Long-term upadacitinib superior to methotrexate for rheumatoid arthritis
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Key takeaways:
- Patients with RA treated with first-line upadacitinib over 5 years had greater reductions in disease activity vs. methotrexate.
- Upadacitinib’s overall risk-benefit profile was superior to methotrexate.
Upadacitinib shows superior clinical, radiographic and patient-reported outcomes in RA, and has a more favorable risk-benefit profile, compared with methotrexate over 5 years, according to data published in Arthritis Research & Therapy.
“For the clinician, first-line use of upadacitinib is not supported by regulatory approvals or expert recommendations,” Ronald F. van Vollenhoven, MD, PhD, chair of the department of rheumatology and clinical immunology at the Amsterdam Medical Center, told Healio. “However, the clinician who prescribes this medication in established RA may find additional comfort in knowing it is effective in that setting as well.”
To assess the 5-year efficacy and safety of upadacitinib (Rinvoq, Abbvie), vs. methotrexate, as a first-line therapy in moderate-to-severe RA, van Vollenhoven and colleagues conducted a long-term extension of the phase 3 SELECT-EARLY trial. In that trial, participants with RA were either naïve to methotrexate or had received three or fewer weekly doses, with a 4-week washout period required before beginning upadacitinib.
Among the 945 patients who completed the original trial, 775 (82%) entered the long-term extension. The 260-week extension was completed by 23 patients treated with weekly methotrexate — titrated to 20 mg by week 8 — while 11 were treated with daily upadacitinib 15 mg and three received daily upadacitinib 30 mg.
According to the researchers, Clinical Disease Activity Index remission at 260 weeks was achieved by 53% of patients in the upadacitinib 15 mg group, and in 59% of the upadacitinib 30 mg group, compared with 43% in the methotrexate group. In non-responder imputation analyses, upadacitinib also demonstrated better responses vs. methotrexate on CDAI, DAS28 score based on C-reactive protein, and ACR20/50/70 (nominal P < .001 for all).
Regarding safety, the upadacitinib 30 mg group saw numerically higher rates of most treatment-emergent adverse events, serious adverse events and other adverse events that led to discontinuation. Compared with methotrexate, both upadacitinib groups also experienced numerically higher rates of serious infections, herpes zoster, creatine phosphokinase elevation, nonmelanoma skin cancer and neutropenia.
Van Vollenhoven noted that while he was “personally surprised” by the magnitude of differences between upadacitinib and methotrexate in the initial study, the long-term extension results were more expected.
“The fact that continued treatment with upadacitinib showed maintained benefits did not surprise me a lot,” he said. “The mechanism of this drug would be expected to apply even long-term.
“It is clear that in the current climate, regulatory authorities are not quite ready to approve any JAK inhibitors as first-line therapy for RA, and, likewise, organizations such as EULAR and the American College of Rheumatology have stood by the first line of treatment being methotrexate, or conventional DMARDs in general,” van Vollenhoven added. “I personally believe that this question should be viewed more open-mindedly and that patients in some instances should be allowed to benefit from the greater efficacy of modern treatments.”
For more information:
Ronald F. van Vollenhoven, MD, PhD, can be reached at r.vanvollenhoven@amsterdamumc.nl.
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