Browsing by Subject "Rheumatoid arthritis"

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  • Relas, Heikki; Kosola, Silja (2019)
    ObjectivesAcross diagnosis groups, transition of adolescents and young adults from children's hospitals to adult care associates with decreased treatment adherence and suboptimal treatment results. Our aim was to compare the health-related quality of life (HRQoL) and disease activity of juvenile idiopathic arthritis (JIA) patients after the transfer of care to the adult clinic and adult patients in the same outpatient clinic.MethodsAll consecutive JIA patients aged 16 to 20years who visited the transition clinic between September 2016 and August 2017 and all consecutive adult onset arthritis patients between December 2016 and August 2017 in the rheumatology outpatient clinic of Helsinki University Hospital were evaluated. HRQoL was measured by a generic instrument, 15D.ResultsA total of 291 patients, 130 JIA, and 161 adults were identified with respective median disease durations of 6.5 and 4.0years. Adults had lower HRQoL measured by 15D (median 0.90 vs. 0.96, P
  • Kuuliala, Krista; Kuuliala, Antti; Koivuniemi, Riitta; Kautiainen, Hannu; Repo, Heikki; Leirisalo-Repo, Marjatta (BioMed Central, 2017)
    Abstract Background We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4+ T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA. Methods Thirty-five DMARD-naïve patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes. Treatment response was determined after 1 year of treatment with synthetic DMARDs, with remission defined as absence of tender and swollen joints and normal erythrocyte sedimentation rate. Exact logistic regression was used to investigate the association of baseline variables with treatment response. Ninety-five percent CIs of means were estimated by bias-corrected bootstrapping. Results High JAK3 phosphorylation in CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes and low JAK2 phosphorylation in CD14+ monocytes were significantly associated with remission following treatment with synthetic DMARDs. Conclusions Baseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict treatment response achieved by synthetic DMARDs among patients with early RA.
  • Kuuliala, Krista; Kuuliala, Antti; Koivuniemi, Riitta; Kautiainen, Hannu; Repo, Heikki; Leirisalo-Repo, Marjatta (2017)
    Background: We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4(+) T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA. Methods: Thirty-five DMARD-naive patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes. Treatment response was determined after 1 year of treatment with synthetic DMARDs, with remission defined as absence of tender and swollen joints and normal erythrocyte sedimentation rate. Exact logistic regression was used to investigate the association of baseline variables with treatment response. Ninety-five percent CIs of means were estimated by bias-corrected bootstrapping. Results: High JAK3 phosphorylation in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes and low JAK2 phosphorylation in CD14(+) monocytes were significantly associated with remission following treatment with synthetic DMARDs. Conclusions: Baseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict treatment response achieved by synthetic DMARDs among patients with early RA.
  • 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.
  • Mustonen, Anne-Mari; Käkelä, Reijo; Lehenkari, Petri; Huhtakangas, Johanna; Turunen, Sanna; Joukainen, Antti; Kaariainen, Tommi; Paakkonen, Tommi; Kroger, Heikki; Nieminen, Petteri (2019)
    Background: Infrapatellar fat pad (IFP) has recently emerged as a potential source of inflammation in knee arthropathies. It has been proposed to be one source of adipocytokines, fatty acids (FA), and FA-derived lipid mediators that could contribute to the pathophysiological processes in the knee joint. Alterations in synovial fluid (SF) lipid composition have been linked to both osteoarthritis (OA) and rheumatoid arthritis (RA). The aim of the present study was to compare the FA signatures in the IFP and SF of RA and OA patients. Methods: Pairs of IFP and SF samples were collected from the same knees of RA (n=10) and OA patients (n=10) undergoing total joint replacement surgery. Control SF samples (n=6) were harvested during diagnostic or therapeutic arthroscopic knee surgery unrelated to RA or OA. The FA composition in the total lipids of IFP and SF was determined by gas chromatography with flame ionization and mass spectrometric detection. Results: Arthropathies resulted in a significant reduction in the SF proportions of n-6 polyunsaturated FA (PUFA), more pronouncedly in OA than in RA. OA was also characterized with reduced percentages of 22:6n-3 and lower product/precursor ratios of n-3 PUFA. The proportions of total monounsaturated FA increased in both RA and OA SF. Regarding IFP, RA patients had lower proportions of 20:4n-6, total n-6 PUFA, and 22:6n-3, as well as lower product/precursor ratios of n-3 PUFA compared to OA patients. The average chain length of SF FA decreased in both diagnoses and the double bond index in OA. Conclusions: The observed complex alterations in the FA signatures could have both contributed to but also limited the inflammatory processes and cartilage destruction in the RA and OA knees.
