Celltrion Research Articles

Ustekinumab Biosimilars

Ustekinumab is a fully human IgG1k monoclonal antibody that binds with high affinity and specificity to the p40 subunit of interleukins (IL-) 12 and 23, inhibiting their activity by preventing binding to their receptors. The European extension of the patent (Supplementary Protection Certificate) of ustekinumab expired on 20 July 2024. Biosimilar alternatives to ustekinumab are now an additional option for treating patients. The efficacy data for this drug in moderate-to-severe psoriasis obtained both from clinical trials and indirect comparisons through meta-analyses, are superior to those of etanercept and adalimumab, and its safety profile is more favorable than that of tumor necrosis factor (TNF) inhibitors. Several ustekinumab biosimilars have already been approved by regulatory agencies: between October 2023 and October 2024, Wezlana® (Amgen ABP 654), Uzpruvo® (Alvotech AVT04) and Pyzchiva® (Samsung/Bioepis SB17) have been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). SteQeyma® (Celltrion Healthcare CT-P43) was approved by the EMA in August 2024. Otulfi® (Fresenius Kabi/Formycon) was approved by the FDA in October 2024. Several other potential biosimilar candidates are under development, including BAT2206 (Bio-Thera), DMB-3115 (Dong-A ST), QX001S (Qyuns Therapeutic), BFI-751 (BioFactura), NeuLara (Neuclone), ONS3040 (Oncobiologics), and BOW090 (Epirus Biopharmaceuticals). In most cases, these monoclonal antibodies are expressed in cell lines (e.g., Chinese Hamster Ovary, CHO) different from those used for the originator (Sp2/0 spleen cell murine myeloma); of note, the cell line of origin is not a requirement for biosimilarity in the totality-of-evidence comparison exercise and may facilitate the production and reduce the immunogenicity of biosimilars originated in CHO cultures. This narrative review summarizes the available data on characteristics of the full comparability exercises and comparative clinical trials of these drugs.

Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study

We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of response. Personalised Anti-TNF therapy in Crohn's disease (PANTS) is a UK-wide, multicentre, prospective observational cohort study reporting the rates of effectiveness of infliximab and adalimumab in anti-TNF-naive patients with active luminal Crohn's disease aged 6 years and older. At the end of the first year, sites were invited to enrol participants still receiving study drug into the 2-year PANTS-extension study. We estimated rates of remission across the whole cohort at the end of years 1, 2, and 3 of the study using a modified survival technique with permutation testing. Multivariable regression and survival analyses were used to identify factors associated with loss of response in patients who had initially responded to anti-TNF therapy and with immunogenicity. Loss of response was defined in patients who initially responded to anti-TNF therapy at the end of induction and who subsequently developed symptomatic activity that warranted an escalation of steroid, immunomodulatory, or anti-TNF therapy, resectional surgery, or exit from study due to treatment failure. This study was registered with ClinicalTrials.gov, NCT03088449, and is now complete. Between March 19, 2014, and Sept 21, 2017, 389 (41%) of 955 patients treated with infliximab and 209 (32%) of 655 treated with adalimumab in the PANTS study entered the PANTS-extension study (median age 32·5 years [IQR 22·1-46·8], 307 [51%] of 598 were female, and 291 [49%] were male). The estimated proportion of patients in remission at the end of years 1, 2, and 3 were, for infliximab 40·2% (95% CI 36·7-43·7), 34·4% (29·9-39·0), and 34·7% (29·8-39·5), and for adalimumab 35·9% (95% CI 31·2-40·5), 32·9% (26·8-39·2), and 28·9% (21·9-36·3), respectively. Optimal drug concentrations at week 14 to predict remission at any later timepoints were 6·1-10·0 mg/L for infliximab and 10·1-12·0 mg/L for adalimumab. After excluding patients who had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3 were, for infliximab 34·4% (95% CI 30·4-38·2), 54·5% (49·4-59·0), and 60·0% (54·1-65·2), and for adalimumab 32·1% (26·7-37·1), 47·2% (40·2-53·4), and 68·4% (50·9-79·7), respectively. In multivariable analysis, loss of response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug concentrations at week 14 (infliximab: hazard ratio [HR] for each ten-fold increase in drug concentration 0·45 [95% CI 0·30-0·67], adalimumab: 0·39 [0·22-0·70]). For patients treated with infliximab, loss of response was also associated with female sex (vs male sex; HR 1·47 [95% CI 1·11-1·95]), obesity (vs not obese 1·62 [1·08-2·42]), baseline white cell count (1·06 [1·02-1·11) per 1 × 109 increase in cells per L), and thiopurine dose quartile. Among patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response (HR 1·95 [95% CI 1·17-3·25]). By the end of year 3, the estimated proportion of patients who developed anti-drug antibodies associated with undetectable drug concentrations was 44·0% (95% CI 38·1-49·4) among patients treated with infliximab and 20·3% (13·8-26·2) among those treated with adalimumab. The development of anti-drug antibodies associated with undetectable drug concentrations was significantly associated with treatment without concomitant immunomodulator use for both groups (HR for immunomodulator use: infliximab 0·40 [95% CI 0·31-0·52], adalimumab 0·42 [95% CI 0·24-0·75]), and with carriage of HLA-DQA1*05 risk variant for infliximab (HR for carriage of risk variant: infliximab 1·46 [1·13-1·88]) but not for adalimumab (HR 1·60 [0·92-2·77]). Concomitant use of an immunomodulator before or on the day of starting infliximab was associated with increased time without the development of anti-drug antibodies associated with undetectable drug concentrations compared with use of infliximab alone (HR 2·87 [95% CI 2·20-3·74]) or introduction of an immunomodulator after anti-TNF initiation (1·70 [1·11-2·59]). In years 2 and 3, 16 (4%) of 389 patients treated with infliximab and 11 (5%) of 209 treated with adalimumab had adverse events leading to treatment withdrawal. Nine (2%) patients treated with infliximab and two (1%) of those treated with adalimumab had serious infections in years 2 and 3. Only around a third of patients with active luminal Crohn's disease treated with an anti-TNF drug were in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predict loss of response by year 3 of treatment, suggesting higher drug concentrations during the first year of treatment, particularly during induction, might lead to better long-term outcomes. Anti-drug antibodies associated with undetectable drug concentrations of infliximab, but not adalimumab, can be predicted by carriage of HLA-DQA1*05 and mitigated by concomitant immunomodulator use for both drugs. Guts UK, Crohn's and Colitis UK, Cure Crohn's Colitis, AbbVie, Merck Sharp and Dohme, Napp Pharmaceuticals, Pfizer, and Celltrion Healthcare.

