Browsing by Subject "REMISSION"

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  • NORD STAR Study Grp; Hetland, Merete Lund; Haavardsholm, Espen A.; Rudin, Anna; Nordström, Dan; van Vollenhoven, Ronald (2020)
    OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
  • Honkamäki, Jasmin; Hisinger-Mölkänen, Hanna; Ilmarinen, Pinja; Piirilä, Päivi; Tuomisto, Leena E.; Andersen, Heidi; Huhtala, Heini; Sovijärvi, Anssi; Backman, Helena; Lundbäck, Bo; Rönmark, Eva; Lehtimäki, Lauri; Kankaanranta, Hannu (2019)
    Background: Asthma is currently divided into different phenotypes, with age at onset as a relevant differentiating factor. In addition, asthma with onset in adulthood seems to have a poorer prognosis, but studies investigating age-specific incidence of asthma with a wide age span are scarce. Objective: To evaluate incidence of asthma diagnosis at different ages and differences between child- and adult-diagnosed asthma in a large population-based study, with gender-specific analyzes included. Methods: In 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland. After two reminders, 4173 (52.3%) subjects responded. Incidence rate of asthma was retrospectively estimated based on the reported age of asthma onset. Adult-diagnosed asthma was defined as a physician-diagnosis of asthma made at >= 18 years of age. Results: Among those with physician-diagnosed asthma, altogether, 63.7% of subjects, 58.4% of men and 67.8% of women, reported adult-diagnosed asthma. Incidence of asthma diagnosis was calculated in 10-year age groups and it peaked in young boys (0-9 years) and middle-aged women (40-49 years) and the average incidence rate during the examined period between 1946 and 2015 was 2.2/1000/year. Adult-diagnosed asthma became the dominant phenotype among those with physician-diagnosed asthma by age of 50 years and 38 years in men and women, respectively. Conclusions: Asthma is mainly diagnosed during adulthood and the incidence of asthma diagnosis peaks in middle-aged women. Asthma diagnosed in adulthood should be considered more in clinical practice and management guidelines.
  • Laakso, Sini M.; Myllynen, Chris; Strbian, Daniel; Atula, Sari (2021)
    Background: The effect of comorbidities on the prognosis of myasthenia gravis (MG) remains unclear. In particular, the role of other autoimmune diseases (AD) is controversial. Methods: In this retrospective single-center cohort study, we investigated 154 consecutive generalized thymectomized MG patients, with a mean follow-up time of 8.6 (+/- 5.0) years post-thymectomy. Comorbidities diagnosed at any timepoint were retrieved from medical records and Charlson comorbidity index (CCI) scores were calculated. Patients were categorized into subgroups MG alone (n = 45) and MG with any comorbidity (n = 109); the latter was further categorized into MG with other ADs (n = 33) and MG with non-AD comorbidities (n = 76). The endpoints analyzed were complete stable remission (CSR), minimal need for medications, and need for inhospital treatments. Results: CSR was more frequent in MG alone than in MG with any comorbidity group (26.7% vs 8.3%, p = 0.004). Minimal need for medication was reached more often in the MG alone than in the MG with non-AD comorbidities group (p = 0.047). Need for in-hospital treatments was lower in the MG alone group than in MG patients with any comorbidity (p = 0.046). Logistic regression analysis revealed that lower CCI scores increased the likelihood of CSR (p = 0.033). Lower CCI scores were more prevalent both in patients with minimal need for medication and in patients who did not need in-hospital treatments (p < 0.001). Conclusions: Patients with generalized MG and comorbidities have a poorer prognosis than patients with MG alone during almost 9 years follow-up after thymectomy. AD comorbidities appeared not to translate into a higher risk compared to other comorbidities.
