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- Cordtz, R, et al.
(författare)
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RISK OF HAEMATOLOGICAL MALIGNANCY IN PATIENTS WITH PSORIATIC ARTHRITIS, OVERALL AND IN RELATION TO TNF INHIBITORS - A NORDIC COHORT STUDY
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 169-170
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Several autoimmune inflammatory diseases, including rheumatoid arthritis (RA), are associated with increased risk of malignant lymphomas. There is also a longstanding concern of lymphoma development with tumour necrosis factor inhibitor (TNFi) treatment, but most studies in RA to date do not indicate an additionally increased risk. Corresponding studies in psoriatic arthritis (PsA), both with respect to the underlying risks, and risks in relation to treatment with TNFi, are limited. Data on myeloid malignancies in PsA are scarce.ObjectivesTo estimate the risk of haematological malignancy overall and by lymphoid and myeloid types in TNFi treated versus (vs.) biologics-naïve patients with PsA across the five Nordic countries. Additionally, we investigated the underlying risk of haematological malignancies in PsA as compared to the general population.MethodsWe identified patients with PsA starting a first ever TNFi from the clinical rheumatology registers (CRR) in Sweden (SE), Denmark (DK), Norway (NO), Finland (FI), and Iceland (ICE) from 2006 through 2019 (n=10 621). We identified biologics-naïve patients with PsA from a) the CRR (n=18 705, all countries) and b) the national patient registers (NPR, n=27 286, SE and DK only). To estimate the underlying risk of haematological malignancy in PsA, we randomly sampled general population comparators in SE and DK matched on year of birth, sex, and calendar year at start of follow-up, to the patients with PsA.Through linkage to the mandatory national cancer registers in all five countries, we collected information on haematological malignancy overall, and categorised into lymphoid or myeloid types. By applying a modified Poisson regression, we estimated pooled incidence rate ratio (IRR) with 95% confidence intervals (CI) for TNFi treated vs. biologics-naïve PsA and for PsA vs. the general population, adjusted for age (18-55, 56-65, 66-70, >70 years), sex, calendar period (2006-2010, 2011-2019) and country, and using robust standard errors.ResultsWe observed 40 events of haematological malignancies (during 59 827 person-years) among TNFi treated PsA, resulting in a crude incidence rate (IR) of 67 per 100 000 person-years. The corresponding IR was 91 (63 events) for biologics-naïve PsA from the CRR, and 118 (172 events) for biologics-naïve PsA from NPR. This resulted in a pooled IRR of 0.97 (0.69 to 1.37) for TNFi-treated vs. biologics-naïve PsA patients from the CRR, and 0.84 (0.64 to 1.10) vs. biologics-naïve PsA patients from the NPR. The pooled IRR of haematological malignancies in PsA overall vs. the general population was 1.35 (1.17 to 1.55). Throughout, the estimates were largely similar for lymphoid and myeloid malignancies (Figure 1). The crude IR of haematological malignancies were substantially akin across different TNFi agents.Figure 1.Pooled incidence rate ratios (IRRs) (95% CI) of haematological malignancy overall and by lymphoid and myeloid types, in first ever TNFi treated versus biologics-naïve patients with PsA, and versus general population comparators. Legend: Lymphoid malignancies include international classification of diseases (ICD) 10 codes C81-86, C88, C90-91. Myeloid malignancies include ICD10 codes C92-95, D45-D46, D47.1, D47.3-5. Incidence rate ratios adjusted for age (18-55, 56-65, 66-70, >70 years), sex, calendar period (2006-2010, 2011-2019) and country, and using robust standard errors.ConclusionIn this large five-country cohort study, we did not observe any increased risk of haematological malignancies overall, nor for lymphoid and myeloid types, in patients with PsA treated with TNFi. By contrast, there were signals of a moderately increased underlying risk of haematological malignancies, both of lymphoid and myeloid types, in patients with PsA overall as compared to the general population. The findings are of importance from a patient information perspective.AcknowledgementsWe would like to acknowledge the NordForsk and FOREUM, and especially the patient representatives of the NordForsk collaboration for their valuable contribution to this study.Disclosure of InterestsRené Cordtz: None declared, Johan Askling Consultant of: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Bénédicte Delcoigne: None declared, Karin Ekström Smedby: None declared, Eva Baecklund: None declared, Christine Ballegaard: None declared, Pia Isomäki Speakers bureau: AbbVie, Eli Lilly and Pfizer, Consultant of: AbbVie, Eli Lilly, Pfizer, Roche and ViforPharma, Grant/research support from: Pfizer, Kalle Aaltonen: None declared, Björn Gudbjornsson Speakers bureau: Novartis, not related to this work, Consultant of: Novartis, not related to this work, Thorvardur Love Speakers bureau: Celgene, Sella Aa. Provan: None declared, Brigitte Michelsen Grant/research support from: Novartis, not related to this work, Joe Sexton: None declared, Lene Dreyer Speakers bureau: Eli Lilly, Galderma and Janssen, Grant/research support from: BMS not related to this work, Karin Hellgren: None declared
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- Frisell, T, et al.