The Design of an Intelligent Lightweight Stock Trading System Using Deep Learning Models: Employing Technical Analysis Methods

Individual investors often struggle to predict stock prices due to the limitations imposed by the computational capacities of personal laptop Graphics Processing Units (GPUs) when running intensive deep learning models. This study proposes solving these GPU constraints by integrating deep learning models with technical analysis methods. This integration significantly reduces analysis time and equips individual investors with the ability to identify stocks that may yield potential gains or losses in an efficient manner. Thus, a comprehensive buy and sell algorithm, compatible with average laptop GPU performance, is introduced in this study. This algorithm offers a lightweight analysis method that emphasizes factors identified by technical analysis methods, thereby providing a more accessible and efficient approach for individual investors. To evaluate the efficacy of this approach, we assessed the performance of eight deep learning models: long short-term memory (LSTM), a convolutional neural network (CNN), bidirectional LSTM (BiLSTM), CNN Attention, a bidirectional gated recurrent unit (BiGRU) CNN BiLSTM Attention, BiLSTM Attention CNN, CNN BiLSTM Attention, and CNN Attention BiLSTM. These models were used to predict stock prices for Samsung Electronics and Celltrion Healthcare. The CNN Attention BiLSTM model displayed superior performance among these models, with the lowest validation mean absolute error value. In addition, an experiment was conducted using WandB Sweep to determine the optimal hyperparameters for four individual hybrid models. These optimal parameters were then implemented in each model to validate their back-testing rate of return. The CNN Attention BiLSTM hybrid model emerged as the highest-performing model, achieving an approximate rate of return of 5 percent. Overall, this study offers valuable insights into the performance of various deep learning and hybrid models in predicting stock prices. These findings can assist individual investors in selecting appropriate models that align with their investment strategies, thereby increasing their likelihood of success in the stock market.

AFM13 IN PATIENTS WITH CD30 POSITIVE RELAPSED OR REFRACTORY (R/R) PERIPHERAL T CELL LYMPHOMA (PTCL): RESULTS FROM THE PHASE 2 REDIRECT STUDY

