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5. Drug effectiveness of 2nd and 3rd TNF inhibitors in psoriatic arthritis – relationship with the reason for withdrawal from the previous treatment

Author

Ørnbjerg, Lykke Midtbøll, Brahe, Cecilie Heegaard, Linde, Louise, Jacobsson, Lennart, Nissen, Michael J., Kristianslund, Eirik Klami, Santos, Maria José, Nordström, Dan, Rotar, Ziga, Gudbjornsson, Bjorn, Onen, Fatos, Codreanu, Catalin, Lindström, Ulf, Möller, Burkhard, Kvien, Tore K., Barcelos, Anabela, Eklund, Kari K., Tomšič, Matija, Love, Thorvardur Jon, Can, Gercek, Ionescu, Ruxandra, Loft, Anne Gitte, Mann, Herman, Pavelka, Karel, van de Sande, Marleen, van der Horst-Bruinsma, I.E., Suarez, Manuel Pombo, Sánchez-Piedra, Carlos, Macfarlane, Gary J., Iannone, Florenzo, Michelsen, Brigitte, Hyldstrup, Lise Hejl, Krogh, Niels Steen, Østergaard, Mikkel, and Hetland, Merete Lund

Published
2024
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6. Truncating NFKB1 variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis

Author

Nurmi, Katariina, Silventoinen, Kristiina, Keskitalo, Salla, Rajamäki, Kristiina, Kouri, Vesa-Petteri, Kinnunen, Matias, Jalil, Sami, Maldonado, Rocio, Wartiovaara, Kirmo, Nievas, Elma Inés, Denita-Juárez, Silvina Paola, Duncan, Christopher J.A., Kuismin, Outi, Saarela, Janna, Romo, Inka, Martelius, Timi, Parantainen, Jukka, Beklen, Arzu, Bilicka, Marcelina, Matikainen, Sampsa, Nordström, Dan C., Kaustio, Meri, Wartiovaara-Kautto, Ulla, Kilpivaara, Outi, Klein, Christoph, Hauck, Fabian, Jahkola, Tiina, Hautala, Timo, Varjosalo, Markku, Barreto, Goncalo, Seppänen, Mikko R.J., and Eklund, Kari K.

Published
2024
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12. Epstein-Barr Virus in the Cerebrospinal Fluid and Blood Compartments of Patients With Multiple Sclerosis and Controls

Author

Lehikoinen, Joonas, primary, Nurmi, Katariina, additional, Ainola, Mari, additional, Clancy, Jonna, additional, Nieminen, Janne K., additional, Jansson, Lilja, additional, Vauhkonen, Hanna, additional, Vaheri, Antti, additional, Smura, Teemu, additional, Laakso, Sini M., additional, Eklund, Kari K., additional, and Tienari, Pentti J., additional

Published
2024
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13. Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction: The randomized, double-blind, placebo-controlled OXI pilot trial

Author

Ulander, Lotta, Tolppanen, Heli, Hartman, Otto, Rissanen, Tuomas T., Paakkanen, Riitta, Kuusisto, Jouni, Anttonen, Olli, Nieminen, Tuomo, Yrjölä, Jaana, Ryysy, Ransu, Drews, Teemu, Utriainen, Seppo, Karjalainen, Pasi, Anttila, Ismo, Nurmi, Katariina, Silventoinen, Kristiina, Koskinen, Miika, Kovanen, Petri T., Lehtonen, Jukka, Eklund, Kari K., and Sinisalo, Juha

Published
2021
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14. Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study.

