WCIM 2014 SEOUL KOREA 225
Poster Session
The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
PS 0690 Rheumatology
Freedom Struggle Against Rheumatoid Arthritis
Kedar BHIDE1 Indira Hospital, India1
Background: Evidence from 4500 BC native Americans at Tennessee, 1500 BC Papy- rus from Egypt to the fi rst description of arthritis 400 BC from Hippocrates, Galen and many others, on the way from Paracelsus, Ayurveda, Sydenham, Beauvais to Benjamin Brodies 1818s description, Dr. Garrod in 1859 named the disease` Rheumatoid Arthritis’
and the struggle began offi cially. 1896s illustrated descriptions of Bannatyne, forma- tion of ‘International Committee of Rheumatism’, Camroe coining the term ‘Rheuma- tologist’ in 1940 & Hollander in 1949 ‘Rheumatology’, the struggle got its momentum with discovery of` Rheumatoid factor’ by Dr. Waller in 1940. On the treatment front use of Willio plant extract by Hippocrates & Galen to Grehardt & Hoffman’s (1832,1897) discovery of acetyl salicylic acid opened the gates of NSAIDS, John Vane in 1971 hon- ored with Nobel Prize for his elucidation of action of NSAIDS, with addition of COX2 selective inhibitors by Simmons in 1991. Kendal, Hench and Reichstein Nobely honored for pioneering discovery and application of corticosteroids. Accidental discovery of Gold and Antimalarials as early DMARDs [disease modifying anti rheumatoid drugs]
got the struggle augmented with DR. Y. Subbarao’s development of Methotrexate and now a new breed of biological agents promise a greater freedom from pain and suf- fering of Rheumatoid Arthritis.
Methods: The literature was reviewed from 100s of sites on internet with intricate details and various text books and Journals, systematically and methodically arranging events in chronological order of discover.
Results: There is astonishing wealth of information and inspiration is achieved, which we never realize while studying in Medical College or in Practice and we really under- stand the worth of it.
Conclusions: As per William Osler`` …the knowledge which is your privilege today to acquire so early has cost others. We are all of us, debtors to our profession.’’
PS 0691 Rheumatology
A Randomized, Double-Blind, Phase 3 Equivalence Trial Comparing the Etanercept Biosimilar, Hd203, to Ref- erence Etanercept, in Combination with Methotrexate (MTX) in Korean Patients with Rheumatoid Arthritis (RA)
Sang-Cheol BAE1, Jinseok KIM2, Jung-Yoon CHOE3, Won PARK4, So-Ra LEE5, Yong-Ho AHN6 Hanyang University Seoul Hospital, Korea1, Jeju National University Hospital, Korea2, Catholic University of Daegu, Korea3, Inha University Hospital, Korea4, Clinical Development/Regulatory Affairs, Hanwha Chemical Biologics, Korea5, R&D Center, Hanwha Chemical Biologics, Korea6
Background: Etanercept is a recombinant fusion protein that blocks TNF. HD203 is a biosimilar of etanercept with demonstrated comparability across pharmacokinetics, safety and tolerability. The objectives of this study were to evaluate equivalence in effi cacy and compare safety of HD203 with reference etanercept, in combination with MTX in patients with RA. (ClinicalTrials.gov NCT01270997).
Methods: Korean patients (male or female aged =20 years) with active RA were ran- domized (1:1) to 25 mg HD203 or reference etanercept, administered subcutaneously twice weekly with MTX for 48 weeks. The primary endpoint was the proportion of pa- tients achieving ACR20 at week 24. Secondary endpoints included ACRn, DAS28, and EULAR response at week 24 and 48, safety and immunogenicity.
Results: In total, 294 patients were randomized: HD203, n=147; reference etanercept, n=147. The proportion of patients achieving ACR20 at week 24 was not signifi cantly different between HD203 and reference etanercept. Equivalent effi cacy was demon- strated within predefined margins. There were no significant differences between proportions achieving ACR20 at week 12 and 48. ACR50 and ACR70 displayed similar trends. There were no signifi cant differences between groups for ACRn, DAS28, and EULAR response. Safety set analysis (HD203, n=147; reference etanercept, n=146) re- vealed no signifi cant difference for treatment-emergent (all-causality) adverse events (AEs): HD203 76.87% vs. reference etanercept 78.08% (p=0.8040). No significant differences between HD203 and reference etanercept were observed for adverse drug reactions, serious AEs, or discontinuations due to AEs. Few patients tested positive for anti-drug antibodies.