  • Lauper, Kim; Mongin, Denis; Iannone, Florenzo; Kristianslund, Eirik K.; Kvien, Tore K.; Nordström, Dan C.; Pavelka, Karel; Pombo-Suarez, Manuel; Rotar, Ziga; Santos, Maria J.; Codreanu, Catalin; Lukina, Galina; Gale, Sara L.; John, Markus; Luder, Yves; Courvoisier, Delphine S.; Gabay, Cem (2020)
    Objectives To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs). Methods Patients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan–Meier and Cox models, and CDAI over time by mixed models. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were corrected for attrition. Results 6713 TNFi-combo, 3762 TNFi-mono, 646 TCZ-combo and 384 TCZ-mono were eligible. Crude median retention was 3.67 years (95%CI 3.41-3.83) for TNFi-combo, 4.14 (3.77-4.62) for TNFi-mono, 2.98 (2.76-3.34) for TCZ-combo and 3.63 years (3.34-5.03) for TCZ-mono. After adjustment for covariates, country and year of treatment initiation stratification, hazards of discontinuation were lower for TCZ-mono (0.60, 95% CI 0.52-0.69) and TCZ-combo (0.66, 95% CI 0.54-0.81) compared to TNFi-combo. Adjusted CDAI evolution was not significantly different between groups. CDAI LDA and remission corrected for attrition were similar between TCZ with or without csDMARDs and TNFi-combo. Conclusion In routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.
  • Nordic Study Grp Pediat Rheumatolo; Glerup, Mia; Thiel, Steffen; Rypdal, Veronika; Peltoniemi, Suvi; Aalto, Kristiina; Herlin, Troels (2019)
    Background To determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a population-based Nordic juvenile idiopathic arthritis (JIA) cohort. Additionally, to assess the predictive value of lectin pathway proteins with respect to remission status. Methods A population-based cohort study of consecutive cases of JIA with a disease onset from 1997 to 2000 from defined geographical areas of Finland, Sweden, Norway and Denmark with 17 years of follow-up was performed. Clinical characteristics were registered and H-ficolin, M-ficolin, MASP-1, MASP-3, MBL and CL-K1 levels in serum were analyzed. Results In total, 293 patients with JIA were included (mean age 23.7 +/- 4.4 years; mean follow-up 17.2 +/- 1.7 years). Concentrations of the lectin protein levels in serum were higher at baseline compared to the levels 17 years after disease onset (p
  • Holster, S.; Repsilber, D.; Geng, D.; Hyotylainen, T.; Salonen, A.; Lindqvist, C. M.; Rajan, S. K.; de Vos, W. M.; Brummer, R. J.; König, J. (2021)
    Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.
  • Auno, Sami; Lauronen, Leena; Wilenius, Juha; Peltola, Maria; Vanhatalo, Sampsa; Palva, Matias (2021)
    Objective: To examine the usability of long-range temporal correlations (LRTCs) in non-invasive localization of the epileptogenic zone (EZ) in refractory parietal lobe epilepsy (RPLE) patients. Methods: We analyzed 10 RPLE patients who had presurgical MEG and underwent epilepsy surgery. We quantified LRTCs with detrended fluctuation analysis (DFA) at four frequency bands for 200 cortical regions estimated using individual source models. We correlated individually the DFA maps to the distance from the resection area and from cortical locations of interictal epileptiform discharges (IEDs). Additionally, three clinical experts inspected the DFA maps to visually assess the most likely EZ locations. Results: The DFA maps correlated with the distance to resection area in patients with type II focal cortical dysplasia (FCD) (p < 0:05), but not in other etiologies. Similarly, the DFA maps correlated with the IED locations only in the FCD II patients. Visual analysis of the DFA maps showed high interobserver agreement and accuracy in FCD patients in assigning the affected hemisphere and lobe. Conclusions: Aberrant LRTCs correlate with the resection areas and IED locations. Significance: This methodological pilot study demonstrates the feasibility of approximating cortical LRTCs from MEG that may aid in the EZ localization and provide new non-invasive insight into the presurgical evaluation of epilepsy. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (
