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- Barbulescu, A, et al.
(författare)
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COMPARATIVE EFFECTIVENESS OF JAKI VERSUS BDMARDS; A NATIONWIDE STUDY IN RA
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 68-68
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The Janus kinase inhibitors (JAKi) have been increasingly used for the treatment of rheumatoid arthritis (RA) in Sweden, with baricitinib representing ~80% of prescriptions. Evidence regarding the comparative effectiveness of JAKis versus biologics (bDMARDs), and in particular non- tumour-necrosis-factor inhibitor (TNFi) bDMARDs, in real-life is limited.Objectives:To compare RA patients treated with bDMARDs and JAKi in Sweden, in terms of: (1) patient characteristics at treatment start; (2) proportions of patients remaining on therapy, and response rates, at 12 months.Methods:RA patients starting treatment in 2017 and 2018 with either a TNFi, rituximab, abatacept, interleukin 6 inhibitors (IL6i) or a JAKi as different lines of treatment were identified in the Swedish Rheumatology Quality Register. One patient could contribute with more than one treatment episode.Treatment response at 12 months was measured as EULAR good response, HAQ improvement >0.2 units, DAS28 and CDAI remission, and as 0 tender and swollen joint counts (28JC). Patients were classified as non-responders if they stopped treatment before evaluation due to safety or inefficacy. Responses for patients who stopped treatment due to pregnancy or death and patients on treatment but with missing response were imputed using multiple imputation.Proportions of responders and differences in proportions between treatment groups, adjusted using inverse probability of treatment weighting, were estimated using linear regression with robust standard errors.Results:JAKi were often used after bDMARDs, and less frequently prescribed in combination with methotrexate. Measured comorbidities were less frequent among JAKi initiators than among non-TNFi biologic initiators, but RA activity was similar (Table).Table 1.Patient characteristics at treatment initiationCharacteristicMedian (IQR) or N (%)AbataceptIL6iRituximabTNFiJAKiTreatment Starts6945346923497905Age63 (53-71)59 (48-70)65 (54-73)59 (47-68)60 (51-70)Female543 (78)441 (83)519 (75)2739 (78)759 (84)RA duration (years)13 (5-21)10 (5-18)12 (6-22)9 (3-17)13 (7-22)Rheum. factor535 (79)385 (73)588 (87)2405 (70)686 (77)DAS284.8 (3.9-5.6)4.9 (4.0-5.7)4.7 (3.8-5.5)4.4 (3.4-5.3)4.7 (3.9-5.7)HAQ1.3 (0.8-1.6)1.3 (0.8-1.8)1.3 (0.8-1.8)1.0 (0.5-1.4)1.3 (0.8-1.8)Tender joints5 (2-9)6 (3-10)5 (2-9)4 (2-8)6 (2-10)Swollen joints4 (2-6)4 (2-7)4 (2-7)3 (1-6)4 (2-7)ts/bDMARD line3 (2-4)3 (2-4)2 (1-4)1 (1-2)4 (2-6)At least one prev. TNFi539 (78)442 (83)457 (66)1448 (41)770 (85)At least one prev. non-TNFi271 (39)220 (41)243 (35)441 (13)584 (65)Methotrexate co-treatment264 (50)172 (40)286 (53)1708 (62)296 (40)Glucocorticoids co-treatment247 (47)186 (43)275 (51)1126 (41)389 (53)Cancer*90 (2.8)64 (2.3)363 (7.7)410 (1.8)20 (2.2)Cardio-vascular dis.*245 (7.5)123 (4.4)322 (6.8)749 (3.4)41 (4.4)Chronic respiratory dis.*303 (9.3)140 (5.0)473 (10.0)721 (3.2)50 (5.4)Diabetes*324 (9.9)216 (7.7)456 (9.7)1479 (6.7)69 (7.5)* any diagnosis within 5 years before start Adjusted differences in proportion with each response outcomeIn a crude comparison, 65% (61%-68%) of JAKi, 62% (59%-66%) of abatacept, 58% (53%-62%) of IL6i, 80% (77%-83%) of rituximab and 68% (67%-70%) of TNFi initiators remained on treatment at 12 months after start. Also, JAKi showed lower overall responder proportions than TNFi, rituximab and IL6i.After adjustment for demographic and socio-economic factors, RA disease activity, previous use of ts/bDMARDs, co-medication with glucocorticoids and methotrexate and comorbidities at baseline, no significant differences in responder proportions between JAKi and bDMARDs remained (Figure). Furthermore, the adjusted proportions of patients on treatment were higher for JAKi and rituximab than for the other bDMARDs.Conclusion:This preliminary analysis of patients treated in clinical practice found no statistically significant difference in effectiveness between JAKi and bDMARDs.Disclosure of Interests:Andrei Barbulescu: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. These entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system, Katerina Chatzidionysiou Speakers bureau: Eli Lilly, Abbvie and Pfizer, Consultant of: Eli Lilly, Abbvie and Pfizer, Helena Forsblad-d’Elia: None declared, Alf Kastbom Employee of: Sanofi, Ulf Lindström: None declared, Carl Turesson Speakers bureau: Abbvie, Bristol-Myers Squibb, Medac, Pfizer, Roche, Consultant of: Roche, Grant/research support from: Bristol-Myers Squibb, Thomas Frisell: None declared
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| 3. |
- Barbulescu, A, et al.
