Cytokine Signalling Forum

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October 18

Aktif Romatoid Artritli Hastalarda Tofacitinib ve Baricitinib'in Etkinlik ve Güvenliliğinin Karşılaştırılması: Randomize Kontrollü Çalışmaların Bayes Network Meta-Analizi

Bae SC and Lee YH.
Z Rheumatol. 2018 Sep 6. DOI 10.1007/s00393-018-0531-5

Tofacitinib (TOF) 10mg and baricitinib (BARI) 4mg, in combination with methotrexate (MTX), were the most efficacious treatments in RA patients with an inadequate response to DMARDs or biologics. Both combination treatments presented acceptable safety profiles and were not associated with a significant risk of serious adverse events. This study employed a Bayesian approach to Meta-Analysis; combining the available evidence across a network of Randomised Controlled trials (RCTs). Twelve RCTs cont...

Keywords: JAK, Tofacitinib, Clinical, Phase 3

Translated by: Toz

Sürekli Hastalık Kontrolü Sağlanan Romatoid Artritli Hastalarda Baricitinib Dozunun Azaltılması: Prospektif Bir Çalışmanın Sonuçları

Takeuchi T, Genovese MC, Haraoui B, Li Z, Xie L, Klar R, Pinto Correia A, Otawa S, Lopez-Romero P, de la Torre I, Rooney TP, Smolen JS.
Ann Rheum Dis. 2019 Feb;78(2):171-178. DOI 10.1136/annrheumdis-2018-213271

In active RA patients, with an inadequate response (IR) to DMARDs who achieve low disease activity (LDA) following baricitinib (BARI) 4 mg treatment, disease control is better maintained with continued BARI 4 mg compared to tapering to 2 mg. The objective of this study was to investigate the effect of BARI tapering in patients achieving sustained disease control with BARI 4 mg. In the long-term extension study RA-BEYOND, patients receiving BARI 4 mg who achieved sustained LDA or remission at two...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Translated by: Toz

Aktif Romatoid Artritli Hastalarda Medyan 2 Yıldan Fazla Sürede Barisitinib'in Güvenliliği

Smolen J, Genovese M, Takeuchi T, Hyslop D, Macias W, Rooney T, Chen L, Dickson C, Riddle Camp J, Cardillo T, Ishii T and Winthrop K.
J Rheumatol. 2019 Jan;46(1):7-18. DOI: 10.3899/jrheum.171361

Baricitinib (BARI) showed an acceptable 5.5-year safety profile in this integrated analysis of patients with moderate-to-severe, active RA. This study evaluated the safety profile of the oral, once daily Janus kinase inhibitor, BARI, in adults with moderately to severely active RA. Data from eight randomised clinical trials and one long-term extension study were pooled and analysed for placebo comparison and dose response. There were 3492 patients who received BARI for a total of 6637 patient-y...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Translated by: Toz

August 18

Yalnız Tocilizumab veya Tocilizumab ve Metotreksat Kombinasyonu ile Tedavi Edilen Romatoid Artritli Hastalarda Remisyona Ulaştıktan Sonra Tocilizumabın Kesilmesi: Prospektif Randomize Kontrollü Çalışmadan Sonuçlar (SURPRISE çalışmasının ikinci yılından)

Kaneko Y, Kato M, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, Miyata M, Murakawa Y, Yasuoka H, Hirata S, Tanaka E, Miyasaka N, Yamanaka H, Yamamoto K, Takeuchi T, the SURPRISE study group.
Ann Rheum Dis 2018; 77:1268–1275 DOI: 10.1093/rheumatology/key121

The second-year results from the SURPRISE study show that low disease activity (LDA) can be maintained after discontinuation of tocilizumab with continued methotrexate after remission is achieved. Discontinuation of biologic agents in patients who have achieved remission or low disease activity (LDA) is desirable from a risk–benefit point of view. Compared with TNF inhibitors, little is known regarding TCZ-free remission or LDA, but studies indicate that only a small proportion of patien...

Keywords: IL-6, Tocilizumab, Clinical, Efficacy

Translated by: Toz

July 18

Hastalık Modifiye Edici Biyolojik Anti-Romatizmal İlaçlara Dirençli Aktif Romatoid Artritli Hastalarında Upadacitinib'ın Etkinliği ve Güvenliği (SELECT-BEYOND): Çift Kör, Randomize Kontrollü, Faz 3 Çalışma

Genovese MC, Fleischmann R, Combe B, Hall S, Rubbert-Roth A, Zhang Y, Zhou Y, Mohamed M-EF, Meerwein S, Pangan AL.
Lancet 2018;391:2513–24

Upadacitinib (UPA) extended release formulation was effective in treating patients with moderate-to-severe RA with an inadequate response to bDMARDs. Phase 2 study data has shown that UPA is an efficacious and safe treatment for active RA.1,2 SELECT-BEYOND was a double-blind, long-term extension, Phase 3 study to assess the efficacy of UPA in patients with RA who were bDMARD-IR. The first 12-weeks of SELECT-BEYOND were placebo-controlled, with a double-blind period followed by an ongoing double...