Author

Kerola, Anne M, Palomäki, Antti, Laivuori, Hannele, Laitinen, Tarja, Färkkilä, Martti, Eklund, Kari K, Ripatti, Samuli, Perola, Markus, Ganna, Andrea, Lindbohm, Joni V, and Mars, Nina

Subjects
CELIAC disease complications, RISK factors of preeclampsia, CESAREAN section, TYPE 1 diabetes, REPRODUCTIVE health, SECONDARY analysis, JUVENILE idiopathic arthritis, SMALL for gestational age, PSORIASIS, RESEARCH funding, SEX distribution, PREMATURE infants, NEONATAL intensive care units, SYSTEMIC lupus erythematosus, NEONATAL intensive care, PREGNANCY outcomes, LONGITUDINAL method, INFLAMMATORY bowel diseases, INFLAMMATION, SJOGREN'S syndrome, RHEUMATISM, IMMUNOLOGIC diseases, EDUCATIONAL attainment, CHILDLESSNESS, ADDISON'S disease, ASTHMA, THROMBOPENIC purpura, DISEASE complications
Abstract

Objectives Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs). Methods Out of all of the 5 339 804 Finnish citizens, individuals born 1964–1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes. Results Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1–1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis. Conclusion Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Sex Differences in the Effectiveness of First‐Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network

Author

Hellamand, Pasoon, primary, van de Sande, Marleen G. H., additional, Ørnbjerg, Lykke M., additional, Klausch, Thomas, additional, Eklund, Kari K., additional, Relas, Heikki, additional, Santos, Maria J., additional, Vieira‐Sousa, Elsa, additional, Loft, Anne G., additional, Glintborg, Bente, additional, Østergaard, Mikkel, additional, Lindström, Ulf, additional, Wallman, Johan K., additional, Michelsen, Brigitte, additional, Fagerli, Karen M., additional, Castrejón, Isabel, additional, Gudbjornsson, Bjorn, additional, Love, Thorvardur J., additional, Vencovský, Jiří, additional, Nekvindová, Lucie, additional, Rotar, Žiga, additional, Tomšič, Matija, additional, Díaz‐González, Federico, additional, Kenar, Gökçe, additional, Tuğsal, Handan Y., additional, Iannone, Florenzo, additional, Ramonda, Roberta, additional, Codreanu, Catalin, additional, Mogosan, Corina, additional, Nissen, Michael J., additional, Möller, Burkhard, additional, Hetland, Merete L., additional, and van der Horst‐Bruinsma, Irene E., additional

Published
2024
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18. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial

Author

Morin, Frederic, Rahman, Proton, Ariel, Federico, Berman, Alberto, Carrio, Judith, Lucero, Eleonora, Cocco, Jose Maldonado, Hidalgo, Rodolfo Pardo, Velasco, Jorge, Viola, Diego O., Grisar, Johannes, Resch, Heinrich, Scheinecker, Clemens, Melazzi, Ana Claudia, Roimicher, Luis, Scotton, Antonio Scafuto, Rodriguez, Aaron Alejandro Barrera, Molina, Francisco Fidencio Cons, Barragan, Sergio Duran, Skinner, Cassandra M., Tena, Cesar Francisco Pacheco, Remus, Cesar Ricardo Ramos, Rodriguez, Juan Cruz Rizo, Hong, Seung-Jae, Kang, Seong Wook, Lee, Chang Keun, Lee, Eun Bong, Lee, Sang Heon, Park, Min-Chan, Lee, Sang-Hoon, Dokoupilova, Eva, Dvorak, Zdenek, Malcova, Martina, Pvelka, Karel, Eklund, Kari K., Jarvinen, Pentti, Karjalainen, Anna, Paimela, Leena, Taniguchi, Yoshinori, Tsuda, Tokutaro, Tada, Kurisu, Dobashi, Hiroaki, Inui, Kentaro, Ueki, Yukitaka, Matsumoto, Yoshifuji, Hatta, Kazuhiro, Atsumi, Tatsuya, Goto, Hitoshi, Honjo, Shigeru, Matsui, Kiyoshi, Takakubo, Yuya, Neeck, Gunther, Wagner, Sylke, Braun, Jürgen, Blicharshi, Tomasz, Dudek, Anna, Hrycai, Pawel, Plebanski, Rafal, Drabiszcak-Piatkowska, Janina, Brzezicki, Jan, Krogulec, Marek, Opris-Belinski, Daniela, Ramazan, Ana Maria, Tronaru, Luminita, van de Sande, Marleen G., Matsievskaya, Galina, Schmidt, Evgeniya, Stanislav, Marina, Yakushin, Sergey, Ershova, Olga, Rebroy, Andrey, Churchill, Melvin A., Flint, Kathleen P., Greenwald, Maria, Howell, Mary P., Kaine, Jeffrey L., Kivitz, Alan, Klein, Steven J., Mueller, Eric C., Peters, Eric A., Querubin, Roel, Sayers, Michael E., Scoville, Craig D., Shanahan, Joseph C., Roseff, Richard, Hull, John E., Mallepalli, Jyothi R., Sebai, Mohamed B., Kimmel, Steven C., Goddard, David H., Mease, Philip J., Harris, Mark D., Mabaquiao, Arthur R., Diegel, Roger J., Thai, Christine, Rivera, Tania L., Perez-De Jesus, Amarilis, Soto-Raices, Oscar, Toro-Torres, Ramon, Pantojas, Carlos, Deodhar, Atul, van der Heijde, Désirée, Gensler, Lianne S, Kim, Tae-Hwan, Maksymowych, Walter P, Østergaard, Mikkel, Poddubnyy, Denis, Marzo-Ortega, Helena, Bessette, Louis, Tomita, Tetsuya, Leung, Ann, Hojnik, Maja, Gallo, Gaia, Li, Xiaoqi, Adams, David, Carlier, Hilde, and Sieper, Joachim

