Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques

Philip G Conaghan; Mikkel Østergaard; Michael A Bowes; Chunying Wu; Thomas Fuerst; Désirée van der Heijde; Fedra Irazoque-Palazuelos; Oscar Soto-Raices; Pawel Hrycaj; Zhiyong Xie; Richard Zhang; Bradley T Wyman; John D Bradley; Koshika Soma; Bethanie Wilkinson

doi:10.1136/annrheumdis-2015-208267

Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques

Philip G Conaghan, Mikkel Østergaard, Michael A Bowes, Chunying Wu, Thomas Fuerst, Désirée van der Heijde, Fedra Irazoque-Palazuelos, Oscar Soto-Raices, Pawel Hrycaj, Zhiyong Xie, Richard Zhang, Bradley T Wyman, John D Bradley, Koshika Soma, Bethanie Wilkinson

Afdeling for Rygkirurgi, Led- og Bindevævssygdomme HOC

94 Citationer (Scopus)

Abstract

OBJECTIVES: To explore the effects of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)-with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand.

METHODS: In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant.

RESULTS: In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were -1.55 (90% CI -2.52 to -0.58) for tofacitinib + MTX and -1.74 (-2.72 to -0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were -0.63 (-1.58 to 0.31) for tofacitinib + MTX and -0.52 (-1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy.

CONCLUSIONS: These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage.

TRIAL REGISTRATION NUMBER: NCT01164579.

Originalsprog	Engelsk
Tidsskrift	Annals of the Rheumatic Diseases
Vol/bind	75
Udgave nummer	6
Sider (fra-til)	1024-33
Antal sider	10
ISSN	0003-4967
DOI	https://doi.org/10.1136/annrheumdis-2015-208267
Status	Udgivet - jun. 2016

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Citationsformater

Conaghan, P. G., Østergaard, M., Bowes, M. A., Wu, C., Fuerst, T., van der Heijde, D., Irazoque-Palazuelos, F., Soto-Raices, O., Hrycaj, P., Xie, Z., Zhang, R., Wyman, B. T., Bradley, J. D., Soma, K., & Wilkinson, B. (2016). Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. Annals of the Rheumatic Diseases, 75(6), 1024-33. https://doi.org/10.1136/annrheumdis-2015-208267

Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. / Conaghan, Philip G; Østergaard, Mikkel; Bowes, Michael A et al.
I: Annals of the Rheumatic Diseases, Bind 75, Nr. 6, 06.2016, s. 1024-33.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Conaghan, PG, Østergaard, M, Bowes, MA, Wu, C, Fuerst, T, van der Heijde, D, Irazoque-Palazuelos, F, Soto-Raices, O, Hrycaj, P, Xie, Z, Zhang, R, Wyman, BT, Bradley, JD, Soma, K & Wilkinson, B 2016, 'Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques', Annals of the Rheumatic Diseases, bind 75, nr. 6, s. 1024-33. https://doi.org/10.1136/annrheumdis-2015-208267

Conaghan PG, Østergaard M, Bowes MA, Wu C, Fuerst T, van der Heijde D et al. Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. Annals of the Rheumatic Diseases. 2016 jun.;75(6):1024-33. doi: 10.1136/annrheumdis-2015-208267

Conaghan, Philip G ; Østergaard, Mikkel ; Bowes, Michael A et al. / Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis : results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. I: Annals of the Rheumatic Diseases. 2016 ; Bind 75, Nr. 6. s. 1024-33.

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title = "Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques",

abstract = "OBJECTIVES: To explore the effects of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)-with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand.METHODS: In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant.RESULTS: In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were -1.55 (90\% CI -2.52 to -0.58) for tofacitinib + MTX and -1.74 (-2.72 to -0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were -0.63 (-1.58 to 0.31) for tofacitinib + MTX and -0.52 (-1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy.CONCLUSIONS: These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage.TRIAL REGISTRATION NUMBER: NCT01164579.",

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author = "Conaghan, \{Philip G\} and Mikkel {\O}stergaard and Bowes, \{Michael A\} and Chunying Wu and Thomas Fuerst and \{van der Heijde\}, D{\'e}sir{\'e}e and Fedra Irazoque-Palazuelos and Oscar Soto-Raices and Pawel Hrycaj and Zhiyong Xie and Richard Zhang and Wyman, \{Bradley T\} and Bradley, \{John D\} and Koshika Soma and Bethanie Wilkinson",

note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/",

year = "2016",

month = jun,

doi = "10.1136/annrheumdis-2015-208267",

language = "English",

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TY - JOUR

T1 - Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis

T2 - results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques

AU - Conaghan, Philip G

AU - Østergaard, Mikkel

AU - Bowes, Michael A

AU - Wu, Chunying

AU - Fuerst, Thomas

AU - van der Heijde, Désirée

AU - Irazoque-Palazuelos, Fedra

AU - Soto-Raices, Oscar

AU - Hrycaj, Pawel

AU - Xie, Zhiyong

AU - Zhang, Richard

AU - Wyman, Bradley T

AU - Bradley, John D

AU - Soma, Koshika

AU - Wilkinson, Bethanie

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PY - 2016/6

Y1 - 2016/6

N2 - OBJECTIVES: To explore the effects of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)-with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand.METHODS: In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant.RESULTS: In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were -1.55 (90% CI -2.52 to -0.58) for tofacitinib + MTX and -1.74 (-2.72 to -0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were -0.63 (-1.58 to 0.31) for tofacitinib + MTX and -0.52 (-1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy.CONCLUSIONS: These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage.TRIAL REGISTRATION NUMBER: NCT01164579.

AB - OBJECTIVES: To explore the effects of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)-with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand.METHODS: In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant.RESULTS: In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were -1.55 (90% CI -2.52 to -0.58) for tofacitinib + MTX and -1.74 (-2.72 to -0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were -0.63 (-1.58 to 0.31) for tofacitinib + MTX and -0.52 (-1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy.CONCLUSIONS: These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage.TRIAL REGISTRATION NUMBER: NCT01164579.

KW - Journal Article

UR - https://www.scopus.com/pages/publications/84962179941

U2 - 10.1136/annrheumdis-2015-208267

DO - 10.1136/annrheumdis-2015-208267

M3 - Journal article

C2 - 27002108

SN - 0003-4967

VL - 75

SP - 1024

EP - 1033

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 6

ER -