Does Periodontitis Affect the Treatment Response of Biologics in the Treatment of Rheumatoid Arthritis?

Masahiro Tachibana; Yukio Yonemoto; Koichi Okamura; Takahito Suto; Hideo Sakane; Tetsuya Kaneko; Trang Thuy Dam; Chisa Okura; Tsuyoshi Tajika; Yoshito Tsushima; Hirotaka Chikuda

Disclosures

Arthritis Res Ther. 2020;22(178)

Conclusion

There was a negative correlation between the extent of PD at baseline and the treatment response of RA in patients who received biological therapy. Therefore, the condition of periodontitis might affect ACPA levels and the treatment response of RA. The evaluation of periodontal condition is considered an essential part for the management of RA.

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Abbreviations
Δ: Differences in the values before and after treatment; ACPA: Anti-cyclic citrullinated peptide antibody; ACR: American College of Rheumatology; ADA: Adalimumab; CRP: C-reactive protein; csDMARDs: Conventional synthetic disease-modifying antirheumatic drugs; DAS: Disease activity score; ESR: Erythrocyte sedimentation rate; ETN: Etanercept; FDG-PET/CT: Fluorodeoxyglucose-positron emission tomography/computed tomography; IFX: Infliximab; MMP-3: Matrix metalloproteinase 3; MTX: Methotrexate; PD: Periodontitis; P. gingivalis: Porthyomonas gingivalis; PSL: Prednisolone; RA: Rheumatoid arthritis; RF: Rheumatoid factor; ROI: Region of interest; SUV: Standardized uptake value; SUVmax: Maximum standardized uptake value; TCZ: Tocilizumab; TNF: Tumor necrosis factor

Acknowledgements
The authors thank Nobuhiro Tahara in Kurume University School of Medicine for his contributions to the evaluation of the FDG uptake in this study.

Funding
There has been no significant financial support for this work that could have influenced its outcome. The authors acknowledge the financial support provided by a UCB Japan Grant (UCBJ Grant) for the English proofreading and article processing charge of the journal.

Availability of data and materials
All data generated or analyzed during this study are included in this published article and its supplementary information file.

Ethics approval and consent to participate
Ethical approval was obtained from the institutional review board of the Gunma University Hospital. Patients provided written informed consent before taking part in this study.

Arthritis Res Ther. 2020;22(178) © 2020 BioMed Central, Ltd.
Copyright to this article is held by the author(s), licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original citation.

Table 1. The characteristics and the parameters of all patients at baseline and after treatment
n = 60	Baseline	After treatment	p*
Age (year)	58.3 ± 14.1	–	–
Sex (male/female)	14/46	–	–
Disease duration (year)	13.3 ± 12.4	–	–
Steinbrocker stage (I/II/III/IV)	7/14/21/18	–	–
Steinbrocker class (1/2/3/4)	14/27/13/6	–	–
Concomitant MTX (%)	55	–	–
MTX dosage (mg/week)	8.91 ± 2.65	–	–
Concomitant PSL (%)	45	–	–
PSL dosage (mg/day)	3.70 ± 1.86	–	–
Smoking history (%)	10	–	–
ACPA positive (%)	80	–	–
CRP (mg/dl)	2.07 ± 2.21	0.50 ± 1.05	< 0.01
ESR (mm/h)	62.6 ± 31.4	35.3 ± 27.0	< 0.01
WBC (/μl)	6610 ± 2140	5582 ± 2067	< 0.01
RF (mg/dl)	256.0 ± 876.9	162.7 ± 551.9	0.43
ACPA (U/ml)	91.5 ± 117.1	75.2 ± 96.1	0.36
MMP-3 (ng/ml)	261.30 ± 243.82	118.65 ± 129.42	< 0.01
DAS28-CRP	4.07 ± 1.23	2.35 ± 1.01	< 0.01
Joints SUV	2.13 ± 0.65	1.67 ± 0.50	< 0.01
Periodontal SUV	1.83 ± 0.46	1.88 ± 0.45	0.39

*Wilcoxon's signed-rank test
Abbreviations: MTX methotrexate, PSL prednisolone, ACPA anti-cyclic citrullinated peptide antibody, CRP C-reactive protein, ESR erythrocyte sedimentation rate, WBC white blood cell, RF rheumatoid factor, MMP-3 matrix metalloproteinase 3, DAS Disease Activity Score

Table 2. Relationship between the periodontal SUV and the clinical parameters at baseline
	r	p*
ACPA (U/ml)	0.354	0.01
Age (year)	0.206	0.11
RF (mg/dl)	0.073	0.59
DAS28-CRP	−0.228	0.08
Disease duration (year)	0.049	0.72
WBC (/μl)	−0.029	0.83
MMP-3 (ng/ml)	−0.107	0.43

*Spearman's rank correlation test
Abbreviations: ACPA anti-cyclic citrullinated peptide antibody, RF rheumatoid factor, DAS Disease Activity Score, WBC white blood cell, MMP-3 matrix metalloproteinase 3

Table 3. Relationship between the periodontal SUV at baseline and the difference in the values before and after treatment
	r	p*
ΔACPA (U/ml)	0.179	0.132
ΔWBC (/μl)	−0.063	0.634
ΔRF (mg/dl)	0.059	0.659
ΔMMP-3 (ng/ml)	−0.211	0.108
ΔDAS28-CRP	−0.369	0.004

*Spearman's rank correlation test
Abbreviations: ESR erythrocyte sedimentation rate, WBC white blood cell, RF rheumatoid factor, ACPA anti-cyclic citrullinated peptide antibody, MMP-3 matrix metalloproteinase 3, DAS Disease Activity Score, Δ the difference in the values between before and after treatment

Table 4. Partial correlations between the periodontal SUVmax at baseline and ΔDAS28-CRP
Control variables		ΔDAS28-CRP
Age (year)	r	−0.288
Age (year)	p	0.027
Disease duration (year)	r	−2.777
Disease duration (year)	p	0.005
RF (mg/dl)	r	−0.27
RF (mg/dl)	p	0.043
Smoking history	r	−0.246
Smoking history	p	0.19
ACPA (U/ml)	r	−0.213
ACPA (U/ml)	p	0.118