Skip to main content
Erschienen in: Clinical Rheumatology 12/2021

16.07.2021 | Original Article

Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients

Erschienen in: Clinical Rheumatology | Ausgabe 12/2021

Einloggen, um Zugang zu erhalten

Abstract

Objective

Within rheumatoid arthritis (RA) patients treated with intravenous tocilizumab (IV-TCZ), it is unclear if power Doppler ultrasonography (PDUS) can predict future clinical response. This study sought to determine if baseline PDUS or its early changes can predict 12-week and 24-week disease activity outcomes, and quantify the need for dose escalation (4 to 8 mg/kg).

Methods

Fifty-four RA patients starting IV-TCZ were evaluated at baseline, 4, 6, 12, 16, and 24 weeks using 34-joint PDUS (US34-PDUS), clinical disease activity index (CDAI), 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR), ACR 20/50/70, health assessment questionnaire-disability index (HAQ-DI), and PDUS 20/50/70, a novel measure. Logistic regression models evaluated the predictive utility of US34-PDUS of DAS28-ESR response after adjusting for covariates.

Results

Ninety-four percent of patients required dose escalation to 8 mg/kg. US34-PDUS, CDAI, and DAS28-ESR improved significantly over 24 weeks (p < 0.001). Baseline PDUS and 12-week PDUS change correlated with CDAI at 24 weeks (p < 0.05). Logistic regression demonstrated baseline US34-PDUS was independently associated with DAS28-ESR ≥ 1.2 response, even after adjusting for baseline DAS28-ESR (p = 0.03). CDAI, DAS28-ESR, and their components increased across PDUS 20/50/70 categories; however, HAQ-DI did not.

Conclusion

RA patients treated with IV-TCZ for 24 weeks demonstrated significant improvement, and baseline/early changes in PDUS were predictive of later clinical response. The PDUS 20/50/70 measure is a novel metric of response. This study suggests that IV-TCZ 4 mg/kg may not be sufficient to attain low RA disease activity at 12 weeks, in RA patients with moderate to severe disease (DAS28 ≥ 4.4 and US34-PDUS ≥ 10).