Keywords: JAK, Upadacitinib, Clinical, Phase 3

Translated by: Toz

Hastalığı Modifiye Edici Konvansiyonel Sentetik Anti-Romatizmal İlaçlara Yetersiz Yanıtlı Romatoid Artritli Hastalarında Upadacitinib Etkinliği ve Güvenliği (SELECT-NEXT): Randomize, Çift Kör, Plasebo Kontrollü Faz 3 Çalışma

Burmester GR, Kremer JM, Van den Bosch F, Kivitz A, Bessette L, Li Y, Zhou Y, Othman AA, Pangan AL, Camp HS.
Lancet 2018;391:2503–12

Patients with moderate-to-severe active RA had significant improvements in clinical signs and symptoms with upadacitinib (UPA) compared with placebo. In Phase 2 studies, UPA showed favourable efficacy when administered twice daily as an immediate-release formulation at doses of 6–12 mg in patients with active RA who had TNFi-IR.1,2 An extended-release formulation allowing once-daily (QD) administration was developed for Phase 3 studies. SELECT-NEXT was a double-blind, multicentre, Phase 3...

Keywords: JAK, Upadacitinib, Clinical, Phase 3

Translated by: Toz

June 18

Konvansiyonel Sentetik Hastalık Modifiye Edici Antiromatizmal İlaçlara Yetersiz Yanıtlı Romatoid Artritli Hastalarda Baricitinibin 1.yılında Yapısal Eklem Hasarının Radyografik Progresyonu Üzerine Olan Etkileri

van der Heijde D, Dougados M, Chen YC, Greenwald M, Drescher E, Klar R, Xie L, de la Torre I, Rooney TP, Witt SL, Schlichting DE, de Bono S, Emery P.
RMD Open. 2018 May 8;4(1):e000662. DOI: 10.1136/rmdopen-2018-000662

Once daily baricitinib (BARI) inhibited radiographic progression of structural joint damage in patients with an inadequate response or intolerance to csDMARDs over 48 weeks. Current treatment goals aim to use DMARDs to inhibit structural joint damage and prevent long-term functional disability. In RA-BUILD¹, BARI was shown to significantly reduce radiographic joint damage progression in patients with active RA, with an intolerance or inadequate response to csDMARDs. Here, the authors repor...

Keywords: JAK, Baricitinib, Clinical, Radiographic

Translated by: Toz

Tofacitinib ile Tedavi Edilen Romatoid Artritli Hastalarda Uzun Dönem Radyografik ve Hasta Bildirimli Sonuçlar: ORAL Start ve ORAL Scan Post-hoc Analizler

Strand V, Kavanaugh A, Kivitz AJ, van der Heijde D, Kwok K, Akylbekova E, Soonasra A, Snyder M, Connell C, Bananis E, Smolen JS.
Rheumatol Ther. 2018 Dec;5(2):341-353. doi: 10.1007/s40744-018-0113-7

Tofacitinib (TOF) therapy reduced the progression of structural joint damage at 2 years, in patients of all disease states, compared with patients given methotrexate (MTX). Early intervention with DMARDs aim to prevent the development of future RA symptoms and inhibit the progression of structural damage to the joints. This post-hoc analysis uses data from two Phase 3 TOF studies, to examine the efficacy of early intervention with TOF on long-term radiographic outcomes and disease activity sta...

Keywords: JAK, Tofacitinib, Clinical, Radiographic

Translated by: Toz

March 18

Romatoid Artritli Hastalarda Metotreksat veya Glukokortikoid Başlanmasının yada Kesilmesinin Tofacitinib Etkinliği Üzerine Etkisi: Bir Post Hoc Analiz

Fleischmann R, Wollenhaupt J, Cohen S, Wang L, Fan H, Bandi V, Andrews J, Takiya L, Bananis E, Weinblatt ME.
Rheumatol Ther 2018 Jun; 5(1):203–14. DOI: 10.1007/s40744-018-0093-7

Methotrexate (MTX) or Glucocorticoid (GC) discontinuation has little effect on CDAI response in patients given tofacitinib (TOF) for up to 3 years. Patients receiving TOF who showed initial improvements benefitted from initiation of MTX or GCs. Concomitant treatments such as MTX or GC are commonly used in combination with RA therapies to improve or accelerate clinical responses. However, their use is associated with many adverse events so clinicians aim to use them for a minimal duration. This ...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Translated by: Toz

Daha Önce Biyolojik Kullanan Refrakter Artritli Hastaların Barisitibin Yanıtı

Genovese MC, Kremer JM, Kartman CE, Schlichting DE, Xie L, Carmack T, Pantojas C, Burston JS, Tony HP, Macias WL, Rooney TP, Smolen JS.
Rheumatology (Oxford) 2018 May; 57(5):900-908

Baricitinib (BARI) 2 or 4 mg had a beneficial treatment effect on patients with moderate to severe RA compared with placebo (PBO), irrespective of the number or nature of prior patient bDMARD use. The current therapeutic target for patients with established RA is low disease activity, but many patients fail to achieve this due to inadequate responses to DMARD therapies. With this patient population growing, therapies for these patients are considered one of the greatest unmet needs in RA. This...