Published
2020
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19. Real‐World Six‐ and Twelve‐Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries

Author

Michelsen, Brigitte, Georgiadis, Stylianos, Di Giuseppe, Daniela, Loft, Anne G., Nissen, Michael J., Iannone, Florenzo, Pombo‐Suarez, Manuel, Mann, Herman, Rotar, Ziga, Eklund, Kari K., Kvien, Tore K., Santos, Maria J., Gudbjornsson, Bjorn, Codreanu, Catalin, Yilmaz, Sema, Wallman, Johan K., Brahe, Cecilie H., Möller, Burkhard, Favalli, Ennio G., Sánchez‐Piedra, Carlos, Nekvindova, Lucie, Tomsic, Matija, Trokovic, Nina, Kristianslund, Eirik K., Santos, Helena, Löve, Thorvardur J., Ionescu, Ruxandra, Pehlivan, Yavuz, Jones, Gareth T., van der Horst‐Bruinsma, Irene, Ørnbjerg, Lykke M., Østergaard, Mikkel, and Hetland, Merete L.

Published
2022
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20. Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis:Results From the European Spondyloarthritis Research Collaboration Network

Author

Hellamand, Pasoon, van de Sande, Marleen G.H., Ørnbjerg, Lykke M., Klausch, Thomas, Eklund, Kari K., Relas, Heikki, Santos, Maria J., Vieira-Sousa, Elsa, Loft, Anne G., Glintborg, Bente, Østergaard, Mikkel, Lindström, Ulf, Wallman, Johan K., Michelsen, Brigitte, Fagerli, Karen M., Castrejón, Isabel, Gudbjornsson, Bjorn, Love, Thorvardur J., Vencovský, Jiří, Nekvindová, Lucie, Rotar, Žiga, Tomšič, Matija, Díaz-González, Federico, Kenar, Gökçe, Tuğsal, Handan Y., Iannone, Florenzo, Ramonda, Roberta, Codreanu, Catalin, Mogosan, Corina, Nissen, Michael J., Möller, Burkhard, Hetland, Merete L., van der Horst-Bruinsma, Irene E., Hellamand, Pasoon, van de Sande, Marleen G.H., Ørnbjerg, Lykke M., Klausch, Thomas, Eklund, Kari K., Relas, Heikki, Santos, Maria J., Vieira-Sousa, Elsa, Loft, Anne G., Glintborg, Bente, Østergaard, Mikkel, Lindström, Ulf, Wallman, Johan K., Michelsen, Brigitte, Fagerli, Karen M., Castrejón, Isabel, Gudbjornsson, Bjorn, Love, Thorvardur J., Vencovský, Jiří, Nekvindová, Lucie, Rotar, Žiga, Tomšič, Matija, Díaz-González, Federico, Kenar, Gökçe, Tuğsal, Handan Y., Iannone, Florenzo, Ramonda, Roberta, Codreanu, Catalin, Mogosan, Corina, Nissen, Michael J., Möller, Burkhard, Hetland, Merete L., and van der Horst-Bruinsma, Irene E.

