Jarno Rutanen’s research while affiliated with Tampere University and other places

Background The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is used to classify patients with axial spondylarthritis (axSpA) according to disease activity states, particularly when Ankylosing Spondylitis Disease Activity Score (ASDAS) is unavailable. BASDAI values of <2, <4 and >6 are often applied as cut-offs between remission, low (LDA), high (HDA) and very high (VHDA) disease activity, respectively, although this remains unvalidated. Further, sex-based differences in disease activity measures are expected. Objectives We aimed to (i) identify BASDAI cut-offs for disease activity states against predefined external criteria, and (ii) investigate the impact of sex on BASDAI cut-offs. Methods Real-world data from axSpA patients initiating a tumour necrosis factor inhibitor or an interleukin-17A inhibitor from registries participating in the EuroSpA collaboration were analysed. We applied the same approach as previously used to define the endorsed ASDAS cut-offs for disease activity states [1]. Follow-up data at 6 months were used to identify the cut-offs between remission and LDA and between LDA and HDA, while baseline data were identified to select the cut-off for VHDA. Receiver operating characteristic (ROC) were performed analyses to determine the optimal BASDAI values against external criteria (ASAS partial remission and, using thresholds as defined in [1], patient and physician global assessments). Moreover, we conducted separate ROC analyses to identify sex-specific BASDAI cut-offs. The level of agreement between disease activity states based on the estimated and the unvalidated BASDAI cut-offs was also assessed. Results We analysed data from 2,791 patients, of whom 1,708 (61%) were men, from 7 registries with available data on BASDAI and the above-mentioned external criteria (0-10 scale). Mean (SD) BASDAI was 6.1 (1.9) and 3.0 (2.3) at baseline and 6 months, respectively. The optimal BASDAI values against external criteria were estimated to be <1.4, <2.8 and >5.9 (Table 1). The estimated sex-specific BASDAI cut-offs were <1.3, <2.5 and >5.9 for men and <1.6, <2.9 and >5.9 for women, respectively. Figure 1 shows how patients classified in disease activity states according to the cut-offs <2, <4 and >6 were distributed across disease activity states when classified according to the estimated cut-offs. Comparing the estimated and the unvalidated BASDAI cut-offs, 9.1% and 29.8% of patients changed disease activity states at baseline and 6 months, respectively, with corresponding weighted kappa values of 0.91 and 0.72. The level of agreement between disease activity states based on the estimated sex-specific and the unvalidated BASDAI cut-offs was better for women than for men. Conclusion The BASDAI cut-offs for the disease activity states against predefined external criteria were <1.4, <2.8 and >5.9. Our results suggested that sex-based differences in the assessment of disease activity could be considered in clinical practice. REFERENCES [1] Machado et al. (2011). Ann Rheum Dis, 70(1), 47-53. • Download figure • Open in new tab • Download powerpoint • Download figure • Open in new tab • Download powerpoint Figure 1. Stacked bar charts of BASDAI states according to estimated cut-offs dependent on BASDAI states according to unvalidated cut-offs. Disc: proportion of discordance; kappa: weighted kappa coefficient. Acknowledgements Novartis Pharma AG and IQVIA for supporting the EuroSpA collaboration. Disclosure of Interests Stylianos Georgiadis Novartis, Lykke Midtbøll Ørnbjerg Novartis, Brigitte Michelsen Novartis, Novartis, Tore K. Kvien Grünenthal, Sandoz, UCB, AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB, AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, UCB, Simon Horskjær Rasmussen Novartis, Karel Pavelka AbbVie, UCB, Pfizer, Eli Lilly, Celltrion, MSD, Novartis, Jakub Zavada Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, Astra Zeneca, Sobi, Bente Glintborg Abbvie, BMS, Pfizer, Sandoz, Anne Gitte Loft Pfizer, AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Novartis, Ana Maria Rodrigues Abbvie, Amgen, Abbvie, Amgen, Amgen, Novartis, Pfizer, Maria José Santos Abbvie, AstraZeneca, Janssen, Lilly, Medac, Novartis, Pfizer, Adrian Ciurea: None declared, Michael J. Nissen AbbVie, Amgen, Eli Lilly, Janssens, Novartis, Pfizer, AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Novartis, Pfizer, Laura Kuusalo Abbvie, Lilly, Medac, Orion, Pfizer, UCB, Gilead, Pfizer, Jarno Rutanen: None declared, Ziga Rotar Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Lek, MSD, Medis, Novartis, Pfizer, Sanofi, Abbvie, AstraZeneca, Eli Lilly, Janssen, Novartis, Pfizer, SOBI, Swixx BioPharma, Katja Perdan Pirkmajer Abbvie, Eli Lilly, Janssen, Lek, Medis, MSD, Novartis, Pfizer, Abbvie, Boehringer Ingelheim, Eli Lilly, Medis, Novartis, Pfizer, Bjorn Gudbjornsson Novartis, Nordic-Pharma, Novartis, Olafur Palsson: None declared, Daniela Di Giuseppe: None declared, Mikkel Østergaard Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Abbvie, BMS, Merck, Novartis, UCB, Merete Lund Hetland Pfizer, Medac, Sandoz, Abbvie, Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk.

