Michael Zisapel1, Devy Zisman1, Noa Madar-Balakirski1, Uri Arad1, Hagit Padova1, Hagit Matz1, Hagit Maman-Sarvagyl1, Ilana Kaufman1, Daphna Paran1, Joy Feld1, Ira Litinsky1, Irena Wigler1, Dan Caspi1, Ori Elkayam2. 1. From the Department of Rheumatology and Department of Dermatology, Tel Aviv Medical Center; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; Rheumatology Unit, Carmel Medical Center, Haifa, Israel.M. Zisapel, MD; N. Madar-Balakirski, PhD; U. Arad, MD, PhD; H. Padova, MD; H. Maman-Sarvagyl, MD; I. Kaufman, MD; D. Paran, MD; I. Litinsky, MD; I. Wigler, MD; D. Caspi, MD; O. Elkayam, MD, Department of Rheumatology, Tel Aviv Medical Center, and the Sackler Faculty of Medicine, Tel Aviv University; D. Zisman, MD; J. Feld, MD, Rheumatology Unit, Carmel Medical Center; H. Matz, MD, Department of Dermatology, Tel Aviv Medical Center. 2. From the Department of Rheumatology and Department of Dermatology, Tel Aviv Medical Center; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; Rheumatology Unit, Carmel Medical Center, Haifa, Israel.M. Zisapel, MD; N. Madar-Balakirski, PhD; U. Arad, MD, PhD; H. Padova, MD; H. Maman-Sarvagyl, MD; I. Kaufman, MD; D. Paran, MD; I. Litinsky, MD; I. Wigler, MD; D. Caspi, MD; O. Elkayam, MD, Department of Rheumatology, Tel Aviv Medical Center, and the Sackler Faculty of Medicine, Tel Aviv University; D. Zisman, MD; J. Feld, MD, Rheumatology Unit, Carmel Medical Center; H. Matz, MD, Department of Dermatology, Tel Aviv Medical Center. oribe14@netvision.net.il.
Abstract
OBJECTIVE: The longterm use of tumor necrosis factor (TNF)-α blockers is limited by the formation of neutralizing antibodies. To the best of our knowledge, immunogenicity in psoriatic arthritis (PsA) has not been investigated in depth. Our objective was to evaluate the prevalence and significance of TNF-α blocker immunogenicity in PsA. METHODS: Consecutive patients with PsA treated with either infliximab (IFX), adalimumab (ADA), or etanercept (ETN) > 3 months participated in our cross-sectional study. Their demographic and clinical characteristics, skin and joint disease activity, and records of use of methotrexate (MTX) and other medications were collected. Drug levels (ELISA) and antidrug antibodies (ADAb; Bridging ELISA) were evaluated before the next injection or infusion. RESULTS: A total of 93 patients with PsA were recruited (48 receiving ADA, 24 IFX, and 21 ETN), with a mean age of 53 years (range 21-83 yrs), composed of 53% women. One-fourth of the patients were concomitantly treated with MTX. Altogether, 77% of the patients demonstrated therapeutic drug levels. High levels of ADAb were found in 29% of patients taking ADA, 21% taking IFX, and 0% taking ETN. ADAb significantly correlated with lower drug levels, higher 28-joint Disease Activity Scores, and higher global assessments. MTX use correlated significantly with a lower prevalence of ADAb. CONCLUSION: Significant levels of ADAb were present in up to 29% of patients with PsA treated with ADA or IFX. ADAb clearly correlated with low therapeutic drug levels and higher disease activity variables. The use of MTX significantly decreased ADAb prevalence, and its use should be strongly considered in combination with TNF-α blocker antibodies in patients with PsA.
OBJECTIVE: The longterm use of tumor necrosis factor (TNF)-α blockers is limited by the formation of neutralizing antibodies. To the best of our knowledge, immunogenicity in psoriatic arthritis (PsA) has not been investigated in depth. Our objective was to evaluate the prevalence and significance of TNF-α blocker immunogenicity in PsA. METHODS: Consecutive patients with PsA treated with either infliximab (IFX), adalimumab (ADA), or etanercept (ETN) > 3 months participated in our cross-sectional study. Their demographic and clinical characteristics, skin and joint disease activity, and records of use of methotrexate (MTX) and other medications were collected. Drug levels (ELISA) and antidrug antibodies (ADAb; Bridging ELISA) were evaluated before the next injection or infusion. RESULTS: A total of 93 patients with PsA were recruited (48 receiving ADA, 24 IFX, and 21 ETN), with a mean age of 53 years (range 21-83 yrs), composed of 53% women. One-fourth of the patients were concomitantly treated with MTX. Altogether, 77% of the patients demonstrated therapeutic drug levels. High levels of ADAb were found in 29% of patients taking ADA, 21% taking IFX, and 0% taking ETN. ADAb significantly correlated with lower drug levels, higher 28-joint Disease Activity Scores, and higher global assessments. MTX use correlated significantly with a lower prevalence of ADAb. CONCLUSION: Significant levels of ADAb were present in up to 29% of patients with PsA treated with ADA or IFX. ADAb clearly correlated with low therapeutic drug levels and higher disease activity variables. The use of MTX significantly decreased ADAb prevalence, and its use should be strongly considered in combination with TNF-α blocker antibodies in patients with PsA.
Authors: Gustavo Deza; Jaime Notario; Marta Ferran; Emma Beltrán; Miriam Almirall; Rebeca Alcalá; José Carlos Ruiz-Carrascosa; Ricardo Sánchez; Silvia Pérez; María Luz García-Vivar; Eva Galíndez; Maribel Mora; Jesús Rodríguez; Fernando Gallardo Journal: Rheumatol Int Date: 2018-08-24 Impact factor: 2.631
Authors: Peter Nash; Iain B McInnes; Philip J Mease; Howard Thom; Matthias Hunger; Andreas Karabis; Kunal Gandhi; Shephard Mpofu; Steffen M Jugl Journal: Rheumatol Ther Date: 2018-03-31