Conclusions: The study met the primary endpoint of demonstrating equivalent effi cacy of HD203 compared to reference etanercept. HD203 was well tolerated, with a safety profi le comparable to reference etanercept in this population of patients with RA.
PS 0692 Rheumatology
Anti TNF-Alpha Therapy in Rheumatoid Arthritis Pa- tients Disease Activation with, Correlation Between Serum Level of ESR and CRP Levels
Gulcin GUNGOR OLCUM1, Guven KOC1, Fidan Canan CELIK YAGAN3, Ece YIGIT TASKIN1, Senem ERTILAV1, Hanife Serife AKTAS1, Sati Sena YILDIZ1, Demet ATAMAN TASAN4, Fatih AKDOGAN1, Sema BASAT1, Mehmet Ali USTAOGLU2
Umraniye Training and Research Hospital, Turkey1, Dr.Lutfi Kirdar Kartal Trainig and Research Hospital, Turkey2, Zeynep Kamil Womens and Children Training and Research Hospital, Turkey3, Medical Park Hospital, Turkey4
Background: RA is a chronic systemic disease manifest with multiple joint infl am- mation. Vasculitis, heart, lung disease, extra-articular symptoms can also be present.
TNF-a,IL-6 and mediators such as cytokines, have been shown to have an important role in this infl ammatory process.Anti-TNF drugs considered to be effective in pre- venting;RA,disability and joint destruction. CRP is one of the best indicators of infl am- mation though, ESR is an indirect indicator of infl ammation and ESR levels affected by age, sex, status and anemia. ESR and CRP levels in patients with RA, disease activity and has been shown to correlate with radiographic fi ndings In this study, we aim to to show the correlation between ESR, CRP levels with disease activity in patients receiv- ing anti-TNF alpha therapy.
Methods: In this Retrospective study between January 2006 to March 2010 patients diagnosed with RA were evaluated in two groups. In the study group patients re- ceiving at least one year of TNF-alpha were included where as in the control group patients only receiving DMARD were include. Only female patients were involved in both groups. There were 46 women in the study and 47 women in the control group.
Disease severity and DAS 28 score was used to determine the disease activity. For statistical analysis Number Cruncher Statistical System 2007 & PASS 2008 Statistical Software (Utah,USA) was used.
Results: In patients receiving anti-TNF alpha therapy DAS 28 scores showed statisti- cally signifi cant correlation with the ESR. A statistically signifi cance between DAS 28 and CRP were not found. In control group with only DMARD treatment, the DAS 28
226 32nd World Congress of Internal Medicine (October 24-28, 2014) WCIM 2014
showed no signifi cant correlation between ESR nor CRP.
Conclusions: According to these results, in long-term follow-up; RA patients receiving, anti-TNF in signifi cant correlation with ESR showed better disease activity.
PS 0693 Rheumatology
Safety of TNF Inhibitor Therapy in Patients Who Have Had a Prior Malignancy
Seung-Hyeon BAE1, Su Min AHN1, Do Ho YIM1, Seokchan HONG1, Yong-Gil KIM1, Chang-Keun LEE1, Bin YOO1
Asan Medical Center, Korea1
Background: According to the 2012 American College of Rheumatology Recommen- dations, it is possible to start biologic agent in patients who have been treated for sol- id tumor. But, there is no evidence in patients with history of a solid cancer treatment within the past 5 years. The purpose of this study was to explore the infl uence of TNF inhibitor (TNFi) therapy in this subgroup patients.
Methods: The medical records of all patients (n=859) that received TNFi therapy at a single rheumatology clinic between June 2005 and May 2014 were retrospectively re- viewed. Among them, data from patients who had a history of solid cancer treatment before TNFi therapy were collected and patient outcomes were evaluated especially for those who have been treated cancer within the last 5 years.
Results: Of 859 patients who underwent TNFi therapy, 22 patients had a history of malignancy before initiating TNFi therapy for ankylosing spondylitis (AS) and rheuma- toid arthritis (RA) (Table 1). The median AS, RA disease duration was 8 (3.75-12.25) years and median time to TNFi therapy after prior cancer treatment was 62.5 (21.25- 140.25) months. Most common site of prior cancer is stomach (36.4%) and followed by thyroid, colorectum, liver, kidney, and breast. There was no recurrence of previous cancer during 40 (7.0-50.75) months of TNFi therapy. Especially, 10 patients started TNFi therapy before 5 years prior cancer treatment (Table 2). All of our 10 cases were limited in an early stage without distant metastasis. When they have been followed for 36 months, recurrence of cancer was not found.
