Skip to main content
Top
Published in: BMC Musculoskeletal Disorders 1/2014

Open Access 01-12-2014 | Research article

Evaluation of tocilizumab therapy in patients with rheumatoid arthritis based on FDG-PET/CT

Authors: Koichi Okamura, Yukio Yonemoto, Chisa Okura, Tetsuya Higuchi, Yoshito Tsushima, Kenji Takagishi

Published in: BMC Musculoskeletal Disorders | Issue 1/2014

Login to get access

Abstract

Background

Positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) can detect the presence of synovitis in rheumatoid arthritis (RA) patients. The aim of this study was to investigate whether the findings of FDG-PET matched the conventional assessments of the disease activity score (DAS) 28, DAS28-CRP, simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in RA patients receiving tocilizumab (TCZ) therapy.

Methods

Seventeen RA patients treated with TCZ were assessed. FDG-PET was performed at baseline and three and six months after the initiation of TCZ therapy. The maximum SUV (SUVmax) of the bilateral shoulder, elbow, wrist, hip, knee and ankle joints were added together (total SUV) and were used to assess the degree of FDG uptake as a representative parameter. The correlations between the ΔSUV and the difference in the clinical parameters at baseline and at each observation period, and the differences in each clinical parameters, were assessed.

Results

The ΔSUV, the differences in the total SUV at baseline and at three/six months after starting treatment positively correlated with the ΔDAS28 (r = 0.615 p = 0.009/ r = 0.775 p < 0.001), ΔDAS28-CRP (r = 0.696, p = 0.002/ r = 0.828, p < 0.001), ΔSDAI (r = 0.652, p = 0.005/ r = 0.686, p = 0.002) and ΔCDAI (r = 0.662, p = 0.004/ r = 0.711, p = 0.001) for each period. The total SUV was significantly decreased at three and six months after the initiation of TCZ (p < 0.05).

