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The investigational oral Janus kinase (JAK) inhibitor upadacitinib has shown promise as a monotherapy treatment option for patients with active rheumatoid arthritis despite treatment with methotrexate, based on results from the phase 3 SELECT-MONOTHERAPY trial.
“The SELECT-MONOTHERAPY trial showed that patients who were having an inadequate response to methotrexate could be switched to oral upadacitinib monotherapy (15 mg or 30 mg) once a day, with improvements in clinical signs and symptoms, physical function, and quality of life measures, compared with patients who continued on their previous methotrexate dose,” Josef S. Smolen, MD, of the Medical University of Vienna, and his colleagues wrote in the Lancet.
The phase 3, double-blind, placebo-controlled trial randomized 648 RA patients with active disease despite methotrexate therapy from 138 sites in 24 countries.
Higher proportions of patients receiving upadacitinib 15 mg and 30 mg versus continued methotrexate achieved the primary endpoints of the proportion of patients achieving a 20% improvement in American College of Rheumatology (ACR 20) criteria at 14 weeks and the proportion achieving low disease activity defined as a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or lower.
An ACR 20 response was achieved by 89 (41%) of 216 patients (95% confidence interval, 35%-48%) in the continued methotrexate group, 147 (68%) of 217 patients (95% CI, 62%-74%) receiving upadacitinib 15 mg, and 153 (71%) of 215 patients (95% CI, 65%-77%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).
A DAS28-CRP score of 3.2 or lower was met by 42 (19%) of 216 (95% CI, 14%-25%) receiving methotrexate, 97 (45%) of 217 (95% CI, 38%-51%) receiving upadacitinib 15 mg, and 114 (53%) of 215 (95% CI, 46%-60%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).
The investigators noted that responses were observed with both 15-mg and 30-mg doses of upadacitinib, although numerically higher responses were seen with the 30-mg dose.
“Whether the 15-mg or the 30-mg dose is the more appropriate one for patients who switch from methotrexate to upadacitinib will have to be established in conjunction with data from the other phase 3 upadacitinib trials,” they wrote.
Treatment-emergent adverse events were reported at similar frequencies across the arms (n = 102 with methotrexate; n = 103 with upadacitinib 15 mg; n = 105 with upadacitinib 30 mg).
Serious adverse events were reported in 11 (5%) of 217 patients in the upadacitinib 15 mg arm, 6 (3%) of 216 patients in the continued methotrexate arm, and 6 (3%) of 215 patients in the upadacitinib 30 mg arm.
“This favorable benefit-risk profile of upadacitinib monotherapy has the potential to provide a treatment option for patients who are intolerant to methotrexate or who prefer a treatment without the need for concomitant [conventional synthetic] DMARDs,” the authors wrote.
The study was funded by AbbVie. Dr. Smolen and most authors reported financial ties to AbbVie and other companies marketing rheumatoid arthritis treatments. Five authors are employees of AbbVie.
SOURCE: Smolen JS et al. Lancet. 2019;393[10188]:2303-11. doi: 10.1016/S0140-6736(19)30419-2
Treatment recommendations for the management of RA do not currently include the use of novel disease-modifying antirheumatic drugs (DMARDs) as monotherapy. However, there is growing interest in this concept, most likely because of poor tolerability and contraindications to conventional synthetic DMARDs such as methotrexate.
The observed treatment effects of SELECT-NEXT and the current trial by Prof. Smolen and associates are similar for both control groups (responders: 36% vs. 41% on methotrexate plus placebo) and for the upadacitinib treatment groups, regardless of concomitant methotrexate status (64% on methotrexate plus upadacitinib 15 mg or 66% on methotrexate plus upadacitinib 30 mg vs. 68% on upadacitinib 15 mg or 71% on upadacitinib 30 mg).
Prof. Smolen and associates chose a trial design that assessed the continuation of methotrexate plus placebo versus switching from methotrexate to upadacitinib monotherapy, but does this research question adequately reflect the question often raised in clinical practice: Should a novel DMARD be added to methotrexate or should patients switch from methotrexate to a novel DMARD?
But we now need a trial that compares a switch versus an add-on strategy to adequately answer the question on the treatment of resistant RA.
These comments are adapted from an accompanying editorial by Anna Moltó, MD, and Maxime Dougados, MD, both with the rheumatology department at Cochin Hospital, Paris (Lancet. 2019;393[10188]:2277-8. doi: 10.1016/S0140-6736(19)30768-8). The rheumatology department at Cochin Hospital has received grants to do clinical studies and trials from AbbVie and other manufacturers of drugs for RA. Both Dr. Dougados and Dr. Moltó reported receiving personal fees for advisory boards and symposia from AbbVie and other manufacturers of drugs for RA outside the area of work commented on here.
