Treatment with upadacitinib – monotherapy or in combination with methotrexate – inhibits structural joint damage progression in patients with rheumatoid arthritis (RA), according to study results published in Rheumatology.
Previous research has shown that upadacitinib reduces the progression of structural joint damage at 6 months when used alone or in combination with methotrexate in patients with active RA.
The objective of the current study was to determine the progression of structural joint damage over a period of 1 year in patients with moderately to severely active RA.
The study sample included 945 methotrexate-naive patients from the SELECT-EARLY trial (ClinicalTrials.gov Identifier: NCT02706873) who were randomly assigned to receive upadacitinib 15 or 30 mg once daily or methotrexate monotherapy; and 1629 methotrexate-inadequate responders from the SELECT-COMPARE trial (ClinicalTrials.gov Identifier: NCT02629159) who were randomly assigned to receive upadacitinib 15 mg once daily, adalimumab 40 mg every other week, or placebo, added to background methotrexate.
In both studies, the mean changes from baseline in van der Heijde modified Total Sharp Score (mTSS), joint-space narrowing score, and erosion score were determined at 6 months and 1 year.
In the SELECT-EARLY trial, treatment with upadacitinib was associated with inhibition of structural joint damage progression during 1 year, with mean changes from baseline in mTSS of 0.03, 0.14, and 1.00 for upadacitinib 15 mg, upadacitinib 30 mg, and methotrexate, respectively (P <.001 for both upadacitinib doses compared with methotrexate).
Treatment with upadacitinib was also associated with inhibition of structural joint damage progression over a 1-year period in the SELECT-COMPARE trial, with mean changes from baseline in mTSS of 0.28 for upadacitinib with methotrexate and 1.73 for placebo with methotrexate (P <.001). At 1 year, a significantly higher percentage of patients in the upadacitinib 15 mg group did not experience radiographic progression compared with the placebo group.
Significantly reduced progression of joint-space narrowing and erosion scores were observed at 1 year with upadacitinib 15 mg and methotrexate compared with placebo and methotrexate (-0.62 vs -0.66, respectively; P <.001).
In methotrexate-naive patients with RA, the number needed to treat to prevent 1 additional patient from developing erosion progression over that expected with methotrexate was 6.7 for upadacitinib 15 mg and 6.6 for upadacitinib 30 mg.
The study had several limitations, including that all patients receiving placebo in the SELECT-COMPARE trial were rescued or switched to upadacitinib by week 26, so there was no true placebo comparator group up to 1 year and that the placebo duration was limited to 6 months. In addition, the SELECT-COMPARE study was not planned or powered to compare upadacitinib with adalimumab for radiographic endpoints.
“Upadacitinib significantly inhibited the progression of structural joint damage through 1 year in patients with active RA who were at increased risk for joint damage both as monotherapy in methotrexate-naive patients and in combination with background methotrexate in methotrexate-[inadequate responder] patients,” the researchers concluded.
Disclosure: This study was supported by AbbVie. Please see the original reference for a full list of authors’ disclosures.
Peterfy CG, Strand V, Friedman A, et al. Inhibition of structural joint damage progression with upadacitinib in rheumatoid arthritis: 1-year outcomes from the SELECT phase 3 program. Rheumatology (Oxford). Published online December 13, 2021. doi:10.1093/rheumatology/keab861