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- Aldridge, Jonathan, et al.
(författare)
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Blood chemokine levels are markers of disease activity but not predictors of remission in early rheumatoid arthritis.
- 2022
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Ingår i: Clinical and experimental rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 40:7, s. 1393-1402
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Tidskriftsartikel (refereegranskat)abstract
- In early rheumatoid arthritis (eRA) plasma levels of specific chemokines have been shown to correlate with disease activity. However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels in patients with untreated eRA.This study included 347 Swedish patients with untreated eRA from the larger NORD-STAR randomised treatment trial. Here, eRA patients were treated with methotrexate combined with either prednisolone, anti-TNF (certolizumab-pegol), CTLA-4Ig (abatacept) or anti-IL6 receptor (tocilizumab). The primary clinical outcome was remission by clinical disease activity index (CDAI) defined as CDAI ≤ 2.8. Disease activity was assessed by CDAI, DAS28-ESR, DAS28-CRP, swollen joint counts, tender joint counts, ESR and CRP. The plasma concentrations of 14 chemokines were measured at baseline and after 24 weeks of treatment by bead-based immunoassay or ELISA.Baseline plasma concentrations of CXCL10, CXCL8, CXCL9, CXCL11, CXCL5 and CCL2 correlated with baseline disease activity measures. After 24 weeks of treatment, plasma levels of CXCL10, CXCL8, CXCL9, CXCL11 and CXCL13 decreased in all treatment groups except in patients treated with anti-IL6 receptor. In multivariate factor analysis, plasma chemokine levels at baseline could not differentiate patients who attained remission by week 24 from those who did not in any of the treatment groups.In patients with untreated eRA, plasma levels of several chemokines correlate with disease activity at baseline but cannot predict remission after 24 weeks of treatment with methotrexate combined with prednisolone, anti‑TNF, CTLA‑4Ig or anti‑IL6R.
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| 2. |
- Lend, Kristina, et al.
(författare)
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Methotrexate safety and efficacy in combination therapies in patients with early rheumatoid arthritis: a post-hoc analysis of a randomized controlled trial (NORD-STAR).
- 2024
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Ingår i: Arthritis & rheumatology (Hoboken, N.J.). - 2326-5205. ; 76:3, s. 363-376
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Tidskriftsartikel (refereegranskat)abstract
- To investigate methotrexate safety and influence of dose on efficacy outcomes in combination with three different biological treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA).This post-hoc analysis included 812 treatment-naïve early RA patients who were randomized (1:1:1:1) in the NORD-STAR trial (NCT01491815) to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab. Methotrexate safety, doses, and dose effects on Clinical Disease Activity Index (CDAI) remission were assessed after 24weeks of treatment.Compared with ACT, the prevalence of methotrexate-associated side effects was higher when methotrexate was combined with tocilizumab (HR 1.48 [95% CI 1.20 to 1.84]), but not with certolizumab-pegol (HR 0.99 [0.79 to 1.23]) or with abatacept (HR 0.93 [0.75 to 1.16]). With ACT as the reference, methotrexate dose was significantly lower when used in combination with tocilizumab (β -4.65 [95% CI -5.83 to -3.46], p<0.001), with abatacept (β -1.15 [-2.27 to -0.03], p=0.04), and numerically lower in combination with certolizumab-pegol (β -1.07 [-2.21 to 0.07], p=0.07). Methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the treatment combinations.Methotrexate was generally well tolerated in combination therapies, but adverse events were a limiting factor in receiving the target dose of 25 mg/week, and these were more frequent in combination with tocilizumab versus active conventional treatment. On the other hand, methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the four treatment combinations at 24weeks.
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