Cytokine profiles during infliximab monotherapy in psoriatic arthritis

A. Mastroianni, E. Minutilli, A. Mussi, V. Bordignon, E. Trento, G. D'Agosto, P. Cordiali-Fei, Enzo Berardesca

Research output: Contribution to journalArticle

Abstract

Background: Biological therapies are a new breakthrough in the treatment of psoriasis and psoriatic arthritis (PsA). Among these, tumour necrosis factor (TNF)-α antagonists such as infliximab and etanercept are the most promising as TNF is considered to be essential in driving cytokine cascade at sites of cutaneous and synovial inflammation in this disease. Objectives: To evaluate the time-related response of serum cytokine release during infliximab monotherapy and assess serum cytokine levels in order to provide a fast, minimally invasive tool to monitor and/or predict efficacy of anti-TNF-α therapy. Methods: Twenty patients affected by PsA with Psoriasis Area and Severity Index (PASI) score between 0.4 and 42.8 were treated with infliximab for 30-42 weeks. The assessment of arthritis severity was performed using the American College of Rheumatology (ACR) criteria and ultrasonography evaluation. The treatment schedule consisted of infliximab (5 mg kg-1 intravenously) at 0, 2 and 6 weeks and every 12 weeks on an individual basis determined by therapeutic results and adverse events reported. At baseline and before every infusion blood samples were taken to assess serum cytokine levels [TNF-α, interleukin (IL-6), E-selectin, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF), matrix metalloproteinase (MMP-2)]. Results: Eighteen of 20 psoriatic patients achieved > 50% improvement and 14 of 20 patients attained > 75% improvement in the PASI score at 10 weeks. All arthritic patients achieved > 50% improvement (ACR-50) and 16 of 20 patients attained > 75% improvement (ACR-75) at 10 weeks. TNF-α did not decrease immediately during the first part of the study. A significant decrease was detected at week 12 (P <0.01). In contrast, IL-6, VEGF, FGF and E-selectin showed significant decreases after early infliximab infusions. PASI was not correlated with TNF-α in the serum but was significantly correlated with FGF, VEGF and MMP-2. Treatment was well tolerated and there were no significant adverse events in most patients, other than an urticarial reaction and an autoimmune hepatitis. Conclusions: Monotherapy with infliximab has to be considered an efficacious and safe treatment for PsA in comparison with traditional disease-modifying antirheumatic drugs. The resolution of cutaneous and synovial symptoms is not related to TNF-α serum levels in the initial phases. Apoptosis may play an important role in the modulation of the inflammatory response.

Original languageEnglish
Pages (from-to)531-536
Number of pages6
JournalBritish Journal of Dermatology
Volume153
Issue number3
DOIs
Publication statusPublished - Sep 2005

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Psoriatic Arthritis
Tumor Necrosis Factor-alpha
Cytokines
Psoriasis
Fibroblast Growth Factors
Vascular Endothelial Growth Factor A
Interleukin-6
Serum
E-Selectin
Rheumatology
Matrix Metalloproteinases
Arthritis
Therapeutics
Autoimmune Hepatitis
Skin
Biological Therapy
Antirheumatic Agents
Matrix Metalloproteinase 2
Infliximab
Ultrasonography

Keywords

  • Cytokines
  • Infliximab
  • Interleukin-6
  • Matrix metalloproteinase-2
  • Psoriasis
  • Tumour necrosis factor-alpha

ASJC Scopus subject areas

  • Dermatology

Cite this

Cytokine profiles during infliximab monotherapy in psoriatic arthritis. / Mastroianni, A.; Minutilli, E.; Mussi, A.; Bordignon, V.; Trento, E.; D'Agosto, G.; Cordiali-Fei, P.; Berardesca, Enzo.

In: British Journal of Dermatology, Vol. 153, No. 3, 09.2005, p. 531-536.

Research output: Contribution to journalArticle

Mastroianni, A. ; Minutilli, E. ; Mussi, A. ; Bordignon, V. ; Trento, E. ; D'Agosto, G. ; Cordiali-Fei, P. ; Berardesca, Enzo. / Cytokine profiles during infliximab monotherapy in psoriatic arthritis. In: British Journal of Dermatology. 2005 ; Vol. 153, No. 3. pp. 531-536.
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abstract = "Background: Biological therapies are a new breakthrough in the treatment of psoriasis and psoriatic arthritis (PsA). Among these, tumour necrosis factor (TNF)-α antagonists such as infliximab and etanercept are the most promising as TNF is considered to be essential in driving cytokine cascade at sites of cutaneous and synovial inflammation in this disease. Objectives: To evaluate the time-related response of serum cytokine release during infliximab monotherapy and assess serum cytokine levels in order to provide a fast, minimally invasive tool to monitor and/or predict efficacy of anti-TNF-α therapy. Methods: Twenty patients affected by PsA with Psoriasis Area and Severity Index (PASI) score between 0.4 and 42.8 were treated with infliximab for 30-42 weeks. The assessment of arthritis severity was performed using the American College of Rheumatology (ACR) criteria and ultrasonography evaluation. The treatment schedule consisted of infliximab (5 mg kg-1 intravenously) at 0, 2 and 6 weeks and every 12 weeks on an individual basis determined by therapeutic results and adverse events reported. At baseline and before every infusion blood samples were taken to assess serum cytokine levels [TNF-α, interleukin (IL-6), E-selectin, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF), matrix metalloproteinase (MMP-2)]. Results: Eighteen of 20 psoriatic patients achieved > 50{\%} improvement and 14 of 20 patients attained > 75{\%} improvement in the PASI score at 10 weeks. All arthritic patients achieved > 50{\%} improvement (ACR-50) and 16 of 20 patients attained > 75{\%} improvement (ACR-75) at 10 weeks. TNF-α did not decrease immediately during the first part of the study. A significant decrease was detected at week 12 (P <0.01). In contrast, IL-6, VEGF, FGF and E-selectin showed significant decreases after early infliximab infusions. PASI was not correlated with TNF-α in the serum but was significantly correlated with FGF, VEGF and MMP-2. Treatment was well tolerated and there were no significant adverse events in most patients, other than an urticarial reaction and an autoimmune hepatitis. Conclusions: Monotherapy with infliximab has to be considered an efficacious and safe treatment for PsA in comparison with traditional disease-modifying antirheumatic drugs. The resolution of cutaneous and synovial symptoms is not related to TNF-α serum levels in the initial phases. Apoptosis may play an important role in the modulation of the inflammatory response.",
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AU - Mastroianni, A.

AU - Minutilli, E.

AU - Mussi, A.

AU - Bordignon, V.

AU - Trento, E.

AU - D'Agosto, G.

AU - Cordiali-Fei, P.

AU - Berardesca, Enzo

PY - 2005/9

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KW - Infliximab

KW - Interleukin-6

KW - Matrix metalloproteinase-2

KW - Psoriasis

KW - Tumour necrosis factor-alpha

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