Keywords: JAK, Baricitinib, Clinical, Efficacy

Translated by: Toz

February 18

Erken Romatoid Artrit Hastalarında Radyografik Eklem Hasarı: Tocilizumab ve Metotreksat-Bazlı Hedefe Yönelik Tedavi Stratejilerinin Karşılaştırılması

Teitsma X, Jacobs JWG, Welsing PMJ, Pethӧ-Schramm A, Borm MEA, van Laar JM, Lafeber FPJG, Bijlsma JWJ.
Rheumatology (Oxford) 2018; 57(2):309–17

Tocilizumab (TCZ) therapy in DMARD-naïve patients with RA, is more effective at reducing erosion progression, particularly in the feet, compared with treat-to-target methotrexate (MTX) therapy. This analysis looked at radiographic joint damage, including separate examination of erosion progression and joint space narrowing (JSN) in the hands and feet of patients enrolled in the U-Act-Early trial. Radiographic damage is a common symptom of RA, with treat-to-target strategies aimed at pre...

Keywords: IL-6, Tocilizumab, Clinical, Radiographic

Translated by: Bahtiyar Toz

Romatoid Artritli Çinli Hastalarda Tofacitinib ve Konvansiyonel Sentetik Hastalık Modifiye Edici Antiromatizmal İlaçlar: Bir Faz 3 Randomize Kontrollü Çalışmanın Hasta Tarafından Bildirilen Sonuçları

Li Z, An Y, Su H, Li H, Xu J, Zheng Y, Li G, Kwok K, Wang L, Wu Q.
Int J Rheum Dis 2018; 21(2):402–14

This Chinese sub-population of patients with RA from ORAL Sync reported significant improvements in patient-reported outcomes (PROs), which were maintained up to 12 months from tofacitinib (TOF) treatment initiation. ORAL Sync was a randomised, Phase 3 study investigating TOF therapy in combination with csDMARDs in patients with active RA who had previously had an inadequate response to csDMARDs. To date, this is the only Phase 3 study of TOF in patients from China with RA. This analysis inclu...

Keywords: JAK, Tofacitinib, Clinical, PRO

Translated by: Bahtiyar Toz

December 17

Romatoid Artritli Hastalarda Glukokortikoidlerin Tofasitinib'in Klinik ve Radyografik Etkinliği Üzerine Etkisi:6 Faz III Çalışmadan Elde Edilen Verilerin Posthoc Analizi

Charles-Schoeman C, van der Heijde D, Bumester GR, Nash P, Zerbini CAF, Connell CA, Fan H, Kwok K, Bananis E, Fleischmann R.
J Rheumatol 2018 Feb; 45(2):177-87

In this post hoc analysis, six Phase 3 studies were used to analyse the effect of glucocorticoids (GC) on the efficacy of tofacitinib (TOF) in patients with RA. Concomitant use of GC did not affect the clinical or radiographic outcomes of patients treated with TOF. Data from all six clinical trials were evaluated, with four studies (ORAL Scan, ORAL Standard, ORAL Sync and ORAL Step) being pooled for analysis. In these studies, MTX was used as a comparison and patients were required to maintain ...

Keywords: JAK, Tofacitinib, Clinical, Phase 3

Translated by: Bahtiyar Toz

Romatoid Artritde Tofasitinib Tedavisi: Biyolojik-naif ve - Deneyimli Hastaların Doğrudan Karşılaştırmalı Bir Çalışması

Mori S, Yoshitama T, Ueki Y.
Intern Med. 2018 Mar 1;57(5):663-670. doi: 10.2169/internalmedicine.9341-17

This 6-month prospective direct comparison study analysed the effectiveness of tofacitinib (TOF) therapy on bDMARD-naïve and bDMARD-experienced patients. bDMARD-naïve patients were more responsive to TOF therapy than bDMARD-experienced patients. The study analysed the data of 113 patients diagnosed with high or moderate disease activity, defined using CDAI scores. All patients had failed to achieve CDAI low disease activity or remission with MTX therapy for ≥3 months. Patients were...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Translated by: Bahtiyar Toz