Trial registration

ClinicalTrials.gov NCT01717859
Key Points
Over 90% of RA patients with baseline DAS28-ESR ≥ 4.4 and PDUS34 ≥ 10 required intravenous tocilizumab dose escalation from 4 to 8 mg/kg at 12 weeks.
Reduction in power Doppler ultrasonography (US34-PDUS) scores correlate with DAS28-ESR and CDAI over 24 weeks in rheumatoid arthritis patients with moderate to severe disease activity.
Baseline US34-PDUS predicts future improvements in clinical disease activity outcomes, independent of baseline DAS28-ESR.
Clinical response measures, DAS28-ESR and CDAI, improved across US34-PDUS 20/50/70 categories, while patient-reported outcomes did not.
Literatur
1.
Zurück zum Zitat Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67(11):1516–1523. https://doi.org/10.1136/ard.2008.092932CrossRefPubMed Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67(11):1516–1523. https://​doi.​org/​10.​1136/​ard.​2008.​092932CrossRefPubMed
2.
Zurück zum Zitat Strand V, Burmester GR, Ogale S, Devenport J, John A, Emery P (2012) Improvements in health-related quality of life after treatment with tocilizumab in patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study. Rheumatology (Oxford) 51(10):1860–1869. https://doi.org/10.1093/rheumatology/kes131CrossRef Strand V, Burmester GR, Ogale S, Devenport J, John A, Emery P (2012) Improvements in health-related quality of life after treatment with tocilizumab in patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study. Rheumatology (Oxford) 51(10):1860–1869. https://​doi.​org/​10.​1093/​rheumatology/​kes131CrossRef
7.
Zurück zum Zitat Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JMW, Hobbs K, Huizinga TWJ, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovský J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581. https://doi.org/10.1002/art.27584CrossRefPubMed Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JMW, Hobbs K, Huizinga TWJ, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovský J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581. https://​doi.​org/​10.​1002/​art.​27584CrossRefPubMed
8.
Zurück zum Zitat Ben-Artzi A, Kaeley G, Ranganath VK (2021) Ultrasound scoring of joint synovitis: objective quantification of articular inflammation. Springer International Publishing Ben-Artzi A, Kaeley G, Ranganath VK (2021) Ultrasound scoring of joint synovitis: objective quantification of articular inflammation. Springer International Publishing
11.
Zurück zum Zitat Backhaus M, Ohrndorf S, Kellner H, Strunk J, Backhaus TM, Hartung W, Sattler H, Albrecht K, Kaufmann J, Becker K, Sorensen H, Meier L, Burmester GR, Schmidt WA (2009) Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum 61(9):1194–1201. https://doi.org/10.1002/art.24646CrossRefPubMed Backhaus M, Ohrndorf S, Kellner H, Strunk J, Backhaus TM, Hartung W, Sattler H, Albrecht K, Kaufmann J, Becker K, Sorensen H, Meier L, Burmester GR, Schmidt WA (2009) Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum 61(9):1194–1201. https://​doi.​org/​10.​1002/​art.​24646CrossRefPubMed
14.
Zurück zum Zitat Curtis JR, Yang S, Chen L, Pope JE, Keystone EC, Haraoui B, Boire G, Thorne JC, Tin D, Hitchon CA, Bingham CO 3rd, Bykerk VP (2015) Determining the minimally important difference in the clinical disease activity index for improvement and worsening in early rheumatoid arthritis patients. Arthritis Care Res (Hoboken) 67(10):1345–1353. https://doi.org/10.1002/acr.22606CrossRef Curtis JR, Yang S, Chen L, Pope JE, Keystone EC, Haraoui B, Boire G, Thorne JC, Tin D, Hitchon CA, Bingham CO 3rd, Bykerk VP (2015) Determining the minimally important difference in the clinical disease activity index for improvement and worsening in early rheumatoid arthritis patients. Arthritis Care Res (Hoboken) 67(10):1345–1353. https://​doi.​org/​10.​1002/​acr.​22606CrossRef
15.
16.
Zurück zum Zitat Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri DA, Tomsic M, Alecock E, Woodworth T, Genovese MC (2010) Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 69(1):88–96. https://doi.org/10.1136/ard.2008.105197CrossRefPubMed Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri DA, Tomsic M, Alecock E, Woodworth T, Genovese MC (2010) Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 69(1):88–96. https://​doi.​org/​10.​1136/​ard.​2008.​105197CrossRefPubMed
17.