Conclusions

A reduction in the FDG uptake was observed at three and six months after the initiation of TCZ therapy. The disease activity estimated on FDG-PET/CT matched the conventional parameters following the TCZ therapy in RA patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Kiely PD, Deighton C, Dixey J, Ostör AJ: Biologic agents for rheumatoid arthritis–negotiating the NICE technology appraisals. Rheumatology (Oxford). 2012, 51: 24-31. 10.1093/rheumatology/ker321.CrossRef Kiely PD, Deighton C, Dixey J, Ostör AJ: Biologic agents for rheumatoid arthritis–negotiating the NICE technology appraisals. Rheumatology (Oxford). 2012, 51: 24-31. 10.1093/rheumatology/ker321.CrossRef
2.
go back to reference Ogata A, Hirano T, Hishitani Y, Tanaka T: Safety and efficacy of tocilizumab for the treatment of rheumatoid arthritis. Clin Med Insights Arthritis Musculoskelet Disord. 2012, 5: 27-42.PubMedPubMedCentral Ogata A, Hirano T, Hishitani Y, Tanaka T: Safety and efficacy of tocilizumab for the treatment of rheumatoid arthritis. Clin Med Insights Arthritis Musculoskelet Disord. 2012, 5: 27-42.PubMedPubMedCentral
3.
go back to reference Nishimoto N, Kishimoto T: Humanized antihuman IL-6 receptor antibody, tocilizumab. Handb Exp Pharmacol. 2008, 181: 151-160. 10.1007/978-3-540-73259-4_7.CrossRefPubMed Nishimoto N, Kishimoto T: Humanized antihuman IL-6 receptor antibody, tocilizumab. Handb Exp Pharmacol. 2008, 181: 151-160. 10.1007/978-3-540-73259-4_7.CrossRefPubMed
4.
go back to reference Nishimoto N, Yoshizaki K, Maeda K, Kuritani T, Deguchi H, Sato B, Imai N, Suemura M, Kakehi T, Takagi N, Kishimoto T: Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol. 2003, 30: 1426-1435.PubMed Nishimoto N, Yoshizaki K, Maeda K, Kuritani T, Deguchi H, Sato B, Imai N, Suemura M, Kakehi T, Takagi N, Kishimoto T: Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol. 2003, 30: 1426-1435.PubMed
5.
go back to reference Funahashi K, Koyano S, Miura T, Hagiwara T, Okuda K, Matsubara T: Efficacy of tocilizumab and evaluation of clinical remission as determined by CDAI and MMP-3 level. Mod Rheumatol. 2009, 19: 507-512. 10.3109/s10165-009-0203-z.CrossRefPubMed Funahashi K, Koyano S, Miura T, Hagiwara T, Okuda K, Matsubara T: Efficacy of tocilizumab and evaluation of clinical remission as determined by CDAI and MMP-3 level. Mod Rheumatol. 2009, 19: 507-512. 10.3109/s10165-009-0203-z.CrossRefPubMed
6.
go back to reference Kaneko A, Kida D, Saito K, Tsukamoto M, Sato T: Clinical results for tocilizumab over one year in the clinical setting as assessed by CDAI (clinical disease activity index): CRP at week 12 and MMP-3 at week 24 are predictive factors for CDAI. Rheumatol Int. 2012, 32: 3631-3637. 10.1007/s00296-011-2256-5.CrossRefPubMed Kaneko A, Kida D, Saito K, Tsukamoto M, Sato T: Clinical results for tocilizumab over one year in the clinical setting as assessed by CDAI (clinical disease activity index): CRP at week 12 and MMP-3 at week 24 are predictive factors for CDAI. Rheumatol Int. 2012, 32: 3631-3637. 10.1007/s00296-011-2256-5.CrossRefPubMed
7.
go back to reference Mierau M, Schoels M, Gonda G, Fuchs J, Aletaha D, Smolen JS: Assessing remission in clinical practice. Rheumatology (Oxford). 2007, 46: 975-979. 10.1093/rheumatology/kem007.CrossRef Mierau M, Schoels M, Gonda G, Fuchs J, Aletaha D, Smolen JS: Assessing remission in clinical practice. Rheumatology (Oxford). 2007, 46: 975-979. 10.1093/rheumatology/kem007.CrossRef
8.
go back to reference Smolen JS, Landewé R, Breedveld FC, Buch M, Burmester G, Dougados M, Emery P, Gaujoux-Viala C, Gossec L, Nam J, Ramiro S, Winthrop K, de Wit M, Aletaha D, Betteridge N, Bijlsma JW, Boers M, Buttgereit F, Combe B, Cutolo M, Damjanov N, Hazes JM, Kouloumas M, Kvien TK, Mariette X, Pavelka K, van Riel PL, Rubbert-Roth A, Scholte-Voshaar M, Scott DL, et al: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014, 73: 492-509.CrossRefPubMed Smolen JS, Landewé R, Breedveld FC, Buch M, Burmester G, Dougados M, Emery P, Gaujoux-Viala C, Gossec L, Nam J, Ramiro S, Winthrop K, de Wit M, Aletaha D, Betteridge N, Bijlsma JW, Boers M, Buttgereit F, Combe B, Cutolo M, Damjanov N, Hazes JM, Kouloumas M, Kvien TK, Mariette X, Pavelka K, van Riel PL, Rubbert-Roth A, Scholte-Voshaar M, Scott DL, et al: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014, 73: 492-509.CrossRefPubMed