(författare)
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SAFETY OF B/TSDMARDS FOR RA AS USED IN CLINICAL PRACTICE - RESULTS FROM THE LAST DECADE OF THE ARTIS PROGRAM
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 587-588
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- While the relative efficacy of treatments can be demonstrated in relatively small studies with limited follow-up, most safety concerns are infrequent, requiring longer follow-up and larger populations. This is recognized by the regulatory framework, where data from pivotal randomized controlled trials are usually considered sufficient for demonstrating efficacy and non-toxicity, but post-approval safety studies are required for many years to fully evaluate drug-associated risks. Though such regulatory safety-studies often focus on one drug (vs. all others), clinical decision-making requires data across all available treatment options. Long-standing longitudinal clinical registries, like the Anti-Rheumatic Therapies in Sweden (ARTIS) database, thus have a key role in assessing the relative safety of b/tsDMARDs, allowing simultaneous comparison of all drugs used in clinical practice, with consistent definitions of treatment cohorts, follow-up, and outcomes.ObjectivesTo assess incidence rates of critical safety endpoints for individual b/tsDMARDs used to treat RA, updating previously published reports and including more recently introduced treatments.MethodsNationwide register-based cohort study including all RA patients in Sweden registered as starting any b/tsDMARD between Jan 1st 2010 and Dec 31st 2019, and followed until Dec 31st 2020. The incidence rates of selected outcomes, identified through national healthcare registers, were compared between individual b/tsDMARDs while adjusting for a range of potential confounders (covering demographics, RA-related characteristics and disease activity, and comorbidity) using Inverse Probability of Treatment Weighting. Probabilities were predicted by multinomial logistic regression, regressing all covariates on treatment status. Exposure time was counted from treatment start until stop (+90 days’ lag time), censored at emigration and death.ResultsThere were clear differences between patients starting individual b/tsDMARDs, in particular with TNF inhibitors more often used as a first line b/tsDMARD; sarilumab, baricitinib, and tofacitinib predominantly used later in the treatment course; rituximab used more often for older patients, and non-TNFi generally used more frequently for patients with higher disease activity or comorbidity. Expectedly, these differences translated into differences in the crude rate of safety endpoints.Several differences remained after confounder-adjustment (Table 1), including a higher rate of treatment discontinuation due to adverse events on baricitinib, tofacitinib, and sarilumab. Rituximab was associated with higher rates of several outcomes, but the confounder-adjustment markedly reduced risks and residual confounding likely explain part of the remaining increase. Baricitinib and tofacitinib were associated with higher rates of hospitalised herpes zoster, but not with similarly elevated rates of other serious infections. There were no clear differences in the rate of cardiovascular events or severe depression. Low number of events limit the comparison, in particular for sarilumab and tofacitinib.Table 1.Weighted incidence rate per 1,000 person-years of selected safety outcomes.DMARDNDiscont. due to. adverse eventACSStrokeLiver diseaseHosp. infectionHosp. Herpes zosterHosp. depressionAny hosp.All-cause mortalityETA8244456.24.51.4322.92.315610.8ADA5069465.95.61.1363.51.51669.5INF2832508.25.83.1433.22.019712.7CER2072546.47.02.5343.61.717211.0GOL1796515.96.8-322.8-15411.5ABA3254567.34.71.9362.31.617213.9RTX3990318.46.22.2413.32.419415.1TCZ2619305.75.02.1312.91.616315.7SAR271100---18--298-BARI1665693.04.21.4378.82.617316.7TOFA39282---3212.9-129-Note: Rates based on <5 events set to ‘-‘.ConclusionWe found large differences in the rate of treatment discontinuations due to adverse events across b/tsDMARDs, which were not generally mirrored by corresponding differences in the rates for specific serious adverse events.ReferencesN/AAcknowledgementsARTIS has been or is currently supported by agreements with Abbvie, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, and Sanofi.Disclosure of InterestsThomas Frisell: None declared, Hannah Bower: None declared, Eva Baecklund: None declared, Daniela Di Giuseppe: None declared, Bénédicte Delcoigne: None declared, Nils Feltelius Employee of: NF is employed by the Medical Products Agency (MPA), which is a governmental body. The views in this abstract may not represent the views of the MPA, Helena Forsblad-d’Elia: None declared, Elisabet Lindqvist: None declared, Ulf Lindström: None declared, Johan Askling Grant/research support from: Karolinska Institutet has entered into agreements with the following companies, with JA as PI: Abbvie,BMS, Eli Lilly, Galapagos, Janssen, Pfizer, Roche, Samsung Bioepis and Sanofi.