Treatment recommendations for the management of RA do not currently include the use of novel disease-modifying antirheumatic drugs (DMARDs) as monotherapy. However, there is growing interest in this concept, most likely because of poor tolerability and contraindications to conventional synthetic DMARDs such as methotrexate.
The observed treatment effects of SELECT-NEXT and the current trial by Prof. Smolen and associates are similar for both control groups (responders: 36% vs. 41% on methotrexate plus placebo) and for the upadacitinib treatment groups, regardless of concomitant methotrexate status (64% on methotrexate plus upadacitinib 15 mg or 66% on methotrexate plus upadacitinib 30 mg vs. 68% on upadacitinib 15 mg or 71% on upadacitinib 30 mg).
Prof. Smolen and associates chose a trial design that assessed the continuation of methotrexate plus placebo versus switching from methotrexate to upadacitinib monotherapy, but does this research question adequately reflect the question often raised in clinical practice: Should a novel DMARD be added to methotrexate or should patients switch from methotrexate to a novel DMARD?
But we now need a trial that compares a switch versus an add-on strategy to adequately answer the question on the treatment of resistant RA.
These comments are adapted from an accompanying editorial by Anna Moltó, MD, and Maxime Dougados, MD, both with the rheumatology department at Cochin Hospital, Paris (Lancet. 2019;393[10188]:2277-8. doi: 10.1016/S0140-6736(19)30768-8). The rheumatology department at Cochin Hospital has received grants to do clinical studies and trials from AbbVie and other manufacturers of drugs for RA. Both Dr. Dougados and Dr. Moltó reported receiving personal fees for advisory boards and symposia from AbbVie and other manufacturers of drugs for RA outside the area of work commented on here.
Treatment recommendations for the management of RA do not currently include the use of novel disease-modifying antirheumatic drugs (DMARDs) as monotherapy. However, there is growing interest in this concept, most likely because of poor tolerability and contraindications to conventional synthetic DMARDs such as methotrexate.
The observed treatment effects of SELECT-NEXT and the current trial by Prof. Smolen and associates are similar for both control groups (responders: 36% vs. 41% on methotrexate plus placebo) and for the upadacitinib treatment groups, regardless of concomitant methotrexate status (64% on methotrexate plus upadacitinib 15 mg or 66% on methotrexate plus upadacitinib 30 mg vs. 68% on upadacitinib 15 mg or 71% on upadacitinib 30 mg).
Prof. Smolen and associates chose a trial design that assessed the continuation of methotrexate plus placebo versus switching from methotrexate to upadacitinib monotherapy, but does this research question adequately reflect the question often raised in clinical practice: Should a novel DMARD be added to methotrexate or should patients switch from methotrexate to a novel DMARD?
But we now need a trial that compares a switch versus an add-on strategy to adequately answer the question on the treatment of resistant RA.
These comments are adapted from an accompanying editorial by Anna Moltó, MD, and Maxime Dougados, MD, both with the rheumatology department at Cochin Hospital, Paris (Lancet. 2019;393[10188]:2277-8. doi: 10.1016/S0140-6736(19)30768-8). The rheumatology department at Cochin Hospital has received grants to do clinical studies and trials from AbbVie and other manufacturers of drugs for RA. Both Dr. Dougados and Dr. Moltó reported receiving personal fees for advisory boards and symposia from AbbVie and other manufacturers of drugs for RA outside the area of work commented on here.
The investigational oral Janus kinase (JAK) inhibitor upadacitinib has shown promise as a monotherapy treatment option for patients with active rheumatoid arthritis despite treatment with methotrexate, based on results from the phase 3 SELECT-MONOTHERAPY trial.
“The SELECT-MONOTHERAPY trial showed that patients who were having an inadequate response to methotrexate could be switched to oral upadacitinib monotherapy (15 mg or 30 mg) once a day, with improvements in clinical signs and symptoms, physical function, and quality of life measures, compared with patients who continued on their previous methotrexate dose,” Josef S. Smolen, MD, of the Medical University of Vienna, and his colleagues wrote in the Lancet.
The phase 3, double-blind, placebo-controlled trial randomized 648 RA patients with active disease despite methotrexate therapy from 138 sites in 24 countries.
Higher proportions of patients receiving upadacitinib 15 mg and 30 mg versus continued methotrexate achieved the primary endpoints of the proportion of patients achieving a 20% improvement in American College of Rheumatology (ACR 20) criteria at 14 weeks and the proportion achieving low disease activity defined as a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or lower.
An ACR 20 response was achieved by 89 (41%) of 216 patients (95% confidence interval, 35%-48%) in the continued methotrexate group, 147 (68%) of 217 patients (95% CI, 62%-74%) receiving upadacitinib 15 mg, and 153 (71%) of 215 patients (95% CI, 65%-77%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).