  • NEO-RACo Study Group; Rantalaiho, Vappu; Sandström, Tia; Koski, Juhani; Hannonen, Pekka; Mottonen, Timo; Kaipiainen-Seppänen, Oili; Yli-Kerttula, Timo; Kauppi, Markku J.; Uutela, Toini; Malmi, Timo; Julkunen, Heikki; Laasonen, Leena; Kautiainen, Hannu; Leirisalo-Repo, Marjatta (2019)
    Objective The short-term outcomes of remission-targeted treatments of rheumatoid arthritis (RA) are well-established, but the long-term success of such strategies is speculative, as is the role of early add-on biologics. We assessed the 10-year outcomes of patients with early RA treated with initial remission-targeted triple combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), 7.5-mg prednisolone, and additional infliximab (IFX) or placebo infusions. Methods Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARDs and prednisolone and randomized to double-blind receipt of infusions of either IFX (the Finnish Rheumatoid Arthritis Combination Therapy Trial [FIN-RACo] + IFX) or placebo (FIN-RACo + placebo) during the first 6 months. After 2 years, the treatment strategies became unrestricted, but the treatment goal was strict remission in the TNF-Blocking Therapy in Combination With Disease-Modifying Antirheumatic Drugs in Early Rheumatoid Arthritis (NEO-RACo) study. At 10 years, the clinical and radiographic outcomes and the drug treatments used between 5 and 10 years were assessed. Results Ninety patients (91%) were followed after 2 years, 43 in the FIN-RACo + IFX and 47 in the FIN-RACo + placebo group. At 10 years, the respective proportions of patients in strict NEO-RACo remission and in Disease Activity Score using 28 joints remission in the FIN-RACo + IFX and FIN-RACo + placebo groups were 46% and 38% (P = 0.46) and 82% and 72% (P = 0.29), respectively. The mean total Sharp/van der Heijde score was 9.8 in the FIN-RACo + IFX and 7.3 in the FIN-RACo + placebo group (P = 0.34). During the 10-year follow-up, 26% of the FIN-RACo + IFX group and 30% of the FIN-RACo + placebo group had received biologics (P = 0.74). Conclusion In early RA, excellent results can be maintained up until 10 years in most patients treated with initial combination csDMARDs and remission-targeted strategy, regardless of initial IFX/placebo infusions.
  • Ilander, Mette; Kreutzman, Anna; Rohon, Peter; Melo, Teresa; Faber, Edgar; Porkka, Kimmo; Vakkila, Jukka; Mustjoki, Satu (2014)
  • Jongsma, Maria M. E.; Vuijk, Stephanie A.; Cozijnsen, Martinus A.; van Pieterson, Merel; Norbruis, Obbe F.; Groeneweg, Michael; Wolters, Victorien M.; van Wering, Herbert M.; Hojsak, Iva; Kolho, Kaija-Leena; van Wijk, Michiel P.; Teklenburg-Roord, Sarah T. A.; de Meij, Tim G. J.; Escher, Johanna C.; de Ridder, Lissy (2022)
    To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the "TISKids" study assigned to the conventional treatment arm. Patients were aged 3-17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI)> 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10.
  • Laharie, David; Bourreille, Arnaud; Branche, Julien; Allez, Matthieu; Bouhnik, Yoram; Filippi, Jerome; Zerbib, Frank; Savoye, Guillaume; Vuitton, Lucine; Moreau, Jacques; Amiot, Aurelien; Beaugerie, Laurent; Ricart, Elena; Dewit, Olivier; Lopez-Sanroman, Antonio; Fumery, Mathurin; Carbonnel, Franck; Buisson, Anthony; Coffin, Benoit; Roblin, Xavier; van Assche, Gert; Esteve, Maria; Färkkilä, Martti; Gisbert, Javier P.; Marteau, Philippe; Nahon, Stephane; de Vos, Martine; Peyrin-Biroulet, Laurent; Mary, Jean-Yves (2021)
    BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.
