Cargando…
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
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,...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893111/ https://www.ncbi.nlm.nih.gov/pubmed/27002108 http://dx.doi.org/10.1136/annrheumdis-2015-208267 |
_version_ | 1782435496485453824 |
---|---|
author | Conaghan, Philip G Østergaard, Mikkel Bowes, Michael A Wu, Chunying Fuerst, Thomas van der Heijde, Désirée Irazoque-Palazuelos, Fedra Soto-Raices, Oscar Hrycaj, Pawel Xie, Zhiyong Zhang, Richard Wyman, Bradley T Bradley, John D Soma, Koshika Wilkinson, Bethanie |
author_facet | Conaghan, Philip G Østergaard, Mikkel Bowes, Michael A Wu, Chunying Fuerst, Thomas van der Heijde, Désirée Irazoque-Palazuelos, Fedra Soto-Raices, Oscar Hrycaj, Pawel Xie, Zhiyong Zhang, Richard Wyman, Bradley T Bradley, John D Soma, Koshika Wilkinson, Bethanie |
author_sort | Conaghan, Philip G |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4893111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48931112016-06-09 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 Wu, Chunying Fuerst, Thomas van der Heijde, Désirée Irazoque-Palazuelos, Fedra Soto-Raices, Oscar Hrycaj, Pawel Xie, Zhiyong Zhang, Richard Wyman, Bradley T Bradley, John D Soma, Koshika Wilkinson, Bethanie Ann Rheum Dis Clinical and Epidemiological Research 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. BMJ Publishing Group 2016-06 2016-01-25 /pmc/articles/PMC4893111/ /pubmed/27002108 http://dx.doi.org/10.1136/annrheumdis-2015-208267 Text en 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/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Clinical and Epidemiological Research Conaghan, Philip G Østergaard, Mikkel Bowes, Michael A Wu, Chunying Fuerst, Thomas van der Heijde, Désirée Irazoque-Palazuelos, Fedra Soto-Raices, Oscar Hrycaj, Pawel Xie, Zhiyong Zhang, Richard Wyman, Bradley T Bradley, John D Soma, Koshika Wilkinson, Bethanie 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 |
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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Clinical and Epidemiological Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893111/ https://www.ncbi.nlm.nih.gov/pubmed/27002108 http://dx.doi.org/10.1136/annrheumdis-2015-208267 |
work_keys_str_mv | AT conaghanphilipg comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT østergaardmikkel comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT bowesmichaela comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT wuchunying comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT fuerstthomas comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT vanderheijdedesiree comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT irazoquepalazuelosfedra comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT sotoraicesoscar comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT hrycajpawel comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT xiezhiyong comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT zhangrichard comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT wymanbradleyt comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT bradleyjohnd comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT somakoshika comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques AT wilkinsonbethanie comparingtheeffectsoftofacitinibmethotrexateandthecombinationonbonemarrowoedemasynovitisandboneerosioninmethotrexatenaiveearlyactiverheumatoidarthritisresultsofanexploratoryrandomisedmristudyincorporatingsemiquantitativeandquantitativetechniques |