Obiekt
Tytuł: Biological disease-modifying anti-rheumatic drugs with a focus on rituximab in achieving remission and low disease activity in patients with rheumatoid arthritis and psoriatic arthritis
Abstrakt:
Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are the two most common chronic rheumatic inflammatory diseases. Biological disease-modifying drugs (bDMARDs), initially the original ones, and then also their biosimilar equivalents significantly increased the number of patients with RA and PsA achieving both remission and low disease activity. It was observed that the effects of bDMARDs in the so-called real-world evidence (RWE) differ from those recorded in randomized clinical trials, so there is a need to acquire and analyze RWE data. Data from long-term observations of patients treated in RWE are relatively scarce, both in relation to bDMARDs in PsA and to some bDMARDs, especially rituximab (RTX), in RA. So far, no RWE data on the effectiveness of biosimilar RTX, GP2013 in RA have been published. Moreover, the methods of defining remission and low disease activity in both RA and PsA remains an important and unresolved problem. Since no uniform and universally accepted definition of these concepts has been adopted, the percentage of patients achieving remission and low disease activity remains dependent on the indicators used, and therefore the discrepancies reported in the literature are significant. The aim of this study was: 1. to explore drug effectiveness, drug survival and reasons for discontinuing therapy for RTX and its biosimilar, GP2013, in pat ; ients with RA treated in RWE; 2. to explore for the impact of different remission definitions on the number of patients with PsA achieving remission and/or low disease activity in RWE; 3. to explore for the impact of bDMARDs use on long-term changes in PsA activity and the number of patients achieving remission or low disease activity, with a focus on potentially sex-related differences. Materials and methods The study was conducted based on data from adult patients with RA or PsA collected in the register of the Sørlandet Hospital in Krisitansand, Norway, between the year 2006 and 2020. In the first part of the study, the analysis included patients with RA treated with RTX (n = 249) or its biosimilar, GP2013 (n = 110). Drug effectiveness was assessed by changes in inflammatory markers, disease activity composite scores and the proportion of patients achieving remission or low disease activity according to the DAS28 criteria and with a good and/or moderate response to treatment according to the EULAR criteria. Baseline predictors of drug effectiveness were analyzed with linear and logistic regression models. Drug survival was assessed with Kaplan-Meier analysis, baseline variables associated with drug survival with multivariable Cox proportional hazard models. In the second part of the study, PsA patients with only peripheral or peripheral and axial involvement ; (n = 114) treated with various bDMARDs were included. To explore for the impact of different remission definitions on the number of PsA patients achieving remission and/or low disease activity, the following composite scores were analyzed: clinical disease activity index (CDAI), simplified disease activity index (SDAI), disease activity index for psoriatic arthritis (DAPSA), clinical DAPSA (cDAPSA), DAS28, very low disease activity (VLDA), and minimal disease activity (MDA). To assess sex-related differences, both entire cohort and men and women subgroups were analyzed. Baseline variables associated with remission were examined using linear and logistic regression models. P-value < 0.05 was considered significant. Results In RA patients treated with RTX, all analyzed disease activity scores and patientreported outcomes (PROs), improved significantly (p < 0.01) during the 5-year follow-up compared to baseline. The most substantial changes were observed in the second year of treatment and effect was maintained throughout the entire analyzed period, with DAS28 4.9 at baseline, 4.7 after 1 year, 3.6 after 2 years, 3.1 after 3 years, 2 after 4 years, 8, after 5 years 2.7. No significant differences in drug effectiveness were noted between patients naïve to and previously treated with bDMARDs, and between concomitant and non-concomitant users of conventional syntheti ; c DMARDs (csDMARDs). Drug survival was 83% after 1 year, 66% after 2 years, 53% after 3 years, 46% after 4 years and 34% after 5 years of follow-up. No significant differences in drug survival between concomitant and non-concomitant users of csDMARDs (p = 0.47), in patients naïve to and previously exposed to bDMARDs (p = 0.25) were observed. Significantly better drug survival was noted in patients with positive rheumatoid factor (RF, p < 0.01). RF-seropositivity was also independently associated with a better drug survival in Cox regression analysis (hazard ratio 0.561). The most common reason for drug discontinuation was physician's decision (36.2%), followed by lack or loss of treatment efficacy (19.2%). Among 110 RA patients treated with biosimilar RTX, GP2013, 88 underwent mandatory non-medical switch and 22 naive to RTX started treatment