August 17

IL-6 Yolağı Inhibitörü Alan Romatoid Artritli Hastalarında 28 Eklemli Hastalık Aktivite Skoru (DAS28) için Yeni Önerilen Remisyon Kesim Noktalarının Değerlendirilmesi

Schoels M, Alasti F, Smolen JS and Aletaha D.
Arthritis Res Ther. 2017 Jul 4;19(1):155. doi: 10.1186/s13075-017-1346-5

DAS28 is not currently included in the joint remission definitions of the ACR and the EULAR because its formula is disproportionately influenced by Acute Phase Response (APR). IL-6 pathway blockers or JAK inhibitors greatly reduce APR, causing patients to be classed as in DAS28 remission despite still having multiple swollen joints. To make DAS28 remission criteria more stringent, the alternative cut-points of <1.9 and <2.2 for CRP and ESR, respectively, have been proposed. This study q...

Keywords: IL-6, Tocilizumab, Clinical, Efficacy

Translated by: Bahtiyar Toz

Tümör Nekroz Faktörü Inhibitörleri Arasında Değişim veya Yeni Etki Mekanizmali Tedaviye Geçişin Tedavide Sürekliliği ve Klinik Sonuçları : ABD'de Tümör Nekroz Faktör İnhibitörü Tedavisi Almış Romatoid Artritli Hastaların Gerçek-Dünya Gözlemsel Çalışması

Wei W, Knapp K, Wang L, Chen C-I, Craig GL, Ferguson K Schwartzman S.
Adv Ther. 2017 Aug;34(8):1936-1952. doi: 10.1007/s12325-017-0578-8

This retrospective, observational study used a real-world US clinical database to demonstrate greater effectiveness of switching to a therapy with an alternative mechanism of action (MOA) vs cycling between TNF inhibitors (TNFis) in patients in which TNFi therapy has failed. Between 1 April 2010 and 31 March 2015, a total of 613 of the observed patients failed a TNFi therapy and then either cycled to another TNFi therapy (54.2%) or switched to a therapy with an alternative MOA (45.8%). The most...

Keywords: JAK, Tofacitinib, Real World, Efficacy

Translated by: Bahtiyar Toz

June 17

Metotreksat-Naif Romatoid Artritli Hastalarında �Biyolojikler veya Tofasitinib: �Sistematik Derleme ve Network Meta-analizi

Singh JA, Hossain A, Tanjong Ghogomu E, Mudano AS, Tanjong Ghogomu E, Suarez-Almazor ME, Buchbinder R, Maxwell LJ, Tugwell P, Wells GA.
Cochrane Database Syst Rev. 2017 May 8;5:CD012657. doi: 10.1002/14651858.CD012657

This Cochrane systemic review and network meta-analysis looked at the benefits and harms of biologics or tofacitinib in patients with RA not previously treated with MTX. Using data from 19 RCTs including 6,485 participants, the review found that biologics (abatacept, adalimumab, etanercept, golimumab, infliximab, rituximab) in combination with MTX improved signs and symptoms of RA (ACR50) and increased the chances of remission (DAS <1.6 or DAS28 <2.6). There was also some evidence of an ...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Bahtiyar Toz

Romatoid Artritli Hastalarında TNF İnhibitörleri Arasında Geçiş ile Yeni Etki Mekanizmasına Sahip DMARD Tedavisine Geçişin Sonuçları

Chastek B, Becker LK, Chen CI, Mahajan P and Curtis JR.
J Med Econ 2017;20:464–73

This retrospective study looked at claims-based datasets to establish whether it is preferable to switch to another TNF inhibitor (TNFi) or to a therapy with a different mechanism of action (MOA) when RA treatment failure occurs with an initial TNFi, due to inadequate response or lack of tolerability. Administrative claims data from a large US database were used to compare treatment patterns, treatment effectiveness (based on fulfillment of six criteria) and costs in in the 12 months after RA p...

Keywords: JAK, Tofacitinib, Real World, Value

Translated by: Bahtiyar Toz

May 17

Romatoid Artritli Hastalarda Tofasitinib'in Düşük Hastalık Aktivitesi Sağlandıktan Sonra Kesilmesi: Çok Merkezli, Gözlemsel Çalışma

Kubo S, Yamaoka K, Amano K, Nagano S, Tohma S, Suematsu E, Nagasawa H, Iwata K and Tanaka Y.
Rheumatology. Doi 10.1093/rheumatology/kex068

This study showed that in patients who achieved low disease activity (LDA), it is possible to discontinue tofacitinib without flare in approximately one-third of patients. Patients from the tofacitinib Phase 3 programme and long-term extension study were enroled. Discontinuation was based on physician-patient decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib free at post-treatment Week 52. Of 64 patients treated with tofacitin...