9.
go back to reference Wang SC, Xie Q, Lv WF: Positron emission tomography/computed tomography imaging and rheumatoid arthritis. Int J Rheum Dis. 2014, 17: 248-255. 10.1111/1756-185X.12316.CrossRefPubMed Wang SC, Xie Q, Lv WF: Positron emission tomography/computed tomography imaging and rheumatoid arthritis. Int J Rheum Dis. 2014, 17: 248-255. 10.1111/1756-185X.12316.CrossRefPubMed
10.
go back to reference McQueen FM, Ostergaard M: Established rheumatoid arthritis - new imaging modalities. Best Pract Res Clin Rheumatol. 2007, 21: 841-856. 10.1016/j.berh.2007.05.001.CrossRefPubMed McQueen FM, Ostergaard M: Established rheumatoid arthritis - new imaging modalities. Best Pract Res Clin Rheumatol. 2007, 21: 841-856. 10.1016/j.berh.2007.05.001.CrossRefPubMed
11.
go back to reference Beckers C, Jeukens X, Ribbens C, André B, Marcelis S, Leclercq P, Kaiser MJ, Foidart J, Hustinx R, Malaise MG: (18)F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resonance and sonographic assessments as well as with the serum level of metalloproteinase-3. Eur J Nucl Med Mol Imaging. 2006, 33: 275-280. 10.1007/s00259-005-1952-3.CrossRefPubMed Beckers C, Jeukens X, Ribbens C, André B, Marcelis S, Leclercq P, Kaiser MJ, Foidart J, Hustinx R, Malaise MG: (18)F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resonance and sonographic assessments as well as with the serum level of metalloproteinase-3. Eur J Nucl Med Mol Imaging. 2006, 33: 275-280. 10.1007/s00259-005-1952-3.CrossRefPubMed
12.
go back to reference Palmer WE, Rosenthal DI, Schoenberg OI, Fischman AJ, Simon LS, Rubin RH, Polisson RP: Quantification of inflammation in the wrist with gadolinium-enhanced MR imaging and PET with 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology. 1995, 196: 647-655. 10.1148/radiology.196.3.7644624.CrossRefPubMed Palmer WE, Rosenthal DI, Schoenberg OI, Fischman AJ, Simon LS, Rubin RH, Polisson RP: Quantification of inflammation in the wrist with gadolinium-enhanced MR imaging and PET with 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology. 1995, 196: 647-655. 10.1148/radiology.196.3.7644624.CrossRefPubMed
13.
go back to reference Polisson RP, Schoenberg OI, Fischman A, Rubin R, Simon LS, Rosenthal D, Palmer WE: Use of magnetic resonance imaging and positron emission tomography in the assessment of synovial volume and glucose metabolism in patients with rheumatoid arthritis. Arthritis Rheum. 1995, 38: 819-825. 10.1002/art.1780380616.CrossRefPubMed Polisson RP, Schoenberg OI, Fischman A, Rubin R, Simon LS, Rosenthal D, Palmer WE: Use of magnetic resonance imaging and positron emission tomography in the assessment of synovial volume and glucose metabolism in patients with rheumatoid arthritis. Arthritis Rheum. 1995, 38: 819-825. 10.1002/art.1780380616.CrossRefPubMed
14.
go back to reference Goerres GW, Forster A, Uebelhart D, Seifert B, Treyer V, Michel B, von Schulthess GK, Kaim AH: F-18 FDG whole-body PET for the assessment of disease activity in patients with rheumatoid arthritis. Clin Nucl Med. 2006, 31: 386-390. 10.1097/01.rlu.0000222678.95218.42.CrossRefPubMed Goerres GW, Forster A, Uebelhart D, Seifert B, Treyer V, Michel B, von Schulthess GK, Kaim AH: F-18 FDG whole-body PET for the assessment of disease activity in patients with rheumatoid arthritis. Clin Nucl Med. 2006, 31: 386-390. 10.1097/01.rlu.0000222678.95218.42.CrossRefPubMed
15.
go back to reference Vijayant V, Sarma M, Aurangabadkar H, Bichile L, Basu S: Potential of (18)F-FDG-PET as a valuable adjunct to clinical and response assessment in rheumatoid arthritis and seronegative spondyloarthropathies. World J Radiol. 2012, 4: 462-468. 10.4329/wjr.v4.i12.462.CrossRefPubMedPubMedCentral Vijayant V, Sarma M, Aurangabadkar H, Bichile L, Basu S: Potential of (18)F-FDG-PET as a valuable adjunct to clinical and response assessment in rheumatoid arthritis and seronegative spondyloarthropathies. World J Radiol. 2012, 4: 462-468. 10.4329/wjr.v4.i12.462.CrossRefPubMedPubMedCentral