Abstract

Objective Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. Methods Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan–Meier estimator. Results We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80–0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81–0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). Conclusion Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management., Objective: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. Methods: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan–Meier estimator. Results: We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80–0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81–0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). Conclusion: Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.

Published
2024

21. Gain-of-function CEBPE mutation causes noncanonical autoinflammatory inflammasomopathy

Author

Göös, Helka, Fogarty, Christopher L., Sahu, Biswajyoti, Plagnol, Vincent, Rajamäki, Kristiina, Nurmi, Katariina, Liu, Xiaonan, Einarsdottir, Elisabet, Jouppila, Annukka, Pettersson, Tom, Vihinen, Helena, Krjutskov, Kaarel, Saavalainen, Päivi, Järvinen, Asko, Muurinen, Mari, Greco, Dario, Scala, Giovanni, Curtis, James, Nordström, Dan, Flaumenhaft, Robert, Vaarala, Outi, Kovanen, Panu E., Keskitalo, Salla, Ranki, Annamari, Kere, Juha, Lehto, Markku, Notarangelo, Luigi D., Nejentsev, Sergey, Eklund, Kari K., Varjosalo, Markku, Taipale, Jussi, and Seppänen, Mikko R.J.

Published
2019
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22. Second and third TNF inhibitors in European patients with axial spondyloarthritis: effectiveness and impact of the reason for switching.

Author

Linde, Louise, Ørnbjerg, Lykke Midtbøll, Brahe, Cecilie Heegaard, Wallman, Johan Karlsson, Giuseppe, Daniela Di, Závada, Jakub, Castrejon, Isabel, Díaz-Gonzalez, Federico, Rotar, Ziga, Tomšič, Matija, Glintborg, Bente, Gudbjornsson, Bjorn, Geirsson, Arni Jon, Michelsen, Brigitte, Kristianslund, Eirik Klami, Santos, Maria José, Barcelos, Anabela, Nordström, Dan, Eklund, Kari K, and Ciurea, Adrian

Subjects
ANTI-inflammatory agents, THERAPEUTICS, RESEARCH funding, ANKYLOSIS, TERMINATION of treatment, EUROPEANS, ANTIRHEUMATIC agents, TREATMENT effectiveness, REPORTING of diseases, DESCRIPTIVE statistics, LONGITUDINAL method, REMISSION induction, SPONDYLOARTHROPATHIES, GENERIC drug substitution
Abstract

Objective To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with (i) treatment line (second and third TNFi-series) and (ii) reason for withdrawal from the preceding TNFi [lack of efficacy (LOE) vs adverse events (AE)]. Methods Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission [Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)] were assessed in second and third TNFi-series and stratified by withdrawal reason. Results We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE vs LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE <26 vs ≥26 weeks) (58% vs 71%, P  < 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) vs LOE (17%), P  < 0.001, while similar for the third TNFi (19% vs 13%, P  = 0.20). Conclusion A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE vs LOE. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Second and third TNF inhibitors in European patients with axial spondyloarthritis: effectiveness and impact of the reason for switching

Author

Linde, Louise, primary, Ørnbjerg, Lykke Midtbøll, additional, Heegaard Brahe, Cecilie, additional, Wallman, Johan Karlsson, additional, Di Giuseppe, Daniela, additional, Závada, Jakub, additional, Castrejon, Isabel, additional, Díaz-Gonzalez, Federico, additional, Rotar, Ziga, additional, Tomšič, Matija, additional, Glintborg, Bente, additional, Gudbjornsson, Bjorn, additional, Geirsson, Arni Jon, additional, Michelsen, Brigitte, additional, Kristianslund, Eirik Klami, additional, Santos, Maria José, additional, Barcelos, Anabela, additional, Nordström, Dan, additional, Eklund, Kari K, additional, Ciurea, Adrian, additional, Nissen, Michael, additional, Akar, Servet, additional, Hejl Hyldstrup, Lise, additional, Krogh, Niels Steen, additional, Hetland, Merete Lund, additional, and Østergaard, Mikkel, additional