  • Hanssen, Nordin M. J.; Vos de, Willem Meindert; Nieuwdorp, Max (2021)
    Fecal microbiota transplantation (FMT) is gaining considerable traction as a therapeutic approach to influence the course of a plethora of chronic conditions, ranging from metabolic syndrome and malignancies to auto-immune and neurological diseases, and helped to establish the contribution of the gut microbiome to these conditions. Although FMT procedures have yielded important mechanistic insights, their use in clinical practice may be limited due to practical objections in the setting of metabolic diseases. While its applicability is established to treat recurrent Clostridiodes difficile, FMT is emerging in ulcerative colitis and various other diseases. A particularly new insight is that FMTs may not only alter insulin sensitivity but may also alter the course of type 1 diabetes by attenuating underlying auto-immunity. In this review, we will outline the major principles and pitfalls of FMT and where optimization of study design and the procedure itself will further advance the field of cardiometabolic medicine.
  • Riihimaki, K.; Sintonen, H.; Vuorilehto, M.; Jylhä, P.; Saarni, S.; Isometsa, E. (2016)
    Background: Depressive disorders are known to impair health-related quality of life (HRQoL) both in the short and long term. However, the determinants of long-term HRQoL outcomes in primary care patients with depressive disorders remain unclear. Methods: In a primary care cohort study of patients with depressive disorders, 82% of 137 patients were prospectively followed up for five years. Psychiatric disorders were diagnosed with SCID-I/P and SCID-II interviews; clinical, psychosocial and socio-economic factors were investigated by rating scales and questionnaires plus medical and psychiatric records. HRQoL was measured with the generic 15D instrument at baseline and five years, and compared with an age-standardized general population sample (n = 3707) at five years. Results: Depression affected the 15D total score and almost all dimensions at both time points. At the end of follow-up, HRQoL of patients in major depressive episode (MDE) was particularly low, and the association between severity of depression (Beck Depression Inventory [BDI]) and HRQoL was very strong (r = -0.804). The most significant predictors for change in HRQoL were changes in BDI and Beck Anxiety Inventory (BAI) scores. The mean 15D score of depressive primary care patients at five years was much worse than in the age-standardized general population, reaching normal range only among patients who were in clinical remission and had virtually no symptoms. Conclusions: Among depressive primary care patients, presence of current depressive symptoms markedly reduces HRQoL, with symptoms of concurrent anxiety also having a marked impact. For HRQoL to normalize, current depressive and anxiety symptoms must be virtually absent. (C) 2016 Elsevier Masson SAS. All rights reserved.
  • Räisänen, Petri; Backman, Helena; Hedman, Linnea; Andersson, Martin; Stridsman, Caroline; Kankaanranta, Hannu; Ilmarinen, Pinja; Andersen, Heidi; Piirilä, Päivi; Lindberg, Anne; Lundback, Bo; Rönmark, Eva (2021)
    Background The prevalence of asthma has increased both among children and adults during the latter half of the 20th century. The prevalence among adults is affected by the incidence of asthma not only in childhood but also in adulthood. Time trends in asthma incidence have been poorly studied. Aims The aim of this study was to review the incidence of adult-onset asthma from 1996 to 2006 and 2006 to 2016 and compare the risk factor patterns. Methods In the Obstructive Lung Disease in Northern Sweden (OLIN) studies, two randomly selected population-based samples in the 20-69-year age group participated in postal questionnaire surveys about asthma in 1996 (n=7104, 85%) and 2006 (n=6165, 77%). A 10-year follow-up of the two cohorts with the same validated questionnaire was performed, and 5709 and 4552 responded, respectively. Different definitions of population at risk were used in the calculations of asthma incidence. The protocol followed a study performed between 1986 and 1996 in the same area. Results The crude incidence rate of physician-diagnosed asthma was 4.4 per 1000 person-years (men 3.8, women 5.5) from 1996 to 2006, and 4.8 per 1000 person-years (men 3.7, women 6.2) from 2006 to 2016. When correcting for possible under-diagnosis at study entry, the incidence rate was 2.4 per 1000 personyears from 1996 to 2006 and 2.6 per 1000 person-years from 2006 to 2016. The incidence rates were similar across age groups. Allergic rhino-conjunctivitis was the main risk factor for incident asthma in both observation periods (risk ratio 2.4-2.6). Conclusions The incidence of adult-onset asthma has been stable over the last two decades and has remained at a similar level since the 1980s. The high incidence contributes to the increase in asthma prevalence.