Conclusions: Our results suggest that starting TNFi therapy in patients with history of solid cancer in locally limited stage is safe even less than 5 years after prior cancer treatment.
PS 0694 Rheumatology
Appearance of Psoriasis after TNF-a Blocker and Use of Ustekinumab or Tocilizumab for Refractory Monoar- thritis
Jinyoung MOON1, Dong Jin GO1, Jae Hyun LEE1, Jin Kyun PARK1, Eun Bong LEE1, Yeong Wook SONG1, Jai Il YOUN2, Eun Young LEE1
Seoul National University Hospital, Korea1, National Medical Center, Korea2
Nowadays, tumor necrosis factor-a (TNF-a) blockers are used for the treatment of RA, infl ammatory bowel diseases (IBD), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis. Paradoxically, there are some reports of appearance of psoriasis after TNF-a blockers. We report a patient who have seronegative mono-rheumatoid arthritis (mono-RA) on knee joint that experienced psoriasis after TNF-a blocker ther- apy (adalimumab and etanercept). For the patient, oral medication is not available due to intolerance; thus, we tried ustekinumab which is an anti-IL-12/23 monoclonal antibody that has been used to treat psoriasis. After ustekinumab injection, psoriatic skin lesions and joint symptoms were much improved in the patient. But in the follow- ing period, joint pain and swelling aggravated and synovial fl uid cytokine levels such as IL-6 and IL-17 were elevated. Treatment was changed to tocilizumab, humanized monoclonal antibody against IL-6 receptor. After injection, knee joint swelling rapidly subsided without worsening of psoriatic skin lesion.
PS 0695 Rheumatology
Sarcoid Like Granuloma Developed during Adalimumab Therapy in Ankylosing Spondylitis
Jae-Hoon KIM1, Jae Kyeom SHIM2, Young Ho SEO3, Sung Jae CHOI4, Young Ho LEE5, Jong Dae JI6, Kyung Ho KANG7, Gwan Gyu SONG8
Korea University Guro Hospital, Korea University College of Medicine, Korea1, Korea University Guro Hospital, Korea University College of Medicine, Korea2, Korea University Ansan Hospital, Korea Univer- sity College of Medicine, Korea3, Korea University Ansan Hospital, Korea University College of Medicine, Korea4, Korea University Anam Hospital, Korea University College of Medicine, Korea5, Korea University Anam Hospital, Korea University College of Medicine, Korea6, Korea University Guro Hospital, Korea University College of Medicine, Korea7, Korea University Guro Hospital, Korea University College of Medicine, Korea8
Introduction: Adalimumab is a full human monoclonal antibody that inhibits tumor necrosis factor-alpha (TNF-a). It has recently been shown to be effective in the treat- ment of rheumatoid arthritis, ankylosing spondylitis (AS). As the pulmonary complica- tion of TNF-a antagonist, infection, interstitial pneumonitis, sarcoidosis and pulmonary vasculitis has been reported. Sarcoidosis is a rare complication among them. Here, we report a patient who has developed sarcoid like granuloma confi rmed by lung biopsy following adalimumab therapy for AS.
Case Description: The patient is a 26-year-old man with a history of ankylosing spondylits evolving over the previous 9 years, who had received treatment with non-steroid anti-infl ammatory drugs and sulfasalazin. Adalimumab was injected at a dose of 40 mg twice a month for 9 months with a very positive clinical response. He is admitted due to the patch opacity showed on the right upper and middle lobe at chest radiograph in annual medical checkup. Computed tomography (CT) of the chest revealed various sized multiple nodules on the right upper and middle lobe and lymph node enlargement in both hilum and right paratracheal area. The blood analysis de- termined ESR 19 mm/hr, CRP 2.16 mg/L with normal renal and hepatic function. The levels of the angiotensin-converting enzyme were 95.7 U/L (normal value 9.0~47.0).
The tuberculosis skin test and the interferon gamma releasing assay were negative.
Blood cultures and sputum analysis were negative. The microbiological analysis of