Published
2023
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28. A Family With A20 Haploinsufficiency Presenting With Novel Clinical Manifestations and Challenges for Treatment

Author

Hautala, Timo, Vähäsalo, Paula, Kuismin, Outi, Keskitalo, Salla, Rajamäki, Kristiina, Väänänen, Antti, Simojoki, Marja, Säily, Marjaana, Pelkonen, Ilpo, Tokola, Heikki, Mäkinen, Markus, Kaarteenaho, Riitta, Jartti, Airi, Hautala, Nina, Kantola, Saara, Jackson, Päivi, Glumoff, Virpi, Saarela, Janna, Varjosalo, Markku, Eklund, Kari K., and Seppänen, Mikko R. J.

Published
2020
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31. Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans

Author

Kaasinen, Eevi, Kuismin, Outi, Rajamäki, Kristiina, Ristolainen, Heikki, Aavikko, Mervi, Kondelin, Johanna, Saarinen, Silva, Berta, Davide G., Katainen, Riku, Hirvonen, Elina A. M., Karhu, Auli, Taira, Aurora, Tanskanen, Tomas, Alkodsi, Amjad, Taipale, Minna, Morgunova, Ekaterina, Franssila, Kaarle, Lehtonen, Rainer, Mäkinen, Markus, Aittomäki, Kristiina, Palotie, Aarno, Kurki, Mitja I., Pietiläinen, Olli, Hilpert, Morgane, Saarentaus, Elmo, Niinimäki, Jaakko, Junttila, Juhani, Kaikkonen, Kari, Vahteristo, Pia, Skoda, Radek C., Seppänen, Mikko R. J., Eklund, Kari K., Taipale, Jussi, Kilpivaara, Outi, and Aaltonen, Lauri A.

Published
2019
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32. Second and third TNF inhibitors in European patients with axial spondyloarthritis: Effectiveness and impact of the reason for switching

Author

Linde, Louise; https://orcid.org/0000-0003-0863-1352, Ørnbjerg, Lykke Midtbøll; https://orcid.org/0000-0002-7832-6831, Brahe, Cecilie Heegaard; https://orcid.org/0000-0002-1790-5610, Wallman, Johan Karlsson, Di Giuseppe, Daniela, Závada, Jakub, Castrejon, Isabel, Díaz-Gonzalez, Federico, Rotar, Žiga, Tomšič, Matija; https://orcid.org/0000-0002-4507-9010, Glintborg, Bente; https://orcid.org/0000-0002-8931-8482, Gudbjornsson, Bjorn, Geirsson, Árni Jón, Michelsen, Brigitte; https://orcid.org/0000-0003-0103-2840, Kristianslund, Eirik Klami, Santos, Maria José; https://orcid.org/0000-0002-7946-1365, Barcelos, Anabela, Nordström, Dan, Eklund, Kari K, Ciurea, Adrian; https://orcid.org/0000-0002-7870-7132, Nissen, Michael J; https://orcid.org/0000-0002-6326-1764, Akar, Servet, Hyldstrup, Lise Hejl, Krogh, Niels Steen, Hetland, Merete Lund, Østergaard, Mikkel, Linde, Louise; https://orcid.org/0000-0003-0863-1352, Ørnbjerg, Lykke Midtbøll; https://orcid.org/0000-0002-7832-6831, Brahe, Cecilie Heegaard; https://orcid.org/0000-0002-1790-5610, Wallman, Johan Karlsson, Di Giuseppe, Daniela, Závada, Jakub, Castrejon, Isabel, Díaz-Gonzalez, Federico, Rotar, Žiga, Tomšič, Matija; https://orcid.org/0000-0002-4507-9010, Glintborg, Bente; https://orcid.org/0000-0002-8931-8482, Gudbjornsson, Bjorn, Geirsson, Árni Jón, Michelsen, Brigitte; https://orcid.org/0000-0003-0103-2840, Kristianslund, Eirik Klami, Santos, Maria José; https://orcid.org/0000-0002-7946-1365, Barcelos, Anabela, Nordström, Dan, Eklund, Kari K, Ciurea, Adrian; https://orcid.org/0000-0002-7870-7132, Nissen, Michael J; https://orcid.org/0000-0002-6326-1764, Akar, Servet, Hyldstrup, Lise Hejl, Krogh, Niels Steen, Hetland, Merete Lund, and Østergaard, Mikkel