  • Mustonen, Anne-Mari; Käkelä, Reijo; Lehenkari, Petri; Huhtakangas, Johanna; Turunen, Sanna; Joukainen, Antti; Kääriäinen, Tommi; Paakkonen, Tommi; Kröger, Heikki; Nieminen, Petteri (BioMed Central, 2019)
    Abstract Background Infrapatellar fat pad (IFP) has recently emerged as a potential source of inflammation in knee arthropathies. It has been proposed to be one source of adipocytokines, fatty acids (FA), and FA-derived lipid mediators that could contribute to the pathophysiological processes in the knee joint. Alterations in synovial fluid (SF) lipid composition have been linked to both osteoarthritis (OA) and rheumatoid arthritis (RA). The aim of the present study was to compare the FA signatures in the IFP and SF of RA and OA patients. Methods Pairs of IFP and SF samples were collected from the same knees of RA (n = 10) and OA patients (n = 10) undergoing total joint replacement surgery. Control SF samples (n = 6) were harvested during diagnostic or therapeutic arthroscopic knee surgery unrelated to RA or OA. The FA composition in the total lipids of IFP and SF was determined by gas chromatography with flame ionization and mass spectrometric detection. Results Arthropathies resulted in a significant reduction in the SF proportions of n-6 polyunsaturated FA (PUFA), more pronouncedly in OA than in RA. OA was also characterized with reduced percentages of 22:6n-3 and lower product/precursor ratios of n-3 PUFA. The proportions of total monounsaturated FA increased in both RA and OA SF. Regarding IFP, RA patients had lower proportions of 20:4n-6, total n-6 PUFA, and 22:6n-3, as well as lower product/precursor ratios of n-3 PUFA compared to OA patients. The average chain length of SF FA decreased in both diagnoses and the double bond index in OA. Conclusions The observed complex alterations in the FA signatures could have both contributed to but also limited the inflammatory processes and cartilage destruction in the RA and OA knees.
  • Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny; Lukina, Galina; Hetland, Merete Lund; Tarp, Ulrik; Ancuta, Ioan; Pavelka, Karel; Nordstrom, Dan C.; Gabay, Cem; Canhao, Helene; Tomsic, Matija; van Riel, Piet L. C. M.; Gomez-Reino, Juan; Kvien, Tore K.; van Vollenhoven, Ronald F.; Rheumatic Dis Portuguese Register (2016)
    Background: The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg x 2, but some data have suggested similar clinical efficacy with 500 mg x 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course. Methods: Twelve European registries participating in the CERERRA collaboration (The European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) submitted anonymized datasets with demographic, efficacy and treatment data for patients who had started RTX. Treatment effectiveness was assessed by DAS28 reductions and EULAR responses after 6 months. Results: Data on RTX dose were available for 2,873 patients, of whom 2,625 (91.4 %) and 248 (8.6 %) received 1000 mg x 2 and 500 mg x 2, respectively. Patients treated with 500 mg x 2 were significantly older, had longer disease duration, higher number of prior DMARDs, but lower number of prior biologics and lower baseline DAS28 than those treated with 1000 mg x 2. Fewer patients in the low-dose group received concomitant DMARDs but more frequently received concomitant corticosteroids. Both doses led to significant clinical improvements at 6 months. DAS28 reductions at 6 months were comparable in the 2 dose regimens [mean DeltaDAS28 +/- SD -2.0 +/- 1.3 (high dose) vs. -1.7 +/- 1.4 (low dose), p = 0.23 adjusted for baseline differences]. Similar percentages of patients achieved EULAR good response in the two dose groups, 18.4 % vs. 17.3 %, respectively (p = 0.36). Conclusions: In this large observational cohort initial treatment with RTX at 500 mg x 2 and 1000 mg x 2 led to comparable clinical outcomes at 6 months.