We report the short- and long-term results of the SOLIDARITY Finland on mortality and other patient-important outcomes in patients hospitalised for COVID-19. Between 08/2021 and 03/2023, we randomised 156 patients in 15 hospitals. In the imatinib group, 7.2% of patients had died at 30 days and 13.3% at 1 year and in the standard of care group 4.1% and 8.3% (adjusted HR at 30 days 1.09, 95% CI 0.23-5.07). In a meta-analysis of randomised trials of imatinib versus standard of care (n=732), allocation to imatinib was associated with a mortality risk ratio of 0.73 (95% CI 0.32-1.63). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.3% in standard of care (RR 0.91, 95% CI 0.78-1.06). Of the 21 potential long COVID symptoms, patients often reported moderate or major bother from fatigue (24%), sleeping problems (19%) and memory difficulties (17%). We found no convincing difference between imatinib and standard of care groups in quality of life or symptom outcomes. The evidence raises serious doubts regarding the benefit of imatinib in reducing mortality, improving recovery and preventing potential long COVID symptoms when given to patients hospitalised for COVID-19.

Objective The aim was to investigate the effect of TNF inhibitor (TNFi) initiation on working ability and health-care resource utilization among axial SpA patients in a real-life setting. Methods Patients with a clinical diagnosis of non-radiographic (nr-axSpA) or radiographic axial SpA initiating their first TNFi were identified from the National Register for Antirheumatic and Biologic Treatment in Finland. Sickness absences, including sick leave and disability pension, in- and outpatient days and rehabilitation rates, 1 year before and after initiating the medication were retrieved from national registries. Factors affecting result variables were studied using multivariate regression analysis. Results Overall, 787 patients were identified. Rates of work disability days per year were 55.6 the year before treatment onset and 55.2 the year after, with significant differences between patient subgroups. The rate of sick leave decreased after starting TNFi treatment. However, the rate of disability pension continued to rise. Patients with a diagnosis of nr-axSpA experienced a decrease in overall work disability and, especially, fewer sick leaves. No sex differences were detected. Conclusion TNFi interrupts the increase in work disabled days evident during the year before its initiation. However, the overall work disability remains high. Treating patients earlier in the nr-axSpA phase, regardless of sex, appears important in maintaining the ability to work.

Background Coronavirus disease 2019 (COVID-19) patients frequently suffer from long-term sequelae, often called “long COVID” or “post COVID-19 condition”. Remdesivir, given in early disease, decreases the risk of hospitalization and potentially mortality. No randomized trials have thus far published long-term follow-up data on any COVID-19 drug treatment. We investigated the effects of remdesivir on a range of patient-important outcomes at one year. Methods Between July 2020 and January 2021, an open-label randomized multicenter trial in Finland recruited 208 adult patients from 11 Finnish hospitals. Patients were randomly assigned (1:1 ratio) to standard of care (SoC)with remdesivir (median duration of remdesivir treatment 5 days) or SoC alone. Primary outcomes were self-reported recovery, exertional dyspnea, fatigue, and quality of life at one year. Secondary outcomes were overall mortality and several potential long-COVID symptoms. Results At one year, 5 (4.4%) of 114 patients in the remdesivir and 5 (5.3%) of 94 in the SoC group had died (RR 0.82, 95% CI 0.25-2.76; absolute difference: -0.9%, 95% CI -7.9-5.3); 181 (92% of survivors) completed the follow-up. Self-reported recovery (fully or largely) occurred in 85% in remdesivir and in 86% in SoC (RR 0.94, 0.47-1.90; absolute difference: -0.9%, 95% CI -11%-10%). Exertional dyspnea occurred in 5% in remdesivir and 8% in SoC (OR 0.61, 95% CI 0.20-1.85; absolute difference -3.3%, 95% CI -12%-4.4%). We found no convincing difference between remdesivir and SoC groups in quality of life or symptom outcomes (p > 0.05 for all). Of the 21 potential long-COVID symptoms, patients often reported moderate or major bother from fatigue (26%), joint pain (22%), persistent respiratory mucus (21%), and problems with memory (19%) and attention/concentration (18%) (Figure). Bother from potential long-COVID symptoms at one year from COVID-19 hospitalization between the standard of care and standard of care plus remdesivir groups. Conclusion After a one-year follow-up of hospitalized patients (with a very high participation rate), approximately one in four reported substantial bother from fatigue, and one in six reported that they had not recovered well from COVID-19. We found no convincing evidence of a remdesivir effect, but confidence intervals were wide and included possible substantial benefit and substantial harm. Disclosures Hanna-Riikka Kreivi, MD, PhD, Pfizer: Advisor/Consultant|Roche: Advisor/Consultant Tuomas Rosberg, MD, PhD, AstraZeneca: Honoraria|Boehringer-Ingelheim: Honoraria|GSK: Honoraria.

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes ( p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.