16.
go back to reference Roivainen A, Hautaniemi S, Möttönen T, Nuutila P, Oikonen V, Parkkola R, Pricop L, Ress R, Seneca N, Seppänen M, Yli-Kerttula T: Correlation of 18F-FDG PET/CT assessments with disease activity and markers of inflammation in patients with early rheumatoid arthritis following the initiation of combination therapy with triple oral antirheumatic drugs. Eur J Nucl Med Mol Imaging. 2013, 40: 403-410. 10.1007/s00259-012-2282-x.CrossRefPubMed Roivainen A, Hautaniemi S, Möttönen T, Nuutila P, Oikonen V, Parkkola R, Pricop L, Ress R, Seneca N, Seppänen M, Yli-Kerttula T: Correlation of 18F-FDG PET/CT assessments with disease activity and markers of inflammation in patients with early rheumatoid arthritis following the initiation of combination therapy with triple oral antirheumatic drugs. Eur J Nucl Med Mol Imaging. 2013, 40: 403-410. 10.1007/s00259-012-2282-x.CrossRefPubMed
17.
go back to reference Beckers C, Ribbens C, André B, Marcelis S, Kaye O, Mathy L, Kaiser MJ, Hustinx R, Foidart J, Malaise MG: Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET. J Null Med. 2004, 45: 956-964. Beckers C, Ribbens C, André B, Marcelis S, Kaye O, Mathy L, Kaiser MJ, Hustinx R, Foidart J, Malaise MG: Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET. J Null Med. 2004, 45: 956-964.
18.
go back to reference Okamura K, Yonemoto Y, Arisaka Y, Takeuchi K, Kobayashi T, Oriuchi N, Tsushima Y, Takagishi K: The assessment of biologic treatment in patients with rheumatoid arthritis using FDG-PET/CT. Rheumatology (Oxford). 2012, 51: 1484-1491. 10.1093/rheumatology/kes064.CrossRef Okamura K, Yonemoto Y, Arisaka Y, Takeuchi K, Kobayashi T, Oriuchi N, Tsushima Y, Takagishi K: The assessment of biologic treatment in patients with rheumatoid arthritis using FDG-PET/CT. Rheumatology (Oxford). 2012, 51: 1484-1491. 10.1093/rheumatology/kes064.CrossRef
19.
go back to reference Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller PJ, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.CrossRefPubMed Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller PJ, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.CrossRefPubMed
21.
go back to reference Smolen JS, Breedveld FC, Schiff MH, Kalden JR, Emery P, Eberl G, van Riel PL, Tugwell P: A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology (Oxford). 2003, 42: 244-257. 10.1093/rheumatology/keg072.CrossRef Smolen JS, Breedveld FC, Schiff MH, Kalden JR, Emery P, Eberl G, van Riel PL, Tugwell P: A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology (Oxford). 2003, 42: 244-257. 10.1093/rheumatology/keg072.CrossRef
22.
go back to reference Aletaha D, Smolen J: The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): A review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol. 2005, 23: S100-S108.PubMed Aletaha D, Smolen J: The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): A review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol. 2005, 23: S100-S108.PubMed
23.
go back to reference Curtin F, Schulz P: Multiple correlations and Bonferroni’s correction. Biol Psychiatry. 1998, 44: 775-777. 10.1016/S0006-3223(98)00043-2.CrossRefPubMed Curtin F, Schulz P: Multiple correlations and Bonferroni’s correction. Biol Psychiatry. 1998, 44: 775-777. 10.1016/S0006-3223(98)00043-2.CrossRefPubMed
24.
go back to reference Mihara M, Moriya Y, Kishimoto T, Ohsugi Y: Interleukin-6 (IL-6) induces the proliferation of synovial fibroblastic cells in the presence of soluble IL-6 receptor. Br J Rheumatol. 1995, 34: 321-325. 10.1093/rheumatology/34.4.321.CrossRefPubMed Mihara M, Moriya Y, Kishimoto T, Ohsugi Y: Interleukin-6 (IL-6) induces the proliferation of synovial fibroblastic cells in the presence of soluble IL-6 receptor. Br J Rheumatol. 1995, 34: 321-325. 10.1093/rheumatology/34.4.321.CrossRefPubMed
25.