Zurück zum Zitat Hama M, Uehara T, Takase K, Ihata A, Ueda A, Takeno M, Shizukuishi K, Tateishi U, Ishigatsubo Y (2012) Power Doppler ultrasonography is useful for assessing disease activity and predicting joint destruction in rheumatoid arthritis patients receiving tocilizumab–preliminary data. Rheumatol Int 32(5):1327–1333. https://doi.org/10.1007/s00296-011-1802-5CrossRefPubMed Hama M, Uehara T, Takase K, Ihata A, Ueda A, Takeno M, Shizukuishi K, Tateishi U, Ishigatsubo Y (2012) Power Doppler ultrasonography is useful for assessing disease activity and predicting joint destruction in rheumatoid arthritis patients receiving tocilizumab–preliminary data. Rheumatol Int 32(5):1327–1333. https://​doi.​org/​10.​1007/​s00296-011-1802-5CrossRefPubMed
18.
Zurück zum Zitat Kume K, Amano K, Yamada S, Hatta K, Kuwaba N, Ohta H (2011) Very early improvements in the wrist and hand assessed by power Doppler sonography predicting later favorable responses in tocilizumab-treated patients with rheumatoid arthritis. Arthritis Care Res (Hoboken) 63(10):1477–1481. https://doi.org/10.1002/acr.20537CrossRef Kume K, Amano K, Yamada S, Hatta K, Kuwaba N, Ohta H (2011) Very early improvements in the wrist and hand assessed by power Doppler sonography predicting later favorable responses in tocilizumab-treated patients with rheumatoid arthritis. Arthritis Care Res (Hoboken) 63(10):1477–1481. https://​doi.​org/​10.​1002/​acr.​20537CrossRef
19.
Zurück zum Zitat Kawashiri SY, Suzuki T, Nakashima Y, Horai Y, Okada A, Iwamoto N, Ichinose K, Tamai M, Arima K, Nakamura H, Origuchi T, Uetani M, Aoyagi K, Kawakami A (2015) Confirmation of effectiveness of tocilizumab by ultrasonography and magnetic resonance imaging in biologic agent-naïve early-stage rheumatoid arthritis patients. Mod Rheumatol 25(6):948–953. https://doi.org/10.3109/14397595.2013.844394CrossRefPubMed Kawashiri SY, Suzuki T, Nakashima Y, Horai Y, Okada A, Iwamoto N, Ichinose K, Tamai M, Arima K, Nakamura H, Origuchi T, Uetani M, Aoyagi K, Kawakami A (2015) Confirmation of effectiveness of tocilizumab by ultrasonography and magnetic resonance imaging in biologic agent-naïve early-stage rheumatoid arthritis patients. Mod Rheumatol 25(6):948–953. https://​doi.​org/​10.​3109/​14397595.​2013.​844394CrossRefPubMed
20.
Zurück zum Zitat Hammer HB, Hansen I, Järvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L (2021) Major reduction of ultrasound-detected synovitis during subcutaneous tocilizumab treatment: results from a multicentre 24 week study of patients with rheumatoid arthritis. Scand J Rheumatol:1–9. https://doi.org/10.1080/03009742.2020.1845394 Hammer HB, Hansen I, Järvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L (2021) Major reduction of ultrasound-detected synovitis during subcutaneous tocilizumab treatment: results from a multicentre 24 week study of patients with rheumatoid arthritis. Scand J Rheumatol:1–9. https://​doi.​org/​10.​1080/​03009742.​2020.​1845394
21.
Zurück zum Zitat Nguyen H, Ruyssen-Witrand A, Gandjbakhch F, Constantin A, Foltz V, Cantagrel A (2014) Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural progression in rheumatoid arthritis patients in clinical remission: a systematic review and meta-analysis. Rheumatology (Oxford) 53(11):2110–2118. https://doi.org/10.1093/rheumatology/keu217CrossRef Nguyen H, Ruyssen-Witrand A, Gandjbakhch F, Constantin A, Foltz V, Cantagrel A (2014) Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural progression in rheumatoid arthritis patients in clinical remission: a systematic review and meta-analysis. Rheumatology (Oxford) 53(11):2110–2118. https://​doi.​org/​10.​1093/​rheumatology/​keu217CrossRef
23.
Zurück zum Zitat 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 (2011) 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. Skelet Radiol 40(6):745–755. https://doi.org/10.1007/s00256-010-1064-4CrossRef 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 (2011) 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. Skelet Radiol 40(6):745–755. https://​doi.​org/​10.​1007/​s00256-010-1064-4CrossRef
Metadaten
Titel
Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients
Publikationsdatum
16.07.2021
Erschienen in
Clinical Rheumatology / Ausgabe 12/2021
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-021-05857-7

Weitere Artikel der Ausgabe 12/2021

Clinical Rheumatology 12/2021 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Strenge Blutdruckeinstellung lohnt auch im Alter noch

30.04.2024 Arterielle Hypertonie Nachrichten

Ältere Frauen, die von chronischen Erkrankungen weitgehend verschont sind, haben offenbar die besten Chancen, ihren 90. Geburtstag zu erleben, wenn ihr systolischer Blutdruck < 130 mmHg liegt. Das scheint selbst für 80-Jährige noch zu gelten.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.