Abstract

OBJECTIVE: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with 1) treatment line (second and third TNFi-series) and 2) reason for withdrawal from the preceding TNFi (lack of efficacy (LOE) versus adverse events (AE)). METHODS: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission (Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)) were assessed in second and third TNFi-series and stratified by withdrawal reason. RESULTS: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE versus LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE < 26 versus ≥26 weeks) (58% versus 71%, p< 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) versus LOE (17%), p< 0.001, while similar for the third TNFi (19% versus 13%, p= 0.20). CONCLUSION: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE versus LOE.

Published
2023

36. Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae

Author

Tuovinen, Elina A., primary, Kuismin, Outi, additional, Soikkonen, Leila, additional, Martelius, Timi, additional, Kaustio, Meri, additional, Hämäläinen, Sari, additional, Viskari, Hanna, additional, Syrjänen, Jaana, additional, Wartiovaara-Kautto, Ulla, additional, Eklund, Kari K., additional, Saarela, Janna, additional, Varjosalo, Markku, additional, Kere, Juha, additional, Hautala, Timo, additional, and Seppänen, Mikko R.J., additional

Published
2023
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37. Heterozygous premature termination in zinc-finger domain of Krüppel-like factor 2 gene associates with dysregulated immunity

Author

Pernaa, Nora, primary, Keskitalo, Salla, additional, Chowdhury, Iftekhar, additional, Nissinen, Antti, additional, Glumoff, Virpi, additional, Keski-Filppula, Riikka, additional, Junttila, Juhani, additional, Eklund, Kari K., additional, Santaniemi, Wenny, additional, Siitonen, Sanna, additional, Seppänen, Mikko RJ., additional, Vähäsalo, Paula, additional, Varjosalo, Markku, additional, Åström, Pirjo, additional, and Hautala, Timo, additional

Published
2022
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39. Short interruptions of TNF-inhibitor treatment can be associated with treatment failure in patients with immune-mediated diseases

Author

BLING Res Grp, Lamberg, Tea, Sipponen, Taina, Valtanen, Sanna, Eklund, Kari K., Mälkönen, Tarja, Aalto, Kristiina, Mikola, Katriina, Kolho, Kaija-Leena, Leinonen, Sanna, Isomäki, Pia, Mäkinen, Heidi, Vidqvist, Krista-Liisa, Kokko, Arto, Huilaja, Laura, Kyllönen, Minna, Keskitalo, Paula, Sard, Sirja, Vähäsalo, Paula, Koskela, Ritva, Kröger, Liisa, Lahtinen, Perttu, Haapala, Anna-Maija, Korkatti, Katja, Sokka-Isler, Tuulikki, Jokiranta, T. Sakari, HUSLAB, University of Helsinki, Clinicum, Gastroenterologian yksikkö, HUS Abdominal Center, HUS Inflammation Center, Department of Medicine, Reumatologian yksikkö, Department of Dermatology, Allergology and Venereology, HUS Children and Adolescents, Children's Hospital, HYKS erva, Päijät-Häme Welfare Consortium, Medicum, Tampere University, Clinical Medicine, Eye Centre, Department of Internal medicine, and Department of Clinical Microbiology