with GP2013. All analyzed disease activity indices were initially significantly higher in patients starting treatment from GP2013. In this subgroup, after 1 year of treatment, improvement in all disease activity scores and PROs was observed and maintained after 2 years of follow-up. Changes were statistically significant for erythrocyte sedimentation rate (ESR, p = 0.004), number of swollen (SJC28, p = 0.043) and tender joint counts (TJC28, p = 0.001), DAS28-ESR (p = 0.014), DAS28 calculated with c-reactive protein (DAS28-CR ; P, p = 0.002), and CDAI (0.010). In the subgroup continuing therapy with GP2013, the treatment effect was maintained for all analyzed disease activity scores, except PROs. For the total cohort, GP2013 drug survival was 80.0% after 1 year and 57.7% after 2 years of follow-up, while in the subgroup undergone mandatory non-medical switch, 84.1% after 1 year and 60.2% after 2 years which was significantly higher than in the subgroup treated with GP2013 “de novo” (63.6% and 49.0% after 1 and 2 years of follow-up, respectively; p = 0.036). In the total cohort and in patients continuing therapy with GP2013, the most common reason for discontinuation was remission (38.6% and 40.3%, respectively), followed by physician's decision (27.1% and 27.4%, respectively). In the second part of the study, among 114 PsA patients, 37.7% were using bDMARDs (97.7% tumor necrosis factor inhibitor, TNFi and 2.3% interleukin-12/23 inhibitor, IL-12/23i, ustekinumab). During the 5-year follow-up, the number of patients treated with bDMARDs increased from 37.7% to 46.5% and this was statistically significant (p = 0.018). After 5 years, 77.4% (n = 41) patients treated with bDMARDs were using TNFi, 18.9% (n = 10) interleukin- 17A inhibitor (interleukin-17A inhibitor, IL-17Ai, secukinumab), 1.9% (n = 1) IL-12/23i (ustekinumab) and 1.9% (n = 1) RTX. At baseline, the highest remission rates were r ; ecorded for DAS28-CRP (44.7%), followed by DAS28-ESR (33.3%), SDAI (21.9%), CDAI (19.3%), cDAPSA (14.9 %) and DAPSA (13.2%) Only 2.6% of patients achieved remission defined according to the Boolean criteria, 25.4% achieved MDA and 4.4% VLDA. After 5 years, the proportion of patients achieving remission increased significantly for DAS28-CRP (+11.1%, p = 0.033), DAS28-ESR (+21.2%, p < 0.001), CDAI (+9.7%, p = 0.034) and cDAPSA (+7.6%, p = 0.028). Non-significant increases were observed for SDAI, DAPSA, Boolean remission and MDA/VLDA. Both at baseline and after 5-year follow-up, more men than women were treated with bDMARDs and these differences were statistically significant (baseline: p = 0.048, followup: p = 0.008). Women scored higher on generalized pain, joint pain and fatigue, had higher numbers of tender joints and enthesitis scores, higher DAPSA, cDAPSA, SDAI, CDAI, DAS28-ESR, DAS28-CRP and significantly higher number of comorbidities both at baseline and at follow-up. Conclusions 1. In RA patients treated with RTX in monotherapy (without concomitant use of csDMARDs), no differences in neither drug effectiveness nor drug survival were observed, comparing to concomitant users of csDMARDs. Previous use of bDMARDs other than RTX did not affect drug effectiveness and drug survival. A significant response to RTX treatment was observed mainly in the second year ; of therapy, and RF, but not ACPA seropositivity was independently associated with a better drug survival. 2. In RA patients undergoing mandatory non-medical switch from originator RTX to its biosimilar GP2013, no deterioration in disease activity in the 2-year follow-up period was observed. In RA patients starting treatment with GP2013, treatment response was satisfactory, and effect remained stable after 2 years. GP2013 drug survival was comparable to data published for RTX. 3. In PsA patients with only peripheral or peripheral with axial involvement observed in 2013- 2020 period, improvement in treatment outcomes and increase in the proportion of patients achieving remission/low disease activity was noted, which is most likely related to more intensified treatment with bDMARDs and access to bDMARDs with new modes of action in addition to TNFi. Women had higher PROs and disease activity indices, were less likely to be treated with bDMARDs and seemed to be less likely to achieve remission/low disease activity than men. The proportion of PsA patients achieving remission/low disease activity varied significantly depending on remission definition used, ranging from 10% to 70%. Such a large variability of results with significant implications in everyday clinical practice, may suggest the need to verify methods currently used for assessing remission and low disease ; activity.
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Instytucja nadająca tytuł:
Rada Dyscypliny Nauki medyczne
Promotor:
Korkosz, Mariusz ; Haugeberg, Glenn
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Data ostatniej modyfikacji:
16 lip 2024
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16 lip 2024
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| Nazwa wydania | Data |
|---|---|
| UJCM5abc991d9a154208a911978510a43c58 | 16 lip 2024 |
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