  • Muilu, Paula; Rantalaiho, Vappu; Kautiainen, Hannu; Virta, Lauri J; Eriksson, Johan G; Puolakka, Kari (BioMed Central, 2020)
    Abstract Background In this retrospective cohort study, we evaluated the drug therapies used for early rheumatoid (RA) and undifferentiated (UA) arthritis patients. Methods From a nationwide register maintained by the Social Insurance Institution, information on sex, date of birth, and date of special medicine reimbursement decision for all new Finnish RA and UA patients between 2011 and 14 were collected, and their DMARD (Disease Modifying Antirheumatic Drug) purchases during the first year after the diagnosis were analyzed. Results A total of 7338 patients with early RA (67.3% female, 68.1% seropositive) and 2433 with early UA (67.8% female) were identified. DMARDs were initiated during the first month after the diagnosis to 92.0% of the patients with seropositive RA, 90.3% with seronegative RA and to 87.7% with UA (p < 0.001). Respectively, 72.1, 63.4, and 42.9% of the patients (p < 0.001) purchased methotrexate; 49.8, 35.9, and 16.0% (p < 0.001) as part of a DMARD combination during the first month. By the end of the first year after the diagnosis, self-injected biologics were purchased by 2.6, 5.3 and 3.1% (p < 0.001) of them. Only 1.4, 2.6 and 3.0% (p < 0.001) of the patients were not receiving any DMARDs. During the first year, 83.4% of the seropositive RA patients had purchased methotrexate, 50.4% sulfasalazine, 72.1% hydroxychloroquine, and 72.6% prednisolone. Conclusions Currently, combination therapy including methotrexate is a common treatment strategy for early seropositive RA in Finland. Despite an easy access to biologics, these drugs are seldom needed during the first year after diagnosis.
  • Glinatsi, Daniel; Heiberg, Marte S.; Rudin, Anna; Nordstrom, Dan; Haavardsholm, Espen A.; Gudbjornsson, Bjorn; Ostergaard, Mikkel; Uhlig, Till; Grondal, Gerdur; Horslev-Petersen, Kim; van Vollenhoven, Ronald; Hetland, Merete L. (2017)
    Background: New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis (RA). However, it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can be maintained with conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy, and whether they differ in efficacy and safety. The Nordic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) study will assess and compare (1) the proportion of patients who achieve remission in a head-to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. Methods/design: In a pragmatic, 80-160-week, multicenter, randomized, open-label, assessor-blinded, phase 4 study, 800 patients with early RA (symptom duration less than 24 months) are randomized 1: 1: 1: 1 to one of four different treatment arms: (1) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i. a. glucocorticoids (arm 1A) or methotrexate + prednisolone p.o. (arm 1B), (2) methotrexate + certolizumab-pegol, (3) methotrexate + abatacept, or (4) methotrexate + tocilizumab. The primary clinical endpoint is the proportion of patients reaching Clinical Disease Activity Index (CDAI) remission at week 24. Patients in stable remission over 24 consecutive weeks enter part 2 of the study earliest after 48 weeks. Patients not achieving sustained CDAI remission over 24 consecutive weeks, exit the study after 80 weeks. In part 2, patients are re-randomized to two different de-escalation strategies, either immediate or delayed (after 24 weeks) tapering, followed by cessation of study medication. All patients remain on stable doses of methotrexate. The primary clinical endpoint in part 2 is the proportion of patients in remission (CDAI Discussion: NORD-STAR is the first investigator-initiated, randomized, early RA trial to compare (1) csDMARD and three different bDMARD therapies head to head and (2) two different de-escalation strategies. The trial has the potential to identify which treatment strategy to apply in early RA to achieve the best possible outcomes for both patients and society.
  • NEO-RACo Study Grp (2018)
    Adverse events (AEs) are common during disease-modifying antirheumatic drug (DMARD) treatment, but their influence on treatment results is unclear. We studied AEs in relation to disease activity in early rheumatoid arthritis (RA). Ninety-nine patients started intensive treatment with three conventional synthetic DMARDs (csDMARDs) and oral prednisolone, and were randomized to a 6-month induction treatment with infliximab or placebo. All AEs during the first 12 months of treatment were recorded. We scored each AE based on severity (scale 1-4) and defined the burden of AEs as the sum of these scores. Patients were divided into tertiles according to the burden of AEs. As outcomes, we assessed 28-joint disease activity score (DAS28) levels and remission rates at 12 and 24 months. Three hundred thirty-one AEs in 99 patients were reported, and 27 (8%) were categorized as severe or serious. Mean burden of AEs per patient was 5.4 +/- 4.3. Seventy-nine AEs (24%) led to temporary (n = 52) or permanent (n = 27) csDMARD discontinuation. Of discontinuations, 1, 21, and 57 were detected in the first, second, and third tertiles, respectively. DAS28 remission rates decreased across tertiles at 12 months (94, 94, and 76%; p for linearity 0.029) and at 24 months (90, 86, and 70%; p for linearity 0.021). Mean DAS28 levels increased across tertiles at 12 months (1.5 +/- 1.0, 1.7 +/- 0.9, and 1.9 +/- 1.2; p for linearity 0.021) and at 24 months (1.4 +/- 0.8, 1.6 +/- 1.0, and 1.9 +/- 1.1; p for linearity 0.007). High burden of AEs is associated with higher disease activity and lower likelihood of remission in early RA.