Keywords: JAK, Tofacitinib

Translated by: Bahtiyar Toz

Metotreksat-Naif Erken Romatoid Artritli Hastalarda Metotreksat Monoterapisi veya Tocilizumab Kombinasyonu veya Monoterapisi: Randomize, Plasebo Kontrollü FUNCTION Çalışmasından 2 Yıllık Klinik ve Radyografik Sonuçlar

Burmester GR, Rigby WF, van Vollenhoven RF, Kay J, Rubbert-Roth A, Blanco R, Kadva A and Dimonaco S.
Ann Rheum Dis Published Online First: 7 April 2017. Doi 10.1136/annrheumdis-20160210561

Burmester et al. present data showing that 52-week efficacy and safety of intravenous tocilizumab plus methotrexate, or tocilizumab monotherapy are maintained through to Week 104 in patients with early rheumatoid arthritis. Patients were assigned to four treatment groups: 4 mg/kg TCZ + MTX, 8 mg/kg TCZ + MTX, 8 mg/kg TCZ + placebo or placebo + MTX. Patients not achieving DAS28 ≤3.2 at Week 52 and who were not receiving 8 mg/kg TCZ were rescued to 8 mg/kg TCZ + MTX. Of the 1162 randomly assi...

Keywords: IL-6, Tocilizumab, Clinical, Phase 3

Translated by: Bahtiyar Toz

January 17

Metotreksat ve Biyolojik Naif veya 6 ay Metotreksat Tedavisi Almayan Romatoid Artritli Hastalarında Tocilizumab Monoterapisinin 5 Yıllık Etkinliği ve Güvenliği: AMBITION Çalışması

Jones G, Wallace T, McIntosh MJ, Brockwell L, Gómez-Reino JJ, Sebba A.
J Rheumatol 2017;44:2. DOI 10.3899/jrheum.160287.

Results from the AMBITION study (Actemra versus Methotrexate double-Blind Investigate Trial In mONotherapy), showed the continuing efficacy and safety of tocilizumab up to 264 weeks. AMBITION was a 24-week randomised controlled trial in patients with active RA who were either MTX-naïve or MTX-free for 6 months prior to study entry. Patients received TCZ 8 mg/kg IV Q4W or oral MTX weekly (7.5 mg dose escalating to 20 mg). For those patients who then entered the long-term extension (LTE) stu...

Keywords: IL-6, Tocilizumab, Clinical, Efficacy

Translated by: Bahtiyar Toz

March 16

Romatoid Artrit tanılı yaşlı hastalarda biyolojik tedavilerin kardiyovasküler risk üzerindeki etkileri

Zhang et al.
Ann Rheum Dis 2016;0:1–6 doi:10.1136/ annrheumdis-2015-207870 [Epub ahead of print]

Since RA patients are at an increased risk of a CV event, there have been several studies to determine if RA treatments alter this risk. In a retrospective study, Zhang and colleagues assess the risk of CV events in patients initiating bDMARDs. Using Medicare medical and pharmacy claims data, the incidence rate (IR) of acute myocardial infarction (AMI) and of a composite CHD* was calculated across RA patients initiating 8 different biologics: ABA, ADA, CER, ETA, GOL, INF, RIT, and TOC. There we...

Keywords: IL-6, Tocilizumab, Real World, Cardiovascular

Metotreksata yetersiz yanıtlı romatoid artritli hastalarında metotreksata tosilizumab eklenmesi yada tosilizumab tedavisine geçiş tedavilerinin karşılaştırılması: �52 haftalık prospektif, randomize kontrollü çalışma (SURPRISE çalışması)

Kaneko et al.
Ann Rheum Dis 2016 Jan 5 DOI: 10.1136/annrheumdis-2015-208426 [Epub ahead of print

MTX is the primary drug in RA management because of its long-term effectiveness and safety profile; however, in patients who have insufficient response (IR) to MTX, treatment adjustments are needed – either to combine a bDMARD with MTX or to switch to a bDMARD from MTX. In the SURPRISE study, the efficacy and safety of adding TCZ to MTX (ADD-ON) or switching MTX to TCZ (SWITCH) was evaluated in 233 patients with moderate to highly active RA who were randomised 1:1. Both treatment groups we...

Keywords: IL-6, Tocilizumab, Clinical, Phase 3

Translated by: Bahtiyar Toz

December 15

Romatoid artritli hastalarda tocilizumab ya da adalimumab ile tedaviden sonra lipid ve lipid ile ilişkili kardovasküler risk belirteçlerindeki değişimin karşılaştırılması

Gabay C, McInnes IB, Kavanaugh A, Tuckwell K, Klearman M, Pulley J, Sattar N.
Ann Rheum Dis. 2015;0:1-7. doi:10.1136/annrheumdis-2015-207872 [Epub ahead of print]

RA patients have increased risk of CVD compared with the general population that is not fully explained by traditional risk factors. This is a post-hoc analysis of data from a clinical trial that compared IL-6 and TNF-α signaling inhibition to compare changes in lipids and lipid-associated CV risk markers in 324 patients treated with TCZ IV q4w or ADA SC q2w for 24 weeks. HDL-SAA and sPLA2 IIA is also measured in an additional subpopulation of 87 and 97 TCZ and ADA patients, respectively. ...

