Upadacitinib Demonstrates Efficacy in RA Treatment Regardless of Patient’s Baseline CRP Levels

Upadacitinib monotherapy or in combination with methotrexate (MTX) was effectively associated with causing disease remission or low disease activity (LDA) for patients with rheumatoid arthritis (RA), according to a recent study published in Clinical and Experimental Rheumatology.

Woman seated with rheumatoid arthritis | Image credit: Valentina - stock.adobe.com

At present, typical treatments for RA include conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). However, these drugs are less effective as a patient’s disease progresses, often necessitating the use of biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) such as Janus kinase (JAK) inhibitors to induce disease remission or LDA.

Even with the addition of these medications, not all patients exhibit adequate responses to DMARDs. In these cases, in Germany, the selective and reversible JAK inhibitor, upadacitinib, has demonstrated efficacy in the treatment of adults with moderate to severe RA who have not had success with one or more DMARDs.

The use of upadacitinib was reinforced by findings of the SELECT-NEXT phase 3 trial. In this study, upadacitinib brought about disease remission in patients regardless of their C-reactive protein (CRP) levels. As the authors of the present study note, CRP levels are typically an important marker of disease activity and clinical trials often enroll patients with elevated CRP levels, thereby excluding many who do not meet certain requirements. Expanding research on medications that are effective regardless of CRP levels, they add, can provide more opportunities for patients' ability to access care through trials or otherwise.

There is lacking real-world evidence on patients with active disease who do not have elevated CRP levels. To further the clinical understanding of these patients, researchers conducted a prospective, non-interventional, real-world study on whether upadacitinib’s effectiveness—as a mono or dual therapy with MTX (a csDMARD)—is influenced by baseline CRP levels in the treatment RA.

Data from 518 patients across 50 rheumatology outpatient clinics and office-based rheumatologists in Germany were enrolled between February 6, 2020, and February 1, 2022. They were subsequently assigned to receive either upadacitinib monotherapy (n = 260) or upadacitinib plus MTX (n = 273). Patients were administered 15 mg of upadacitinib once daily and were followed for up to 12 months.

The primary end point of this study was the achievement of clinical remission (Clinical Disease Activity Index [CDAI] ≤ 2.8). Secondary end points included Simple Disease Activity Index (SDAI) scores ≤ 3.3, 28-joint Disease Activity Scale (DAS28) for CRP (DAS28-CRP) or erythrocyte sedimentation rate (ESR; DAS28-ESR) scores below 2.6, or reaching a state of LDA (CDAI ≤ 10 or SDAI ≤ 11; DAS28-CRP ≤ 3.2 or DAS28-ESR ≤ 3.2).

Patients who completed more than 1 follow-up were classified as the intent-to-treat (ITT) population (n = 431). At 6 months, 24.4% (105) of the total ITT cohort reached clinical remission. The treatment groups with upadacitinib monotherapy and dual therapy with MTX exhibited similar rates of remission (23.2% [48/207] and 25.4% [57/224], respectively). At 12 months, the total proportion of patients reaching remission according to CDAI, SDAI, and DAS28-CRP criteria was 28.3% (105), 34.5% (128) and 66.3% (246). In these measures, patient achievements for LAD at 12 months reached rates of 77.4% (287), 76.5% (284), and 81.7% (303). These trends were similar in both treatment groups receiving upadacitinib and baseline CRP levels were not significantly associated with an individual’s likelihood of achieving remission. Additionally, many patients reported improvements in experienced pain and fatigue by the end of the trial period.

The effects of upadacitinib were comparable in the monotherapy and combination therapy groups, regardless of a patient’s prior experience and response to bDMARDs. The findings demonstrate the effectiveness of upadacitinib therapy in the treatment of RA, inducement of clinical remission, and bolster evidence suggesting that baseline CRP levels may not correlate with a patient’s disease activity or potential response to treatment.

Reference

Witte T, Kiltz U, Haas F, et al. The impact of C-reactive protein levels on the effectiveness of upadacitinib in patients with rheumatoid arthritis: a 12-month prospective, non-interventional German study. Clin Exp Rheumatol. Published online November 15, 2023. doi:10.55563/clinexprheumatol/11255h