Young Ho Lee1, Gwan Gyu Song2. 1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of). lyhcgh@korea.ac.kr. 2. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of).
Abstract
OBJECTIVES: The relative remission rates of tofacitinib, baricitinib, upadacitinib, and filgotinib compared with those of adalimumab were assessed in patients with rheumatoid arthritis (RA) who responded poorly to methotrexate (MTX). METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the Disease Activity Score in 28 joints with C‑reactive protein (DAS28-CRP), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and the Boolean remission of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients with inadequate responses to MTX. RESULTS: Four RCTs, comprising 3507 patients, met the inclusion criteria. The filgotinib 200 mg + MTX and upadacitinib 15 mg + MTX groups showed a significantly higher DAS28-CRP < 2.6 than adalimumab 40 mg + MTX. Upadacitinib 15 mg + MTX showed a significantly higher CDAI (≤ 2.8) than adalimumab 40 mg + MTX (odds ratio [OR]: 1.62; 95% credible interval [CrI]: 1.16-2.29). The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX had the highest probability of being the best treatment as it achieved a CDAI ≤ 2.8, followed by filgotinib 200 mg + MTX, baricitinib 4 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab 40 mg + MTX. The Boolean remission showed the same distribution pattern as that of the CDAI ≤ 2.8. Upadacitinib 15 mg + MTX showed a significantly higher SDAI ≤ 3.3 than adalimumab 40 mg + MTX (OR: 1.62; 95% CrI: 1.16-2.28). SUCRA ranking based on SDAI ≤ 3.3 indicated that upadacitinib 15 mg + MTX had the highest probability of being the best treatment for achieving an SDAI ≤ 3.3, followed by baricitinib 4 mg + MTX, filgotinib 200 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab 40 mg + MTX. CONCLUSIONS: In RA patients with an inadequate response to MTX, remission rates with JAK inhibitors were significantly higher; there is evidence for differences in efficacy regarding remission among the different JAK inhibitors.
OBJECTIVES: The relative remission rates of tofacitinib, baricitinib, upadacitinib, and filgotinib compared with those of adalimumab were assessed in patients with rheumatoid arthritis (RA) who responded poorly to methotrexate (MTX). METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the Disease Activity Score in 28 joints with C‑reactive protein (DAS28-CRP), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and the Boolean remission of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients with inadequate responses to MTX. RESULTS: Four RCTs, comprising 3507 patients, met the inclusion criteria. The filgotinib 200 mg + MTX and upadacitinib 15 mg + MTX groups showed a significantly higher DAS28-CRP < 2.6 than adalimumab 40 mg + MTX. Upadacitinib 15 mg + MTX showed a significantly higher CDAI (≤ 2.8) than adalimumab 40 mg + MTX (odds ratio [OR]: 1.62; 95% credible interval [CrI]: 1.16-2.29). The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX had the highest probability of being the best treatment as it achieved a CDAI ≤ 2.8, followed by filgotinib 200 mg + MTX, baricitinib 4 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab 40 mg + MTX. The Boolean remission showed the same distribution pattern as that of the CDAI ≤ 2.8. Upadacitinib 15 mg + MTX showed a significantly higher SDAI ≤ 3.3 than adalimumab 40 mg + MTX (OR: 1.62; 95% CrI: 1.16-2.28). SUCRA ranking based on SDAI ≤ 3.3 indicated that upadacitinib 15 mg + MTX had the highest probability of being the best treatment for achieving an SDAI ≤ 3.3, followed by baricitinib 4 mg + MTX, filgotinib 200 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab 40 mg + MTX. CONCLUSIONS: In RA patients with an inadequate response to MTX, remission rates with JAK inhibitors were significantly higher; there is evidence for differences in efficacy regarding remission among the different JAK inhibitors.
Authors: Ernest Choy; Daniel Aletaha; Frank Behrens; Axel Finckh; Juan Gomez-Reino; Jacques-Eric Gottenberg; Florian Schuch; Andrea Rubbert-Roth Journal: Rheumatology (Oxford) Date: 2017-05-01 Impact factor: 7.580