Keywords: IL-6, Tocilizumab, Cardiovascular

Translated by: Şafak Mirioğlu

Aktif romatoid artritli ve DMARDlara yetersiz yanıtlı hastaların dahil edildiği bir randomize, faz 3 çalışmada tofacitinib monoterapisinin hastalar tarafından bildirilen sonuçlar üzerindeki etkileri

Strand V, Kremer J, Wallenstein G, Kanik KS, Connell C, Gruben D, Zwillich SH, Fleischmann R.
Arthritis Research & Therapy (2015) 17:307 DOI: 10.1186/s13075-015-0825-9 [Epub ahead of print]

RA presents a significant health and socioeconomic burden particularly in physical functioning, fatigue, and emotional roles. A phase III 6-month study of tofacitinib in patients with active RA, who had prior inadequate responses to cDMARDs or bDMARDs, uses patient-reported outcomes (PROs) to assess the impact on quality of life. Patients were randomized 4:4:1:1 to receive tofacitinib 5 or 10 mg BID, or placebo for 3 months followed by tofacitinib 5 or 10 mg BID. At month 3, tofacitinib 5 and ...

Keywords: JAK, Tofacitinib, Clinical, Phase 3

Translated by: Şafak Mirioğlu

October 15

Romatoid Artrit tanılı hastalarda Tocilizumab ve Abatacept tedavi etkinliğinin eşleştirilmiş eğilim skoru ile karşılaştırılması

Kubo S, Nakayamada S, Nakano K, Hirata S, Fukuyo S, Miyagawa I, Hanami K, Saito K, Tanaka Y.
Annals of the Rheumatic Diseases. 2015 Aug 5. doi:pii: annrheumdis-2015-207784. 10.1136/annrheumdis-2015-207784. [Epub ahead of print]

This study compared the clinical outcomes at one year after the treatment either abatacept or tocilizumab in routine clinical practice. This study employed propensity score matching and demonstrated that abatacept and tocilizumab had comparable continuing efficacies, and that treatment with the drugs resulted in comparable clinical and functional remission rates. Additionally, abatacept and tocilizumab showed similar effectiveness with or without MTX. While clinical efficacies, including SDAI,...

Keywords: IL-6, Tocilizumab, Clinical, Efficacy

Translated by: Bahtiyar Toz

September 15

Metotreksata yetersiz cevap veren, orta-ağır romatoid artritli hastalarda subkutan clazakizumabın etkinliği ve güvenliği: Faz IIb, randomize, çift kör, plasebo/aktif kontrollü, doz aralıklı, çok uluslu bir çalışmanın sonuçları

Weinblatt ME, Mease P, Mysler E, Takeuchi T, Drescher E, Berman A, Xing J, Zilberstein M, Banerjee S, Emery P.
Arthritis & Rheumatology. 2015 Jul 2. doi: 10.1002/art.39249. [Epub ahead of print]

The humanised monoclonal antibody, Clazakizumab (CLZ), binds to circulating interleukin-6 (IL-6) cytokine rather than the IL-6 receptor, blocking both classical and trans-signalling. The purpose of this phase 2B study was to evaluate the efficacy and safety of clazakizumab in patients with inadequate response to methotrexate (MTX). Data on selected response rates – ACR20/50/70, DAS28-CRP, SDAI ≤3.3, CDAI ≤2.8 and the ACR/EULAR Boolean definition – and adverse events were collec...

Keywords: IL-6, Clazakizumab, Clinical, Phase 2

Translated by: Şafak Mirioğlu

July 15

Tocilizumabın uzun dönemdeki güvenliği: Pazarlama sonrası izlemde Japonya’daki 5573 romatoid artritli hastanın 3 yıllık takibinden elde edilen sonuçlar

Kazuhiko Yamamoto, Hajime Goto, Kenzo Hirao, Atsuo Nakajima, Hideki Origasa, Kunihiko Tanaka, Minako Tomobe and Kyoichi Totsuka.
The Journal of Rheumatology. 1 June 2015 DOI: 10.3899/jrheum.141210 [Epub ahead of print]

The humanised anti-interleukin 6 receptor monoclonal antibody tocilizumab (TCZ) has been available in clinical practice for several years. The purpose of this study was to evaluate the long-term safety of for the treatment of RA in a real-world clinical setting as a long-term extension of a single-arm, observational post marketing surveillance study. Data on selected adverse events (AEs) - fatal events, serious infection, malignancy, GI perforation, and serious cardiac dysfunction - were collect...