Background Little comparative research has been done comparing disease burden between PsA and RA. Previous studies from Nordic countries and the US have shown small differences (0-10/100 VAS units) in patients with PsA vs. RA. The mean and median VAS levels for PsA and RA ranged between 30-40 for pain and 40-50 for fatigue and patient global health in cross-sectional settings (1, 2, 3). Objectives To study the current differences in PROs between PsA and RA in Finland. Methods 3731 patients receiving care for PsA and 14163 for RA were identified in the national quality register for inflammatory arthritides in 2020-21. Patients were divided into groups by sex and age; <50 years, 50-60 years, 60-70 years and ≥70 years. The VAS values of pain, fatigue and patient global health at the most recent visit were compared in PsA vs. RA between the groups. Descriptive statistics and regression models were used for comparison. Results Patients with PsA vs RA were younger (mean (sd) age 54(14) vs 62(14)) and less often women (51% vs. 72%). Median (IQR) disease duration after the first symptoms was 8.6 (3.7, 17) years for PsA and 9.5 (3.3, 21) years for RA. The median (IQR) pain was 29 (10, 56) for all patients with PsA and 26 (10,51) for patients with RA. The corresponding values were: fatigue 28 (9, 60) in PsA vs 28 (8, 54) in RA, and patient global health 28 (10, 51) in PsA and 29 (11, 51) in RA. Median pain was slightly higher in female PsA patients compared to RA patients in all age groups (29 and 18, 35 and 28, 32 and 27 and 48 and 38) (p<0.001). In males, higher levels of pain in PsA vs. RA were seen in age groups older than 50 years old. Figure 1 illustrates the mean (95% CI) pain for PsA and RA in the age and sex groups. Median fatigue levels were quite similar between the groups. The median patient global health was higher in female PsA compared to RA patients in age groups <50 years and 50-60 years (20 vs. 29 and 30 vs 37) (p<0.001). Figure 1. Mean (95 % CI) pain in VAS-units for women and men by age groups in 2020-2021 Conclusion Female patients with PsA report higher levels of pain in all age groups compared to patients with RA. The same was seen in men >50 years old. Concerning fatigue and patient global health, the differences between PsA and RA were smaller. Compared to earlier research in other countries, disease burden observed by PROs appears lower both in PsA and RA in Finland. References [1]Pilgaard T et al. Severity of fatigue in people with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis – Results of a cross-sectional study, PLoS One, 2019; 14(6): e0218831 [2]Egholm CL et al. Discordance of Global Assessments by Patient and Physician Is Higher in Female than in Male Patients Regardless of the Physician’s Sex: Data on Patients with Rheumatoid Arthritis, Axial Spondyloarthritis, and Psoriatic Arthritis from the DANBIO Registry, The Journal of rheumatology, 2015 Oct;42(10):1781-5. [3]Mease PJ et al. Comparative Disease Burden in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, or Axial Spondyloarthritis: Data from Two Corrona Registries, Rheumatology and therapy, 2019 Dec;6(4):529-542 Acknowledgements I would like to thank The Finnish Society for Rheumatology and The Finnish Psoriasis Association for their grants. Disclosure of Interests None declared

Background Worries have been expressed, concerning the care of chronic diseases during the Covid times (1). Objectives To study the current status of patients with RA in the Finnish quality register database. Methods Patients who receive care for RA were identified in the database. Clinical and demographic data from the last visits during 2020-21 were collected, including swollen (SJC46) and tender joint counts (TJC46), doctor assessment of disease activity (Dr global), laboratory tests for inflammatory and serology markers, patient reported outcomes (PROs), and DAS28. Regression models were applied to compare measures of clinical status between the health care regions, adjusted for gender, age, ACPA status, and disease duration. Results A total of 14163 patients (72% female, mean (SD) age 62 (14) years, median (IQR) disease duration 8.5 (2.6, 20) years, 84% ACPA positive) were identified. For the entire population, the median (IQR) SJC46 was 0 (0, 1), TJC46 0 (0, 2), ESR 8 (5, 18), CRP 3 (1, 6), and dr global 8 (0, 19). Among PROs, median (IQR) HAQ was 0.5 (0, 1), pain 26 (10, 51), fatigue 28 (8, 54) and patient global 29 (11, 51). Between health care regions, statistically significant differences were found for all variables due to a large sample size. The mean (SD) DAS28 was 2.3 (0.9) for the entire group and 69 % of all patients had DAS28<2.6. The median DAS28 ranged from 2 to 2.7 among health care regions (Figure 1) (p<0.001). Majority of patients were taking csDMARDs only. Figure 1. Rheumatoid arthritis in 2020-21: The median DAS28-values in 19 regions in Finland. Conclusion The quality register provides comprehensive real-world data on the current status of patients with RA. A majority of patients can be considered being in remission even during the Covid times. References [1] Glintborg et al. Rheumatology (Oxford) 2021 Oct 9;60(SI):SI3-SI12 Acknowledgements I would like to thank The Finnish Society for Rheumatology and The Finnish Psoriasis Association for their grants. Disclosure of Interests None declared