Cytokine profiles during infliximab monotherapy in psoriatic arthritis.
BACKGROUND
Biological therapies are a new breakthrough in the treatment of psoriasis and psoriatic arthritis (PsA). Among these, tumour necrosis factor (TNF)-alpha 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.


OBJECTIVE
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-alpha 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-alpha, 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-alpha 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-alpha 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-alpha serum levels in the initial phases. Apoptosis may play an important role in the modulation of the inflammatory response.
Mastroianni
A
A
Clinical Dermatology, San Gallicano Dermatological Institute, Via Chianesi 53, Rome, Italy.
Minutilli
E
E
Mussi
A
A
Bordignon
V
V
Trento
E
E
D'Agosto
G
G
Cordiali-Fei
P
P
Berardesca
E
E
D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D004334:Drug Administration Schedule; D019040:E-Selectin / Q000097:blood; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000069285:Infliximab; D015850:Interleukin-6 / Q000097:blood; D007596:Joints / Q000000981:diagnostic imaging; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D012867:Skin / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000911:Antibodies, Monoclonal; D016207:Cytokines; D019040:E-Selectin; D007155:Immunologic Factors; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D000069285:Infliximab; D020778:Matrix Metalloproteinase 2