Prevalence of TNF-α blocker immunogenicity in psoriatic arthritis.
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.


CONCLUSIONS
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.
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.
Michael
M
Zisapel
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.
Devy
D
Zisman
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.
Noa
N
Madar-Balakirski
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.
Uri
U
Arad
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.
Hagit
H
Padova
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.
Hagit
H
Matz
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.
Hagit
H
Maman-Sarvagyl
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.
Ilana
I
Kaufman
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.
Daphna
D
Paran
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.
Joy
J
Feld
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.
Ira
I
Litinsky
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.
Irena
I
Wigler
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.
Dan
D
Caspi
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.
Ori
O
Elkayam
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000276:immunology*; D018501:Antirheumatic Agents / Q000276:immunology* / Q000627:therapeutic use; D015535:Arthritis, Psoriatic / Q000188:drug therapy / Q000276:immunology*; D003430:Cross-Sectional Studies; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate
ADALIMUMAB; ARTHRITIS; ETANERCEPT; IMMUNOGENICITY; INFLIXIMAB; PSORIATIC