A DAS28-CRP score of 3.2 or lower was met by 42 (19%) of 216 (95% CI, 14%-25%) receiving methotrexate, 97 (45%) of 217 (95% CI, 38%-51%) receiving upadacitinib 15 mg, and 114 (53%) of 215 (95% CI, 46%-60%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).
The investigators noted that responses were observed with both 15-mg and 30-mg doses of upadacitinib, although numerically higher responses were seen with the 30-mg dose.
“Whether the 15-mg or the 30-mg dose is the more appropriate one for patients who switch from methotrexate to upadacitinib will have to be established in conjunction with data from the other phase 3 upadacitinib trials,” they wrote.
Treatment-emergent adverse events were reported at similar frequencies across the arms (n = 102 with methotrexate; n = 103 with upadacitinib 15 mg; n = 105 with upadacitinib 30 mg).
Serious adverse events were reported in 11 (5%) of 217 patients in the upadacitinib 15 mg arm, 6 (3%) of 216 patients in the continued methotrexate arm, and 6 (3%) of 215 patients in the upadacitinib 30 mg arm.
“This favorable benefit-risk profile of upadacitinib monotherapy has the potential to provide a treatment option for patients who are intolerant to methotrexate or who prefer a treatment without the need for concomitant [conventional synthetic] DMARDs,” the authors wrote.
The study was funded by AbbVie. Dr. Smolen and most authors reported financial ties to AbbVie and other companies marketing rheumatoid arthritis treatments. Five authors are employees of AbbVie.
SOURCE: Smolen JS et al. Lancet. 2019;393[10188]:2303-11. doi: 10.1016/S0140-6736(19)30419-2
The investigational oral Janus kinase (JAK) inhibitor upadacitinib has shown promise as a monotherapy treatment option for patients with active rheumatoid arthritis despite treatment with methotrexate, based on results from the phase 3 SELECT-MONOTHERAPY trial.
“The SELECT-MONOTHERAPY trial showed that patients who were having an inadequate response to methotrexate could be switched to oral upadacitinib monotherapy (15 mg or 30 mg) once a day, with improvements in clinical signs and symptoms, physical function, and quality of life measures, compared with patients who continued on their previous methotrexate dose,” Josef S. Smolen, MD, of the Medical University of Vienna, and his colleagues wrote in the Lancet.
The phase 3, double-blind, placebo-controlled trial randomized 648 RA patients with active disease despite methotrexate therapy from 138 sites in 24 countries.
Higher proportions of patients receiving upadacitinib 15 mg and 30 mg versus continued methotrexate achieved the primary endpoints of the proportion of patients achieving a 20% improvement in American College of Rheumatology (ACR 20) criteria at 14 weeks and the proportion achieving low disease activity defined as a 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) of 3.2 or lower.
An ACR 20 response was achieved by 89 (41%) of 216 patients (95% confidence interval, 35%-48%) in the continued methotrexate group, 147 (68%) of 217 patients (95% CI, 62%-74%) receiving upadacitinib 15 mg, and 153 (71%) of 215 patients (95% CI, 65%-77%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).
A DAS28-CRP score of 3.2 or lower was met by 42 (19%) of 216 (95% CI, 14%-25%) receiving methotrexate, 97 (45%) of 217 (95% CI, 38%-51%) receiving upadacitinib 15 mg, and 114 (53%) of 215 (95% CI, 46%-60%) receiving upadacitinib 30 mg (P less than .0001 for both doses vs. continued methotrexate).
The investigators noted that responses were observed with both 15-mg and 30-mg doses of upadacitinib, although numerically higher responses were seen with the 30-mg dose.
“Whether the 15-mg or the 30-mg dose is the more appropriate one for patients who switch from methotrexate to upadacitinib will have to be established in conjunction with data from the other phase 3 upadacitinib trials,” they wrote.
Treatment-emergent adverse events were reported at similar frequencies across the arms (n = 102 with methotrexate; n = 103 with upadacitinib 15 mg; n = 105 with upadacitinib 30 mg).
Serious adverse events were reported in 11 (5%) of 217 patients in the upadacitinib 15 mg arm, 6 (3%) of 216 patients in the continued methotrexate arm, and 6 (3%) of 215 patients in the upadacitinib 30 mg arm.
“This favorable benefit-risk profile of upadacitinib monotherapy has the potential to provide a treatment option for patients who are intolerant to methotrexate or who prefer a treatment without the need for concomitant [conventional synthetic] DMARDs,” the authors wrote.
The study was funded by AbbVie. Dr. Smolen and most authors reported financial ties to AbbVie and other companies marketing rheumatoid arthritis treatments. Five authors are employees of AbbVie.
SOURCE: Smolen JS et al. Lancet. 2019;393[10188]:2303-11. doi: 10.1016/S0140-6736(19)30419-2
FROM THE LANCET