  • Alfat, Bamo (Helsingin yliopisto, 2019)
    Parodontiitti eli hampaiden tuki- ja kiinnityskudossairaus ja nivelreuma ovat molemmat kroonisia tulehdussairauksia, joiden patologiset taudinkulut muistuttavat vahvasti toisiaan. Tämän tutkielman tarkoituksena oli selvittää, kuinka nivelreuman hoitoon käytetyt biologiset lääkeainehoidot tehoavat samanaikaisesti potilaiden parodontiumiin ja mahdollisesti biofilmi välitteiseen parodontiittiin. Uudet spesifisesti vaikuttavat monoklonaalliset vasta-aineet ovat tuoneet moderniin lääketieteeseen tehokkaat ja tarkasti toimivat tavat hoitaa potilaiden monimuotoisia sairauksia. Nivelreuman sekä parodontiitin samantapaiset patogeeniset, etiologiat, yhteiskunnallisesti kalliit hoidot ja sairauksien vahvat yhteydet toisiinsa ovat isoja tekijöitä sille, miksi sairauksien yhtaikaista lääkehoitamista olisi syytä tutkia. Proinflammatoriset TNF-alfa-, IL-6- ja IL-1-sytokiinit ovat todistetusti osoittaneet isot roolinsa molempien tulehduksellisten sairauksien patologisissa prosesseissa. Täten esille nouseekin kysymys, että kuinka systeemisesti toteutetut biologiset lääkehoidot vastaavat sairauksien hoitoon. Lääkehoitojen kalliiden kulujen takia olisi järkevää ja yhteiskunnallisesti kannattavaa hyödyntää kyseisiä lääkeainehoitoja tehokkaan kohdistetusti sellaisille potilasryhmille, jotka hyötyisivät niistä kaikkein eniten. Näin potilaiden hoitomyöntyvyydet pitkille sekä raskaille hoidoille lisääntyisivät sekä tautien komplikaatioriskit vähentyisivät. Kaiken kaikkiaan pitkittäisprospektiiviset potilastutkimukset osoittivat tilastollisesti merkittäviä parannuksia nivelreumapotilaiden reumatologisissa - sekä parodontaallisissa parametreissa. Lääkeainehoidot osoittivat tehonsa nopeasti ja olivat muihin immunosuppressiivisiin lääkehoitoihin verrattuna tehokkaampia sekä paremmin siedettyjä. Täten biologiset lääkehoidot voisivat mahdollisesti tulevaisuudessa toimia osana parodontiitin hoitoa. Positiivisista tuloksista huolimatta on kuitenkin hyvä sanoa, että mittavampia tutkimuksia aiheesta tarvitaan lisää.
  • Ramos-Remus, Cesar; Barajas-Ochoa, Aldo; Ramirez-Gomez, Andrea; Castillo-Ortiz, Jose D.; Brambila-Barba, Victor; Adebajo, Adewale O.; Espinoza, Luis R.; Aceves-Avila, Francisco J.; Sanchez-Gonzalez, Jorge M.; Boudersa, Nadia; Slimani, Samy; Ladjouze-Rezig, Aicha; Diaz, Monica P.; Kirmayr, Karin I.; Asnal, Cecilia A.; Catoggio, Luis J.; Citera, Gustavo; Casado, Gustavo C.; Alvarez, Analia P.; Pisoni, Cecilia N.; Benavente, Emilio; Lopez-Cabanillas, Adriana; Baez, Roberto M.; Pons-Estel, Bernardo A.; Sacnun, Monica P.; Cavallasca, Javier A.; Paniego, Raul H.; Proudman, Susanna M.; Thomas, Ranjeny; Major, Gabor; Mathers, David M.; Schrieber, Leslie; Islam, Nazrul; Haq, Syed A.; Dessein, Patrick H.; von Muhlen, Carlos A.; Bianchi, Washington A.; Castelar-Pinheiro, Geraldo da R.; Feldman-Pollak, Daniel; Cossermelli, Waldenise; Bonfiglioli, Karina R.; Giorgi, Rina D.; Zabsonre-Tiendrebeogo, Wendlassida J.; Olaru, Lilia; Karsh, Jacob; Castro-Esparza, Irene H.; Fuentealba, Carlos; Aguilera, Sergio; Burgos, Paula I.; Leirisalo-Repo, Marjatta; GEO-RA Grp (2017)
    The age of onset of rheumatoid arthritis (RA) is an important outcome predictor. Northern countries report an age of RA onset of around 50 years, but apparently, variability exists across different geographical regions. The objective of the present study is to assess whether the age of onset of RA varies across latitudes worldwide. In a proof-of-concept cross-sectional worldwide survey, rheumatologists from preselected cities interviewed 20 consecutive RA patients regarding the date of RA onset (RAO, when the patient first noted a swollen joint). Other studied variables included location of each city, rheumatologist settings, latitudes (10A degrees increments, south to north), longitudes (three regions), intracountry consistency, and countries' Inequality-adjusted Human Development Index (IHDI). Data from 2481 patients (82% females) were obtained from 126 rheumatologists in 77 cities of 41 countries. Worldwide mean age of RAO was 44 +/- 14 years (95% CI 44-45). In 