(författare)
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Glucocorticoid exposure and the risk of serious infections in rheumatoid arthritis: a marginal structural model application
- 2023
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 62:10, s. 3391-3399
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveObservational studies have reported an increased risk of infections associated with glucocorticoids in RA, not supported by evidence from randomized controlled trials. Inappropriately accommodating time-varying exposure and confounding in observational studies might explain the conflicting results. Therefore, we compared the incidence of serious infections between different oral glucocorticoid dose patterns over three years in a prospective inception cohort, adjusting for time-varying confounders in marginal structural models.MethodsWe included 9654 newly diagnosed RA patients from the Swedish Rheumatology Quality Register between 2007–2018 and followed them for three years after the first rheumatology visit. Follow-up was divided into 90-day periods. A mean oral prednisone daily dose was calculated for each period and categorized into ‘no use’, ‘low’ (≤10 mg/day) and ‘high’ (>10 mg/day) doses. The incidence of serious infections (hospitalization for infection) over follow-up periods was modelled by pooled logistic regression allowing separate effects for recent and past exposure.ResultsAn increased incidence of serious infections was associated with higher compared with lower doses and with more recent compared with past glucocorticoid exposure. Over 3 years of follow-up, the marginal structural models predicted one additional serious infection for every 83 individuals treated with low GC doses for the first 6 months, and for every 125 individuals treated with high GC doses for the first 3 months, compared with no GC use.ConclusionOur results broadly agree with previous observational studies showing a dose dependent increased risk of infection associated with (recent) use of oral glucocorticoids.
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- Barbulescu, A., et al.
(författare)
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Effectiveness of baricitinib and tofacitinib compared with bDMARDs in RA: results from a cohort study using nationwide Swedish register data
- 2022
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:10, s. 3952-3962
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To describe the use of baricitinib and tofacitinib by Swedish RA patients and to compare their effectiveness with that of biologic DMARDs (bDMARDs). Methods RA patients who initiated baricitinib (n = 1420), tofacitinib (n = 316), abatacept (n = 1050), IL-6 inhibitors (IL-6is; n = 849), rituximab (n = 1101) or TNF inhibitors (TNFis; n = 6036) between January 2017 and November 2019 were followed for a minimum of 1 year using data from several linked Swedish national registers. Proportions reaching a good EULAR 28-joint DAS (DAS28) response, HAQ Disability Index (HAQ-DI) improvement >0.2 units and Clinical Disease Activity Index (CDAI) remission were compared at 1 year, imputing discontinued treatments as 'non-response'. Additionally, we compared drug retention and changes in DAS28, HAQ-DI and CDAI from baseline to 3 months after treatment initiation. Results On average, baricitinib, and particularly tofacitinib, were initiated as later lines of therapy and more frequently as monotherapy compared with rituximab and TNFi. Adjusted 1 year response proportions were consistently lower on TNFi compared with baricitinib, with differences of -4.3 percentage points (95% CI -8.7, 0.1) for good EULAR response, -9.9 (-14.4 to -5.4) for HAQ-DI improvement and -6.0 (-9.8 to -2.2) for CDAI remission. Comparisons with non-TNFi bDMARDs also favoured baricitinib, but not consistently. Treatment responses for tofacitinib were only marginally lower than those for baricitinib and generally similar to those of bDMARDs, with precision limited by low power. Comparisons of drug retention and changes in disease activity from baseline to 3 months supported the 1 year findings. Conclusions Baricitinib and tofacitinib showed at least equivalent effectiveness compared with bDMARDs after exploring several different effectiveness measures.
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| 8. |
- Barbulescu, A, et al.
(författare)
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Gastrointestinal perforations in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs in Sweden: a nationwide cohort study
- 2020
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Ingår i: RMD open. - : BMJ. - 2056-5933. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- To compare incidence rates of gastrointestinal (GI) perforations between patients with RA and the general population, and between patients treated with tumour necrosis factor inhibitors (TNFi) and non-TNFi biologics.MethodsIn this nationwide cohort study, a total of 63 532 patients with RA, with 26 050 biological treatment episodes (TNFi, rituximab, abatacept or tocilizumab) and 76 304 general population controls, were followed between 2009 and 2017 until the first outcome event. The main outcome was hospitalisation or death due to lower GI perforations, identified according to a prespecified list of ICD-10 (International Classification of Diseases, 10th revision) codes. Inverse probability of treatment weighting was used for adjustment.ResultsThe sex-standardised and age-standardised incidence rates of lower GI perforations were 1.1 (95% CI 1.0 to 1.3) events per 1000 person-years among general population controls, 1.6 (1.5–1.7) among bionaïve patients and ranged from 1.8 (1.4–3.6) (TNFi) to 4.5 (2.7–10.4) (tocilizumab) among biologics-treated patients. After adjustment for glucocorticoid use, the risk in bionaïve, TNFi-treated, abatacept-treated or rituximab-treated patients with RA was no longer different from the general population, while for tocilizumab it remained significantly higher. Comparing tocilizumab to TNFi, the adjusted HR for lower GI perforations was 2.2 (1.3–3.8), corresponding to one additional GI perforation per 451 patient-years treated with tocilizumab instead of TNFi.ConclusionTocilizumab was associated with a higher risk of lower GI perforations compared with alternative biologics. In absolute numbers, the risk remained low on all biologics commonly used to treat RA, but the accumulated evidence across settings and outcome definitions supports that this risk should be considered in treatment guidelines for RA.
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