  • Laukkanen, S.; Gronroos, T.; Polonen, P.; Kuusanmaki, H.; Mehtonen, J.; Cloos, J.; Ossenkoppele, G.; Gjertsen, B.; Oystein, B.; Heckman, C.; Heinaniemi, M.; Kontro, M.; Lohi, O. (2017)
  • Canaani, Jonathan; Labopin, Myriam; Socie, Gerard; Nihtinen, Anne; Huynh, Anne; Cornelissen, Jan; Deconinck, Eric; Gedde-Dahl, Tobias; Forcade, Edouard; Chevallier, Patrice; Bourhis, Jean H.; Blaise, Didier; Mohty, Mohamad; Nagler, Arnon (2017)
    Up to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3-ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the European Society of Blood and Marrow Transplantation. A cohort of 357 patients with hyperleukocytosis (159 patients with white blood count [WBC] 50 K-100 K, 198 patients with WBC >= 100 K) was compared to 918 patients without hyperleukocytosis. Patients with hyperleukocytosis were younger, had an increased rate of favorable risk cytogenetics, and more likely to be FLT3 and NPM1 mutated. In multivariate analysis, hyperleukocytosis was independently associated with increased relapse incidence (hazard ratio [HR] of 1.55, 95% confidence interval [CI], 1.14-2.12; P = .004), decreased leukemia-free survival (HR of 1.38, 95% CI, 1.07-1.78; P = .013), and inferior overall survival (HR of 1.4, 95% CI, 1.07-1.84; P = .013). Hyperleukocytosis retains a significant prognostic role for AML patients undergoing HSCT.
  • Shimoni, Avichai; Labopin, Myriam; Savani, Bipin; Volin, Liisa; Ehninger, Gerhard; Kuball, Jurgen; Bunjes, Donald; Schaap, Nicolaas; Vigouroux, Stephane; Bacigalupo, Andrea; Veelken, Hendrik; Sierra, Jorge; Eder, Matthias; Niederwieser, Dietger; Mohty, Mohamad; Nagler, Arnon (2016)
    Background: Myeloablative (MAC) and reduced-intensity conditioning (RIC) are established approaches for allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML). Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years) and the pattern of late events following RIC due to the relative recent introduction of this approach. Methods: We analyzed long-term outcomes in a cohort of 1423 AML patients, age >= 50 years, after SCT from HLA-matched siblings, during the years 1997-2005, median follow-up 8.3 years (0.1-17). Results: The 10-year leukemia-free survival (LFS) was 31 % (95CI, 27-35) and 32 % (28-35) after MAC and RIC, respectively (P = 0.57). The 10-year GVHD/relapse-free survival (GRFS), a surrogate for quality of life was 22 % (18-25) and 21 % (18-24), respectively (P = 0.79). The 10-year non-relapse mortality (NRM) was higher and relapse rate was lower after MAC, throughout the early and late post-transplant course. The 10-year LFS among 584 patients surviving leukemia-free 2 years after SCT was 71 % (65-76) and 73 % (67-78) after MAC and RIC, respectively (P = 0.76). Advanced leukemia at SCT was the major predictor of LFS subsequent to the 2-year landmark. Relapse was the major cause of late death after both regimens; however, NRM and in particular chronic graft-versus-host disease and second cancers were more common causes of late death after MAC. Conclusions: Long-term LFS and GRFS are similar after RIC and MAC. Most events after RIC or MAC occur within the first 2 years after SCT. Patients who are leukemia-free 2 years after SCT can expect similar good subsequent outcome after both approaches.