28% of patients, RA began before age 36 years and before age 46 years in 50% of patients. RAO was 8 years earlier around the Tropic of Cancer when compared with northern latitudes (p <0.001, 95% CI 3.5-13). Multivariate analysis showed that females, western cities, and latitudes around the Tropic of Cancer are associated with younger age of RAO (R (2) 0.045, p <0.001). A positive correlation was found between the age of RAO and IHDI (r = 0.7, p <0.01, R (2) 0.5). RA often begins at an early age and onset varies across latitudes worldwide. We postulate that countries' developmental status and their geographical and geomagnetic location influence the age of RAO.
  • Gudelj, Ivan; Salo, Perttu P.; Trbojevic-Akmacic, Irena; Albers, Malena; Primorac, Dragan; Perola, Markus; Lauc, Gordan (2018)
    Antibodies are known to have an important role in the development of rheumatoid arthritis (RA), one of the most prevalent chronic inflammatory diseases which primarily involves the joints. Most RA patients develop auto antibodies against immunoglobulin G (IgG) and changes in IgG glycosylation have been associated with RA. We undertook this study to determine whether altered IgG glycosylation precedes the disease diagnosis. We studied IgG glycosylation in RA in two prospective cohorts (N = 14,749) by measuring 28 IgG glycan traits in 179 subjects who developed RA within 10-years follow-up and 358 matched controls. Ultra-performance liquid chromatography method based on hydrophilic interactions (HILIC-UPLC) was used to analyse IgG glycans. Future RA diagnosis associated with traits related to lower galactosylation and sialylation of IgG when comparing the cases to the matched controls. In RA cases, these traits did not correlate with the time between being recruited to the study and being diagnosed with RA (median time 4.31 years). The difference in IgG glycosylation was relatively stable and present years before diagnosis. This indicates that long-acting factors affecting IgG glycome composition are among the underlying mechanisms of RA and that decreased galactosylation is a preexisting risk factor involved in the disease development.
  • Soini, Erkki; Asseburg, Christian; Taiha, Maarit; Puolakka, Kari; Purcaru, Oana; Luosujärvi, Riitta (2017)
    To model the American College of Rheumatology (ACR) outcomes, cost-effectiveness, and budget impact of certolizumab pegol (CZP) (with and without a hypothetical risk-sharing scheme at treatment initiation for biologic-na <ve patients) versus the current mix of reimbursed biologics for treatment of moderate-to-severe rheumatoid arthritis (RA) in Finland. A probabilistic model with 12-week cycles and a societal approach was developed for the years 2015-2019, accounting for differences in ACR responses (meta-analysis), mortality, and persistence. The risk-sharing scheme included a treatment switch and refund of the costs associated with CZP acquisition if patients failed to achieve ACR20 response at week 12. For the current treatment mix, ACR20 at week 24 determined treatment continuation. Quality-adjusted life years were derived on the basis of the Health Utilities Index. In the Finnish target population, CZP treatment with a risk-sharing scheme led to a estimated annual net expenditure decrease ranging from 1.7% in 2015 to 5.6% in 2019 compared with the current treatment mix. Per patient over the 5 years, CZP risk sharing was estimated to decrease the time without ACR response by 5%-units, decrease work absenteeism by 24 days, and increase the time with ACR20, ACR50, and ACR70 responses by 5%-, 6%-, and 1%-units, respectively, with a gain of 0.03 quality-adjusted life years. The modeled risk-sharing scheme showed reduced costs of a,notsign7866 per patient, with a more than 95% probability of cost-effectiveness when compared with the current treatment mix. The present analysis estimated that CZP, with or without the risk-sharing scheme, is a cost-effective alternative treatment for RA patients in Finland. The surplus provided by the CZP risk-sharing scheme could fund treatment for 6% more Finnish RA patients.
