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J Immunol Res. 2015;2015:487230.

Low baseline interleukin-17A levels are associated with better treatment response at 12 weeks to tocilizumab therapy in rheumatoid arthritis patients.

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제1저자 이상진 · 교신저자 송영욱

PMID 25922848 PMC4398953 DOI 10.1155/2015/487230 IF 3.2 류마티스내과
소속 (12)
  1. Division of Rheumatology, Seoul National University Hospital, Seoul, Republic of Korea ; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Medical Research Institute, Seoul National University, Seoul, Republic of Korea.
  2. Division of Rheumatology, Inha University Hospital, Incheon, Republic of Korea.
  3. Division of Rheumatology, The Catholic University of Korea Seoul St. Mary's Hospital, Seoul, Republic of Korea.
  4. Division of Rheumatology, Eulji University Hospital, Daejeon, Republic of Korea.
  5. Division of Rheumatology, Gachon University Gil Medical Center, Incheon, Republic of Korea.
  6. Division of Rheumatology, Hanyang University Medical Center, Seoul, Republic of Korea.
  7. Division of Rheumatology, Hallym University Medical Center, Anyang, Republic of Korea.
  8. Division of Rheumatology, Yonsei University Health System, Seoul, Republic of Korea.
  9. Division of Rheumatology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
  10. Division of Rheumatology, Pusan National University Hospital, Busan, Republic of Korea.
  11. Division of Rheumatology, Samsung Medical Center, Seoul, Republic of Korea.
  12. Division of Rheumatology, Seoul National University Hospital, Seoul, Republic of Korea.

Abstract

T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA) pathogenesis. The study aimed to identify cytokines associated with the treatment response of RA patients to tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin- (IL-) 6 receptor. As an independent substudy of the 24-week, randomized, double-blinded CWP-TCZ301 trial of TCZ in RA patients with an inadequate response to disease-modifying antirheumatic drugs, serum levels of cytokines including tumor necrosis factor-alpha, IL-17A, IL-21, IL-23, IL-6, and soluble IL-6 receptor were measured. Baseline IL-17A levels were significantly lower in RA patients who achieved disease activity score 28 (DAS28) remission at 12 weeks of TCZ treatment, compared to patients not in remission. Patients were stratified into IL-17A low group and IL-17A high group. Significantly more patients in the IL-17A low group achieved remission as compared to the IL-17A high group (47.6 versus 17.4%, P = 0.032). DAS28 improvement was significantly better in the IL-17A low group than in the IL-17A high group at 12 weeks (P = 0.045) and 24 weeks (P = 0.046) after adjustment. Other baseline cytokines were not associated with treatment response to TCZ. The data demonstrate that low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.

Figures

Figure 1
Figure 1 Baseline IL-17A levels are lower in the patients who reached DAS28 ESR remission at 12 weeks of tocilizumab treatment. Baseline serum levels of TNF-α (a), IL-6 (b), sIL-6R (c), IL-21 (e), and IL-23 (f) did not differ between the patients with DAS28 ESR remission (n = 14) and nonremission (n = 30) at 12 weeks of tocilizumab treatment. Only IL-17A levels were significantly lower in the remission patients (d). Of note, sIL-6R levels were not checked in healthy controls. Dot represents each person and bars represent the mean value and SEM. P value was assessed by Mann-WhitneyU test. HC = healthy controls and N/A = not assayed.
Figure 2
Figure 2 Bimodal distribution of IL-17A levels in the patients. Upper normal value of IL-17A level was defined as the mean serum IL-17A levels + 3SD in healthy controls (n = 12). IL-17A levels of RA patients were divided into the IL-17A low (n = 21) and high (n = 23) groups. Vertical line marks the cut-off value (i.e., upper normal value of IL-17A levels in the healthy controls). RA = rheumatoid arthritis; HC = healthy controls.
Figure 3
Figure 3 Low baseline levels of IL-17A are associated with DAS28 ESR remission at 12 weeks of tocilizumab treatment. A significantly higher proportion of patients in the IL-17A low group achieved DAS28 remission at 12 weeks as compared to the IL-17A high group (47.6 versus 17.4%, P = 0.032) by Fisher's exact test (a). Individual DAS28 ESR improved in both groups. However, the improvement in DAS28 ESR was more profound in the IL-17A low group with higher remission rate (b). The improvement in DAS28 ESR was better in the IL-17A low group at 12 weeks (∗ P = 0.045) and 24 weeks (∗∗ P = 0.046) after tocilizumab treatment after adjusting for baseline DAS28 ESR, RF positivity, and levels of TNF-α, IL-21, and IL-23. Data represents mean value ± SEM (c).

그림 출처: PubMed Central 공개 논문 (PMC4398953)

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그 밖의 정보
출판 형태
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
저널
Journal of immunology research · eISSN 2314-7156
전자 출판
2015-04-02
MeSH
Antibodies, Monoclonal, Humanized / therapeutic use · Antirheumatic Agents / therapeutic use · Arthritis, Rheumatoid / diagnosis / drug therapy / metabolism · Cytokines / blood / metabolism · Female · Humans · Interleukin-17 / blood / metabolism · Male · Middle Aged · Time Factors · Treatment Outcome
Substances
Antibodies, Monoclonal, Humanized · Antirheumatic Agents · Cytokines · Interleukin-17 · tocilizumab
참고문헌
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