  • the Nordic Study Group of Pediatric Rheumatology (NoSPeR); Glerup, Mia; Rypdal, Veronika; Arnstad, Ellen Dalen; Ekelund, Maria; Peltoniemi, Suvi; Aalto, Kristiina; Rygg, Marite; Toftedal, Peter; Nielsen, Susan; Fasth, Anders; Berntson, Lillemor; Nordal, Ellen; Herlin, Troels (2020)
    Objective The present study was undertaken to assess the long-term course, remission rate, and disease burden in juvenile idiopathic arthritis (JIA) 18 years after disease onset in a population-based setting from the early biologic era. Methods A total of 510 consecutive cases of JIA with disease onset between 1997 and 2000 from defined geographic regions in Denmark, Norway, Sweden, and Finland were prospectively included in this 18-year cohort study. At the follow-up visit, patient-reported demographic and clinical data were collected. Results The study included 434 (85%) of the 510 eligible JIA participants. The mean +/- SD age was 24.0 +/- 4.4 years. The median juvenile arthritis disease activity score in 71 joints (JADAS-71) was 1.5 (interquartile range [IQR] 0-5), with the enthesitis-related arthritis (ERA) category of JIA having the highest median score (4.5 [IQR 1.5-8.5], P = 0.003). In this cohort, 46% of patients still had active disease, and 66 (15%) were treated with synthetic disease-modifying antirheumatic drugs and 84 (19%) with biologics. Inactive disease indicated by a JADAS-71 score of Conclusion A substantial proportion of the JIA cohort did not achieve CR despite new treatment options during the study period. The ERA category showed the worst outcomes, and in general there is still a high burden of disease in adulthood for JIA.
  • Kolstad, Arne; Pedersen, Lone Bredo; Eskelund, Christian W.; Husby, Simon; Gronbaek, Kirsten; Jerkeman, Mats; Laurell, Anna; Räty, Riikka; Elonen, Erkki; Andersen, Niels Smedegaard; Brown, Peter deNully; Kimby, Eva; Bentzen, Hans; Sundstrom, Christer; Ehinger, Mats; Karjalainen-Lindsberg, Marja-Liisa; Delabie, Jan; Ralfkiaer, Elisabeth; Fagerli, Unn-Merete; Nilsson-Ehle, Herman; Lauritzsen, Grete Fossum; Kuittinen, Outi; Niemann, Carsten; Geisler, Christian Hartman; Nordic Lymphoma Grp (2017)
    The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin heavy chain gene (IgH) and clonal IgH rear-rangements. Significantly shorter progression-free survival (PFS) and overall survival (OS) was demonstrated for patients who were MRD positive pre-ASCT (54 patients) or in the first analysis post-ASCT (23 patients). The median PFS was only 20 months in those who were MRD-positive in the first sample post-ASCT, compared with 142 months in the MRD-negative group (P
  • Ornbjerg, Lykke M.; Linde, Louise; Georgiadis, Stylianos; Rasmussen, Simon H.; Lindström, Ulf; Askling, Johan; Michelsen, Brigitte; Di Giuseppe, Daniela; Wallman, Johan K.; Pavelka, Karel; Zavada, Jakub; Nissen, Michael J.; Jones, Gareth T.; Relas, Heikki; Pirila, Laura; Rotar, Ziga; Geirsson, Arni Jon; Gudbjornsson, Bjorn; Kristianslund, Eirik K.; Horst-Bruinsma, Irene Van Sder; Loft, Anne Gitte; Laas, Karin; Iannone, Florenzo; Corrado, Addolorata; Ciurea, Adrian; Santos, Maria J.; Santos, Helena; Codreanu, Catalin; Akkoc, Nurullah; Gunduz, Ozgul S.; Glintborg, Bente; Ostergaard, Mikkel; Hetland, Merete Lund (2022)
    Objectives: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. Methods: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. Results: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97-0.98), men vs. women: 1.88 (1.60-2.22), current vs. non-smoking: 0.76 (0.63-0.91), HLA-B27 positive vs. negative: 1.51 (1.20-1.91), TNF start year 2015-2018 vs. 2009-2014: 1.24 (1.06-1.45), CRP > 10 vs.