  • Kuusalo, Laura; Puolakka, Kari; Kautiainen, Hannu; Karjalainen, Anna; Malmi, Timo; Yli-Kerttula, Timo; Leirisalo-Repo, Marjatta; Rantalaiho, Vappu; NEO-RACo Study Grp (2017)
    Identifying prognostic factors for remission in early rheumatoid arthritis (ERA) patients is of key clinical importance. We studied patient-reported outcomes (PROs) as predictors of remission in a clinical trial. We randomized 99 untreated ERA patients to receive remission-targeted treatment with three disease-modifying antirheumatic drugs and prednisolone for 24 months, and infliximab or placebo for the initial 6 months. At baseline, we measured following PROs: eight Short Form 36 questionnaire (SF-36) dimensions, patient's global assessment [PGA, visual analogue scale (VAS)], Health Assessment Questionnaire (HAQ), and pain VAS. We used multivariable-adjusted regression models to identify PROs that independently predicted modified American College of Rheumatology remission at 2 years. Follow-up data at 2 years were available for 93 patients (92%), and 58 patients (62%) were in remission. At baseline, patients who achieved remission had higher radiological score (p = 0.04), lower tender joint count (p = 0.001), lower PGA (p = 0.005) and physician's global assessment (p = 0.019), lower HAQ (p = 0.016), less morning stiffness (p = 0.009), and significantly higher scores in seven out of eight SF-36 dimensions compared with patients who did not. In multivariable models that included all PROs, remission was associated with SF-36 dimensions higher vitality (odds ratio 2.01; 95% confidence interval 1.19-3.39) and better emotional role functioning (odds ratio 1.64; 95% confidence interval 1.01-2.68). PGA, pain VAS, HAQ, and other SF-36 dimensions were not associated with remission. We conclude that self-reported vitality and better emotional role functioning are among the most important PROs for the prediction of remission in ERA.
  • Hirvonen, H.; Kautiainen, H.; Moilanen, E.; Mikkelsson, M.; Leirisalo-Repo, M. (2017)
    Patients with rheumatoid arthritis (RA) have increased oxidative stress, decreased antioxidant levels, and impaired antioxidant capacity. Cold treatments are used to relieve joint inflammation and pain. Therefore, we measured the effect of cold treatments on the antioxidative capacity of RA patients with active disease. Sixty patients were randomized to (1) whole body cryotherapy at -110 A degrees C, (2) whole body cryotherapy at -60 A degrees C, or (3) local cryotherapy. Each treatment was given three times daily for 7 consecutive days in addition to the conventional rehabilitation. Blinded rheumatologist evaluated disease activity before the first and after the last cryotherapy. We collected plasma samples daily immediately before the first and after the second cryotherapy and measured total peroxyl radical trapping antioxidant capacity of plasma (TRAP), which reflects global combined antioxidant capacity of all individual antioxidants in plasma. Baseline morning TRAP levels (mean, 95% CI), adjusted for age, body mass index, disease activity, and dose of prednisolone, were 1244 (1098-1391) A mu M/l in the local cryotherapy, 1133 (1022-1245) A mu M/l in the cryotherapy at -60 A degrees C, and 989 (895-1082) A mu M/l in the cryotherapy at -110 A degrees C groups (p = 0.006). After the first treatment, there was a rise in 1-h TRAP of 14.2 (-4.2 to 32.6) A mu M/l, 16.1 (-7.4 to 39.6) A mu M/l, and 23.6 (4.1-43.2) A mu M/l, respectively. The increase was significant in the whole-body cryotherapy -110 A degrees C group (p <0.001) but not significant between the groups (p = 0.78). When analyzed for the whole week, the daily morning TRAP values differed significantly between the treatment groups (p = 0.021), but there was no significant change within each treatment group. Whole-body cryotherapy at -110 A degrees C induced a short-term increase in TRAP during the first treatment session with but not during other treatment modalities. The effect was short and the cold treatments did not cause a significant oxidative stress or adaptation during 1 week.