go back to reference Mihara M, Moriya Y, Kishimoto T, Ohsugi Y: Treatment of rheumatoid synovitis with anti-reshaping human interleukin-6 receptor monoclonal antibody. Arthritis Rheum. 1998, 41: 2014-2021. 10.1002/1529-0131(199811)41:11<2014::AID-ART17>3.0.CO;2-T.CrossRef Mihara M, Moriya Y, Kishimoto T, Ohsugi Y: Treatment of rheumatoid synovitis with anti-reshaping human interleukin-6 receptor monoclonal antibody. Arthritis Rheum. 1998, 41: 2014-2021. 10.1002/1529-0131(199811)41:11<2014::AID-ART17>3.0.CO;2-T.CrossRef
26.
go back to reference Hashizume M, Hayakawa N, Suzuki M, Mihara M: IL-6/sIL-6R trans-signalling, but not TNF-alpha induced angiogenesis in a HUVEC and synovial cell co-culture system. Rheumatol Int. 2009, 29: 1449-1454. 10.1007/s00296-009-0885-8.CrossRefPubMed Hashizume M, Hayakawa N, Suzuki M, Mihara M: IL-6/sIL-6R trans-signalling, but not TNF-alpha induced angiogenesis in a HUVEC and synovial cell co-culture system. Rheumatol Int. 2009, 29: 1449-1454. 10.1007/s00296-009-0885-8.CrossRefPubMed
27.
go back to reference Suzuki M, Hashizume M, Yoshida H, Mihara M: Anti-inflammatory mechanism of tocilizumab, a humanized anti-IL-6R antibody: effect on the expression of chemokine and adhesion molecule. Rheumatol Int. 2010, 30: 309-315. 10.1007/s00296-009-0953-0.CrossRefPubMed Suzuki M, Hashizume M, Yoshida H, Mihara M: Anti-inflammatory mechanism of tocilizumab, a humanized anti-IL-6R antibody: effect on the expression of chemokine and adhesion molecule. Rheumatol Int. 2010, 30: 309-315. 10.1007/s00296-009-0953-0.CrossRefPubMed
28.
go back to reference Nakatani A, Takahashi M, Momose T, Ohtomo K, Koyasu S: Inflammatory cytokines and hypoxia contribute to 18F-FDG uptake by cells involved in pannus formation in rheumatoid arthritis. J Nucl Med. 2009, 50: 920-926. 10.2967/jnumed.108.060103.CrossRefPubMed Nakatani A, Takahashi M, Momose T, Ohtomo K, Koyasu S: Inflammatory cytokines and hypoxia contribute to 18F-FDG uptake by cells involved in pannus formation in rheumatoid arthritis. J Nucl Med. 2009, 50: 920-926. 10.2967/jnumed.108.060103.CrossRefPubMed
29.
go back to reference Kamishima T, Tanimura K, Shimizu M, Matsuhashi M, Fukae J, Kon Y, Hagiwara H, Narita A, Aoki Y, Kosaka N, Atsumi T, Shirato H, Terae S: Monitoring anti-interleukin 6 receptor antibody treatment for rheumatoid arthritis by quantitative magnetic resonance imaging of the hand and power Doppler ultrasonography of the finger. Skeletal Radiol. 2011, 40: 745-755. 10.1007/s00256-010-1064-4.CrossRefPubMed Kamishima T, Tanimura K, Shimizu M, Matsuhashi M, Fukae J, Kon Y, Hagiwara H, Narita A, Aoki Y, Kosaka N, Atsumi T, Shirato H, Terae S: Monitoring anti-interleukin 6 receptor antibody treatment for rheumatoid arthritis by quantitative magnetic resonance imaging of the hand and power Doppler ultrasonography of the finger. Skeletal Radiol. 2011, 40: 745-755. 10.1007/s00256-010-1064-4.CrossRefPubMed
30.
go back to reference Suzuki T, Horikoshi M, Sugihara M, Hirota T, Ogishima H, Umeda N, Kondo Y, Tsuboi H, Hayashi T, Chino Y, Matsumoto I, Sumida T: Therapeutic efficacy of tocilizumab in patients with rheumatoid arthritis refractory to anti-tumor-necrosis-factor inhibitors: 1 year follow-up with low-field extremity MRI. Mod Rheumatol. 2013, 23: 782-787. 10.3109/s10165-012-0746-2.CrossRefPubMed Suzuki T, Horikoshi M, Sugihara M, Hirota T, Ogishima H, Umeda N, Kondo Y, Tsuboi H, Hayashi T, Chino Y, Matsumoto I, Sumida T: Therapeutic efficacy of tocilizumab in patients with rheumatoid arthritis refractory to anti-tumor-necrosis-factor inhibitors: 1 year follow-up with low-field extremity MRI. Mod Rheumatol. 2013, 23: 782-787. 10.3109/s10165-012-0746-2.CrossRefPubMed
Metadata
Title
Evaluation of tocilizumab therapy in patients with rheumatoid arthritis based on FDG-PET/CT
Authors
Koichi Okamura
Yukio Yonemoto
Chisa Okura
Tetsuya Higuchi
Yoshito Tsushima
Kenji Takagishi
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2014
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-15-393

Other articles of this Issue 1/2014

BMC Musculoskeletal Disorders 1/2014 Go to the issue