Keywords: IL-6, Tocilizumab, Clinical, Safety

Translated by: Şafak Mirioğlu

May 15

Artritli hastalarda IL-17A ve TNF-α’ nın izole sinovyositin osteoblastik farklılaşması ve kemik eksplant üzerindeki farklı etkisi

Osta B, Roux JP, Lavocat F, Pierre M, Ndongo-Thiam N, Boivin G, Miossec P.
Frontiers in Immunology. 2015;6:151. doi:10.3389/fimmu.2015.00151

Inflammatory joint diseases such as RA and OA are characterised by bone and consequent joint destruction. The role of fibroblast-like synoviocytes (FLS) in the pathogenesis of such diseases is already established. This study compared the effects of TNF-α and IL-17A on osteogenic differentiation of isolated FLS and on whole bone explants from 3 RA and 10 OA patients. Results showed that isolated RA-FLS appeared more sensitive to the effects of TNF-α and IL-17A compared to OA-FLS. The...

Keywords: Cytokine Signalling, Preclinical

Translated by: Bahtiyar Toz

Aktif Romatoid Artrit hastalarında tofacitinibin ölçülmüş glomerüler filtrasyon oranına etkisinin değerlendirilmesi: Randomiza kontrollü çalışmalardan sonuçlar

Kremer JM, Kivitz AJ, Simon-Campos JA, Nasonov EL, Tony HP, Lee SK, Vlahos B, Hammond C, Bukowski J, Li H, Schulman SL, Raber S, Zuckerman A, Isaacs JD.
Arthritis Res Ther. 2015 Apr 6;17(1):95.

Mean increases from baseline in patient serum creatinine (SCr) levels have been observed in the clinical development programme for the JAK inhibitor tofacitinib. These increases predominantly occurred within the first three months, and reversed with tofacitinib withdrawal. This phase 1, randomised, placebo-controlled, parallel-group, 2-period study assessed changes in measured glomerular filtration rate (mGFR) with tofacitinib, relative to placebo, in 148 patients with active RA. Results sh...

Keywords: JAK, Tofacitinib, Preclinical, MOA

Translated by: Bahtiyar Toz

April 15

Aktif Romatoid Artritli ve Metoktreksata Yetersiz Yanıtlı Hastalarda Sarilumab artı Metotreksat: Bir Faz III Çalışmanın Sonuçları

Genovese MC, Fleischmann R, Kivitz A et al.
Arthritis Rheumatol. Vol. 67, No. 6, June 2015, pp 1424–1437

Biologic DMARDs targeting TNF-alpha, IL-1, T-cell co-stimulatory blockade, B-cell depletion, and IL-6R, as well as the newer JAK inhibitors have greatly improved clinical outcomes in RA. However, not all patients respond to current biologic or small molecule DMARDs. Sarilumab is a fully human anti-IL-6Rα mAb that binds membrane-bound and soluble human IL-6R with high affinity, blocking cis and trans IL-6-mediated signalling. This study (MOBILITY) is the first randomised, double-blind,...

Keywords: IL-6, Sarilumab, Clinical, Phase 3

Translated by: Ege Sinan TORUN

March 15

Aktif Romatoid Artritli Hastalarda Monoterapi Olarak Oral Selektif Bir JAK-3 İnhibitörü Olan Decernotinib’in Randomize, Çift-Kör, Plasebo-Kontrollü, On İki-Haftalık Bir Doz-Aralığı Çalışması

Fleischmann RM, Damjanov NS, Kivitz AJ, et al.
Arthritis Rheumatol. 2015;67(2):334–343.

Decernotinib (VX-509; Vertex Pharmaceuticals Incorporated) is a JAK 3 inhibitor currently under investigation for its potential use in the treatment of RA. The potency and selectivity profiles of this oral compound have already been established in previous trials, so this study aimed to establish the efficacy and safety profiles of the drug, in RA patients who have had an inadequate response to at least one DMARD. Four doses; 25 mg, 50 mg, 100 mg and 150 mg, were evaluated in this placebo-contr...

Keywords: JAK, Decernotinib, Clinical, Phase 2

Translated by: Ege Sinan TORUN

January 15

Romatoid Artritli Hastalarda Sağlıklı Gönüllülere Göre Anormal Lipid Profiline Neden Olan Potansiyel Mekanizmalar ve Bunların Tofacitinib Tarafından Tersine Çevrilmesi

Charles-Schoeman C, Fleischmann R, Davignon J, Schwartz H, Turner S, Beysen C, Milad M, Hellerstein M, Luo Z, Kaplan I, Riese R, Zuckerman A, McInnes IB.
Arthritis Rheumatol. 2015;67(3):616-25.