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- Sundbaum, Johanna, et al.
(författare)
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Tuberculosis in biologic-naïve patients with rheumatoid arthritis - risk factors and tuberculosis characteristics
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, suppl 1, s. 969-969
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Tidskriftsartikel (refereegranskat)abstract
- Background: The risk of tuberculosis (TB) has decreased in biologic disease modifying anti-rheumatic drugs (bDMARDs) treated rheumatoid arthritis (RA) patients, but remains unaltered 4-fold increased in bio-naïve RA patients compared to the general population in Sweden (1). In absolute numbers, most TB cases in contemporary RA patients occur in the group of bio-naïve patients. Knowledge about risk factors for TB and TB characteristics in bio-naïve RA patients is still limited.Objectives: To investigate risk factors for TB and TB characteristics in bio-naïve RA patients.Methods: Population-based case-control study. A national bio-naïve RA cohort was identified from the National Patient Register and the Swedish Rheumatology Quality Register. RA cases with TB were identified by linkage to the Swedish Tuberculosis Register (with mandatory TB registration) 2001-2014 (n=42). For each case, four matched RA controls without TB were identified. Clinical data were obtained from medical records. Univariate and multivariable logistic regression analyses were used to estimate risk for TB expressed as adjusted (adj) odds ratio (OR) with 95% confidence intervals (CI).Results: After review of the medical records and validation of diagnoses, 31 cases with RA and TB and 122 controls remained in the study. The TB cases had a median of 3 (1-6) reported TB risk factors, and almost 90% were born before 1950. Only one case was screened for TB (with negative result of tuberculin skin test). Active TB occurred at a mean of 15 years after RA diagnosis, and all except three cases were considered as reactivation of latent TB. Exposure to leflunomide (5 cases, 4 controls) (adj OR 6.02; 95% CI 1.47-24.65) and azathioprine (5 cases, 6 controls) (adj OR 3.85; 95% CI 1.06-13.79) were associated with increased risk for TB. Methotrexate, used in 67.7% of cases and 73.9% of controls, was not associated with increased risk of TB (adj OR 0.83; 95% CI 0.34-1.98). Exposure to corticosteroids was more common among cases than controls (74.2% vs 53.8%, p= 0.04), and was associated with an adj OR for TB of 2.44 (95% CI 1.00-5.92). No significant differences were identified between prednisolone-treated cases and controls in terms of maximum dose ever of prednisolone, treatment duration before TB, or cumulative dose of prednisolone during the last year before diagnosis of TB. Obstructive pulmonary disease was the only comorbidity linked to an increased TB risk (adj OR 3.94; 95% CI 1.45-10.69). Pulmonary TB dominated (84%) followed by TB lymphadenitis (19%). Treatment success was 94%, comparable to TB patients in general.Conclusion: Several RA-associated risk factors may contribute to increased TB risk in bio-naïve RA patients (treatment with leflunomide, azathioprine, or prednisolone and concomitant obstructive lung disease). We could not confirm previous findings of an association with the use of moderate to high doses of prednisolone (≥15 mg). TB risk seems difficult to predict with precision in the individual bio-naïve patient based on RA-associated risk factors. To further decrease the TB risk in RA patients TB screening should also be considered in the group of bio-naïve patients.
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