Subjects
rheumatoid arthritis, Immunology, DISCONTINUATION, 3121 Internal medicine, THERAPY, BIOLOGICS, Rheumatic Diseases, adalimumab, Humans, Immunology and Allergy, DRUGS, Treatment Failure, Finland, Retrospective Studies, ulcerative colitis, REGISTER, Drug Substitution, treatment interruption, immunisation, Crohn disease, Infliximab, RHEUMATOID-ARTHRITIS, Case-Control Studies, 3121 General medicine, internal medicine and other clinical medicine, ANTIBODIES, juvenile idiopathic arthritis, Tumor Necrosis Factor Inhibitors, INFLAMMATORY-BOWEL-DISEASE
Abstract

Introduction: The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment. Material and methods: This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases. Results: Treatment interruptions were associated with immunisation in patients using infliximab (p

Published
2022

45. Short interruptions of TNF-inhibitor treatment can be associated with treatment failure in patients with immune-mediated diseases

Author

Lamberg, Tea, primary, Sipponen, Taina, additional, Valtanen, Sanna, additional, Eklund, Kari K, additional, Mälkönen, Tarja, additional, Aalto, Kristiina, additional, Mikola, Katriina, additional, Kolho, Kaija-Leena, additional, Leinonen, Sanna, additional, Isomäki, Pia, additional, Mäkinen, Heidi, additional, Vidqvist, Krista-Liisa, additional, Kokko, Arto, additional, Huilaja, Laura, additional, Kyllönen, Minna, additional, Keskitalo, Paula, additional, Sard, Sirja, additional, Vähäsalo, Paula, additional, Koskela, Ritva, additional, Kröger, Liisa, additional, Lahtinen, Perttu, additional, Haapala, Anna-Maija, additional, Korkatti, Katja, additional, Sokka-Isler, Tuulikki, additional, and Jokiranta, T. Sakari, additional

Published
2022
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46. Short interruptions of TNF-inhibitor treatment can be associated with treatment failure in patients with immune-mediated diseases

Author

Lamberg, Tea, Sipponen, Taina, Valtanen, Sanna, Eklund, Kari K, Mälkönen, Tarja, Aalto, Kristiina, Mikola, Katriina, Kolho, Kaija-Leena, Leinonen, Sanna, Isomäki, Pia, Mäkinen, Heidi, Vidqvist, Krista-Liisa, Kokko, Arto, Huilaja, Laura, Kyllönen, Minna, Keskitalo, Paula, Sard, Sirja, Vähäsalo, Paula, Koskela, Ritva, Kröger, Liisa, Lahtinen, Perttu, Haapala, Anna-Maija, Korkatti, Katja, Sokka-Isler, Tuulikki, and Jokiranta, T. Sakari

Abstract

The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment. This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases. Treatment interruptions were associated with immunisation in patients using infliximab (p < .001) or adalimumab (p < .000001). Patients with treatment interruptions were more likely to have been treated with more than one biological agent compared to those without treatment interruptions. This was particularly prominent among patients with a rheumatic disease (p < .00001). The most frequent reason for a treatment interruption among the cases was an infection, whereas among the control patients it was remission. The median length of one interruption was one month (interquartile range 1–3 months). Our results suggest that the interruptions of the treatment with TNF-inhibitors expose patients to immunisation and increase the need for drug switching. These findings stress the importance of careful judgement of the need for a short interruption in the biological treatment in clinical work, especially during non-severe infections.

Published
2022
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47. Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers

Author

FinnGen Rheumatology Clinical Expe, Palomaki, Antti, Palotie, Aarno, Koskela, Jukka, Eklund, Kari K., Pirinen, Matti, Ripatti, Samuli, Laitinen, Tarja, Mars, Nina, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, Complex Disease Genetics, HUS Helsinki and Uusimaa Hospital District, HUS Inflammation Center, Department of Medicine, Statistical and population genetics, Department of Mathematics and Statistics, Biostatistics Helsinki, Department of Public Health, and Samuli Olli Ripatti / Principal Investigator

Subjects
rheumatoid arthritis, pulmonary fibrosis, PULMONARY-FIBROSIS, 3121 General medicine, internal medicine and other clinical medicine, respiratory system, genetic, behavioral disciplines and activities, respiratory tract diseases, polymorphism
Abstract

Objectives To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant. Methods FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant. Results Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men. Conclusion Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD.