Active RA is associated with changes in both high- and low-density lipoprotein cholesterol as well as changes in the level and function of several HDL-associated proteins, yet the pathways and mechanisms involved with systemic inflammation altered lipid metabolism have not been determined. In addition, treatments for active RA are known to modify lipid metabolism, such as increasing circulating cholesterol levels. In the clinical development programme, a proportion of tofacitinib-treated patien...

Keywords: Cytokine Signalling, Preclinical, MOA

Translated by: Ege Sinan TORUN

December 14

Metotreksata yetersiz yanıt veren romatoid artritli hastalarda baricitinibin 24 haftadaki güvenlik ve etkinliği

Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, Lee CH, Fidelus-Gort RK, Luchi ME, Rooney TP, Macias WL, Genovese MC.
Ann Rheum Dis. 2015;74(2):333–340

Recent innovations in the treatment of RA have focused on the use of small molecules to inhibit intracellular kinases such as the JAK family. Baricitinib (LY3009104, formerly INCB028050) is an orally administered, potent, selective and reversible inhibitor of JAK1 and JAK2, which has shown anti-inflammatory effects, as well as preservation of cartilage and bone, in preclinical rodent studies. This phase IIb study was designed to investigate multiple doses and dosing regimens of baricitinib, fo...

Keywords: JAK, Baricitinib, Clinical, Phase 2

Translated by: Ege Sinan TORUN

Randomize klinik çalışmalarda biyolojik ilaçlar ve tofacitinib ile tedavi edilen kronik inflamatuar artritli hastalardaki lipid profili değişiklikleri: Bir sistematik derleme ve meta analiz

Souto A, Salgado E, Maneiro JR, Mera A, Carmona L, Gómez-Reino JJ.
Arthritis Rheumatol. 2015;67(1):117–127

Systemic inflammation, reflected by high levels of C-reactive protein and the erythrocyte sedimentation rate, has been identified as an independent risk factor for cardiovascular disease, the most important cause of death in RA and SpA. Studies with TNF antagonists have given contradictory results on cardiovascular risk. As such, this systemic literature search aimed to analyse lipid changes in RA and SpA subjects treated with biologics or tofacitinib in randomized clinical trials. The search ...

Keywords: Cytokine Signalling, Cardiovascular

Translated by: Ege Sinan TORUN

October 14

Aktif romatoid artritli hastaların üçüncü-sıra tedavisinde metotreksat ile birlikte tofacitinib: Bir Faz 3 çalışmadan hastaların-bildirdiği sonuçlar

Strand V, Burmester GR, Zerbini CA, Mebus CA, Zwillich SH, Gruben D, Wallenstein GV.
Arthritis Care Res (Hoboken). 2014 Sep 3. doi: 10.1002/acr.22453. [Epub ahead of print]

For many patients with rheumatoid arthritis, improvements in pain, physical function, fatigue, and health-related quality of life (HRQoL) are more important and meaningful than improvements in joint swelling, tenderness, or inhibition of structural damage. These patient-perceived benefits of RA therapy contribute importantly to overall clinical efficacy. This paper presents patient-reported outcomes (PROs) form the ORAL Step trail, which assessed tofacitinib 5 mg or 10 mg twice daily, or pla...

Keywords: JAK, Tofacitinib, Clinical, PRO

Translated by: Ege Sinan TORUN

August 14

Tofacitinib ile tedavi edilen aktif romatoid artritli hastalarda serum kreatinin düzeylerinde değişiklikler: klinik çalışmalardan elde edilen sonuçlar

Isaacs JD, Zuckerman A, Krishnaswami S, et al.
Arthritis Res Ther. 2014;16(4):R158

Despite preclinical and healthy volunteer studies of tofacitinib showing no evidence of nephrotoxicity, increases in mean serum creatinine levels have been observed in patients treated with the drug during the RA clinical development programme. This report explores the clinical significance of this change. Serum creatinine values and renal adverse event data were pooled from patients who received =1 dose of tofacitinib either with background DMARDs or as monotherapy in five Phase 3 studies a...

Keywords: JAK, Tofacitinib, Preclinical, MOA

Translated by: Ege Sinan TORUN

Romatoid Artritli Hastalarda Tofacitinib’in Faz II, III ve Uzun-Dönem Uzatma Çalışmalarında Enfeksiyonun ve Tüm-Nedenlere-Bağlı Mortalitenin Analizi

Cohen S, Radominski SC, Gomez-Reino JJ, et al.
Arthritis Rheumatol. 2014;66(11):2924–2937

This study pools data from the global tofacitinib RA development programme (phase II, phase III and long-term extension studies) to determine the rate of infections and all-cause mortality with tofacitinib treatment. In total, 4,789 patients within these studies received tofacitinib, at varying doses and with varying duration. The overall incidence rate of serious infections was 3.09 events/100 patient-years (95% CI 2.73–3.49), which was stable over time, with pneumonia and skin and s...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Ege Sinan TORUN