Elsevier

Joint Bone Spine

Volume 79, Issue 1, January 2012, Pages 85-87
Joint Bone Spine

Case report
Psoriatic arthritis in two patients with an inadequate response to treatment with tocilizumab

https://doi.org/10.1016/j.jbspin.2011.06.011Get rights and content

Abstract

Psoriatic arthritis (PsA) is considered as one of the seronegative spondylarthropathies. Like rheumatoid arthritis (RA), the increased production of interleukin (IL)-6 suggests a pathogenic role of IL-6 in PsA. However, whether humanized anti-IL-6 receptor antibody such as tocilizumab (TCZ) might be effective for PsA as well as RA has yet to be determined. We report herein two cases of PsA treated using TCZ. Although, TCZ treatment resulted in disappearance of serum CRP in both patients, arthritis and skin lesions were not improved despite 6-month administration of TCZ. In contrast, tumor necrosis factor (TNF) inhibitor proved effective against arthritis and skin lesions in these patients. Collectively, these findings not only indicate that IL-6 has distinct pathological roles in RA and PsA, but also suggest that TNF inhibitor therapy (but not TCZ) is effective for arthritis and skin lesions of PsA.

Introduction

Psoriatic arthritis (PsA) is a common inflammatory arthritis that is associated with psoriasis. Like rheumatoid arthritis (RA), increased production of interleukin (IL)-6 is well known in psoriasis and PsA [1], [2].

Most reports have demonstrated correlations between serum levels of IL-6 and disease severity of PsA [3], mouse with epidermal over expression of IL-6 (K14-IL-6 transgenic mouse) exhibits phenotype of psoriasis [4]. The transcription factor signal transducer and activator of transcription 3 (STAT3) is up regulated in psoriasis and IL-6 induces STAT3 phosphorylation and are also thought to be potential therapeutic targets [5].

Characteristic features differ between PsA and RA. In PsA, peripheral arthritis evolves with a distinct joint pattern, potentially involving the distal interphalangeal joints. Dactylitis with enthesitis involving the entire digit is a characteristic feature. Furthermore, articular damage as assessed by radiographic erosion is more common than in RA and typically shows an asymmetric pattern in PsA. Despite these differences in characteristic features, therapeutic options including tumor necrosis factor (TNF) inhibitors and methods of assessing disease activity are mostly held in common. This suggests that IL-6 may play a similar role in the inflammatory arthritis in both RA and PsA.

A humanized anti-IL-6 receptor antibody, tocilizumab (TCZ), was recently approved for RA patients and efficacy of TCZ in patients with RA has been demonstrated [6]. PsA is included in the category of seronegative spondylarthritides, which are defined by the absence of rheumatoid factor and include diseases such as ankylosing spondylitis (AS) and reactive arthritis (ReA). Variable efficacy of TCZ has also been reported in patients with ReA [7] and AS [8], [9], [10], since the efficacy is variable pending of the evaluation. However, whether TCZ is effective for PsA as well as RA has not been determined. We therefore tried using TCZ in patients with PsA. Severity of inflammation was evaluated using erythrocyte sedimentation rate (ESR), and levels of C-reactive protein (CRP) and matrix metalloproteinase (MMP)-3. Severity of arthritis was evaluated by two measures of composite disease activity: Disease Activity Score including the 28-joint count (DAS28) and Clinical Disease Activity Index (CDAI). Severity of psoriatic skin was evaluated using the Psoriasis Area-and-Severity Index (PASI).

Section snippets

Case 1

A 35-year-old man was diagnosed with psoriasis in July 2002 and developed complications of arthritis in April 2004, particularly in bilateral knee and shoulder joints. Since prednisolone (5 mg/day) and cyclosporine (5 mg/kg/day) proved ineffective for improving arthritis, methotrexate was started at 6 mg/week, then the anti-TNF antibody Infliximab (IFX) was started at 3 mg/kg in November 2006. Although, arthritis and eruptions initially showed marked improvements, symptoms exacerbated in June 2008.

Case 2

A 28-year-old man was diagnosed with psoriasis in 1991 and developed complications with arthritis in 2002. Since response to DMARDs (disease-modifying antirheumatic drugs) including sulfasalazopiridine (1000 mg/day) and methotrexate (6 mg/week) was inadequate, he joined the Japanese phase III study of ADA in 2006. Arthritis and eruptions were significantly improved during ADA treatment. However, symptoms showed flare-up after the 1-year ADA therapy. In September 2008, he joined a Japanese phase

Discussion

Although, the characteristics of arthritis differ between PsA and RA, most therapeutic options for these diseases are similar. The differences in mechanism of arthritis between RA and PsA are thus unclear. We report herein the inadequate response to TCZ in PsA, suggesting a different pathogenic role of IL-6 in RA and PsA. In our patients, TCZ normalized CRP levels. Since CRP is induced by IL-6, we can monitor the efficacy of TCZ in suppressing IL-6 by monitoring CRP. IL-6 function thus appeared

Disclosure of interest

AO received consultant fee from Chugai Pharmaceutical Co. Ltd.

NU, IK. AK and TT have no conflict interest.
Funding: This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences from the National Institute of Biomedical Innovation.

References (15)

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