Published
2021

48. IL-17A and TNF synergistically drive expression of proinflammatory mediators in synovial fibroblasts via IκBζ-dependent induction of ELF3.

Author

Kouri, Vesa-Petteri, Olkkonen, Juri, Nurmi, Katariina, Peled, Nitai, Ainola, Mari, Mandelin, Jami, Nordström, Dan C, and Eklund, Kari K

Subjects
PROTEIN metabolism, PROTEINS, INTERLEUKINS, CELL culture, FIBROBLASTS, SMALL interfering RNA, DNA-binding proteins, TUMOR necrosis factors, MESSENGER RNA, RESEARCH funding, ARTHRITIS, EPITHELIAL cells, TRANSCRIPTION factors
Abstract

Objective IL-17A and TNF act in synergy to induce proinflammatory mediators in synovial fibroblasts thus contributing to diseases associated with chronic arthritis. Many of these factors are regulated by transcription factor E74-like factor-3 (ELF3). Therefore, we sought to investigate ELF3 as a downstream target of IL-17A and TNF signalling and to characterize its role in the molecular mechanism of synergy between IL-17A and TNF. Methods Regulation of ELF3 expression by IL-17A and TNF was studied in synovial fibroblasts of RA and OA patients and RA synovial explants. Signalling leading to ELF3 mRNA induction and the impact of ELF3 on the response to IL-17A and TNF were studied using siRNA, transient overexpression and signalling inhibitors in synovial fibroblasts and HEK293 cells. Results ELF3 was marginally affected by IL-17A or TNF alone, but their combination resulted in high and sustained expression. ELF3 expression was regulated by the nuclear factor-κB (NF-κB) pathway and CCAAT/enhancer-binding protein β (C/EBPβ), but its induction required synthesis of the NF-κB co-factor IκB (inhibitor of NF-κB) ζ. siRNA-mediated depletion of ELF3 attenuated the induction of cytokines and matrix metalloproteinases by the combination of IL-17A and TNF. Overexpression of ELF3 or IκBζ showed synergistic effect with TNF in upregulating expression of chemokine (C-C motif) ligand 8 (CCL8), and depletion of ELF3 abrogated CCL8 mRNA induction by the combination of IκBζ overexpression and TNF. Conclusion Altogether, our results establish ELF3 as an important mediator of the synergistic effect of IL-17A and TNF in synovial fibroblasts. The findings provide novel information of the pathogenic mechanisms of IL-17A in chronic arthritis and implicate ELF3 as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers

Author

Palomäki, Antti, Palotie, Aarno, Koskela, Jukka, Eklund, Kari K., Pirinen, Matti, Ripatti, Samuli, Laitinen, Tarja, Mars, Nina, Tampere University, and Department of General Administration

Subjects
3141 Health care science, respiratory system, 3121 Internal medicine, behavioral disciplines and activities, respiratory tract diseases
Abstract

Objectives: To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant. Methods: FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant. Results: Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men. Conclusion: Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD. publishedVersion

Published
2021

50. A Family With A20 Haploinsufficiency Presenting With Novel Clinical Manifestations and Challenges for Treatment

Author

Hautala, Timo, primary, Vähäsalo, Paula, additional, Kuismin, Outi, additional, Keskitalo, Salla, additional, Rajamäki, Kristiina, additional, Väänänen, Antti, additional, Simojoki, Marja, additional, Säily, Marjaana, additional, Pelkonen, Ilpo, additional, Tokola, Heikki, additional, Mäkinen, Markus, additional, Kaarteenaho, Riitta, additional, Jartti, Airi, additional, Hautala, Nina, additional, Kantola, Saara, additional, Jackson, Päivi, additional, Glumoff, Virpi, additional, Saarela, Janna, additional, Varjosalo, Markku, additional, Eklund, Kari K., additional, and Seppänen, Mikko R. J., additional

Published
2021
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