.p.tak{at}amc.uva.nl)
                1. AMC Amsterdam, Netherlands
                  1. G J Wolbink (g.wolbink{at}janvanbreemen.nl)
                  1. Jan van Breemen Institute, Netherlands
                    • Published Online First 14 February 2007

                    Abstract

                    Background: A substantial proportion of rheumatoid arthritis (RA) patients does not respond or loses initial response to adalimumab therapy. One of the explanations for non-response could be that patients develop anti-adalimumab antibodies. Therefore, we evaluated the incidence of antibody formation against adalimumab and the association with serum adalimumab concentrations and clinical response.

                    Methods: In a cohort of 121 consecutive RA patients treated with adalimumab we measured serum adalimumab concentrations and antibodies against adalimumab together with clinical response parameters before and up to 28 weeks after the start of adalimumab treatment.

                    Results: Anti–adalimumab antibodies were detected in 21 patients (17%) during 28 weeks of treatment. EULAR non-responders significantly more often had anti- adalimumab antibodies than good responders (34% vs. 5%), (P = 0.032). Patients with anti-adalimumab antibodies had less improvement in DAS28 score (mean ± SD, delta DAS28: 0.65 ± 1.35) than patients without anti- adalimumab antibodies (mean delta DAS28: 1.70 ± 1.35), (P = 0.001). Patients with anti-adalimumab antibodies during follow-up had lower serum adalimumab concentrations at 28 weeks than patients without anti- adalimumab antibodies (median 1.2 mg/L , range 0.0 - 5.6 vs. median 11.0 mg/L, range 2.0 - 33.0, respectively), (P < 0.001). Good responders had higher serum adalimumab concentrations than moderate (P = 0.021) and non- responders (P = 0.001). Concomitant methotrexate use was lower in the group with anti-adalimumab antibodies (52%) than in the patient group without antibodies (84%), (P = 0.003).

                    Conclusions: Serum antibodies against adalimumab are associated with lower serum adalimumab concentrations and non-response to adalimumab therapy.