Introduction: PTCLs are aggressive hematologic malignancies often with poor prognoses; there is no standard of care therapy for patients with R/R PTCL. AFM13, a tetravalent, bispecific innate cell engager, binds CD30 when expressed on PTCL cells, and CD16A on innate effector cells, augmenting the innate immune response to CD30+ tumor cells. Phase 1 clinical trials of AFM13 in patients with R/R Hodgkin lymphoma (HL) and cutaneous CD30+lymphomas showed a tolerable safety profile and clinical activity; correlative science data in a small group of AFM13-responsive patients with HL showed increased natural killer (NK) cell activity. Methods: A Phase 2 study (NCT04101331) assessed the efficacy of AFM13 in patients with select R/R PTCL subtypes, exhibiting histologically confirmed CD30+expression in ≥1% tumor cells, who had received ≥1 prior systemic therapy. The primary endpoint was to assess the overall response rate (ORR) by FDG-PET per independent review committee. Secondary endpoints included safety, complete response rate (CRR), and duration of response (DoR). Progression-free survival (PFS) and overall survival (OS) were exploratory endpoints. Patients received 200 mg AFM13 intravenously once weekly until disease progression, intolerable toxicity, consent withdrawal or termination by the investigator. Results: Patients (n = 108; age 21–93; 61% male) received AFM13 with a median (min, max) number of infusions of 9.0 (1, 116). PTCL subtypes assessed (n) were: PTCL not-otherwise-specified (PTCL-NOS, 41); angioimmunoblastic T cell lymphoma (AITL, 30); anaplastic large cell lymphoma (ALCL, 26); other (11). Patients had received a mean of 2.7 prior treatment lines; 46.3% received prior brentuximab vedotin (BV), 17.6% received prior auto-transplant. The ORR was 32.4% (CRR was 10.2%); ORR per subtype was 22.0% (PTCL-NOS), 53.3% (AITL), 23.1% (ALCL), and 36.4% (other). Median DoR, PFS, and OS were 2.3 months, 3.5 months, and 13.8 months, respectively. AFM13-related treatment emergent adverse events (TEAEs) occurred in 79/108 patients (73.1%); 14 events in 9 patients (8.0%) were considered serious. The most frequent TEAE was infusion-related reactions, as reported by the investigator, seen in 34/108 patients (31.5%), including 12 Grade 3 events in 6 patients (5.7%). Neutropenia was the most frequent Grade ≥3 TEAE occurring in 9.3% of patients. Conclusion: AFM13 monotherapy demonstrated robust clinical activity in heavily pretreated patients with R/R PTCL. The safety profile of AFM13 was well managed and consistent with previously reported data from prior and ongoing clinical studies with AFM13. These data support future evaluation of AFM13 in combination with other immunotherapies, including allogeneic NK cells, to further potentiate anti-tumor immune responses to CD30+ lymphomas. Keyword: immunotherapy Encore Abstract—previously submitted to AACR 2023 The research was funded by: Affimed GmbH Conflicts of interests pertinent to the abstract W. S. Kim Research funding: Sanofi; BeiGene; Boryung; Roche; Kyowa Kirin Co., Ltd.; Dong-A Pharmaceutical Co., Ltd. J. Shortt Consultant or advisory role: Bristol Myers Squibb; Novartis; Otsuka; Astellis; Mundipharma; Pfizer Research funding: Astex; Amgen; Bristol Myers Squibb; Novartis P. L. Zinzani Consultant or advisory role: MSD; Eusapharma; Novartis; Celltrion Healthcare; Gilead; Janssen-Cilag; Bristol Myers Squibb; Servier; AstraZeneca; Takeda; Roche; Kyowa Kirin; Incyte; BeiGene; Secura Bio; Sandoz; ADC Therapeutics A. Marin-Niebla Other remuneration: Janssen; Gilead-Kite; Roche; Eli Lilly; Takeda; Kiowa-Kirin; AbbVie; AstraZeneca; BeiGene K. Alexis Employment or leadership position: Affimed Inc. Stock ownership: Affimed Inc. M. Emig Employment or leadership position: Affimed GmbH Stock ownership: Affimed GmbH L. Garcia Employment or leadership position: Affimed Inc. Stock ownership: Affimed Inc. A. Overesch Employment or leadership position: Affimed GmbH Stock ownership: Affimed GmbH K. Pietzko Employment or leadership position: Affimed GmbH Stock ownership: Affimed GmbH S. Horwitz Consultant or advisory role: Affimed; Daiichi Sankyo; Kyowa Kirin; ONO Pharmaceuticals; SecuraBio; Takeda; Shoreline Pharmaceuticals; Yingli Pharma; Abcuro Inc. Tublulis GmbH Research funding: ADC Therapeutics; Auxilius Pharma; Celgene; CRISPR Therapeutics; Millennium/Takeda; Seattle Genetics; C4 Therapeutics; Verastem/SecuraBio

Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study

Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p<0·0001), BA.1 (107·3 [86·40-133·2] vs 648·9 [523·5-804·5]; p<0·0001), and BA.4/5 (40·63 [31·99-51·60] vs 223·0 [183·1-271·4]; p<0·0001) variants. Breakthrough infection was significantly more frequent in patients treated with infliximab (119 [13·7%; 95% CI 11·5-16·2] of 871) than in those treated with vedolizumab (29 [7·0% [4·8-10·0] of 417; p=0·00040). Cox proportional hazards models of time to breakthrough infection after the third dose of vaccine showed infliximab treatment to be associated with a higher hazard risk than treatment with vedolizumab (hazard ratio [HR] 1·71 [95% CI 1·08-2·71]; p=0·022). Among participants who had a breakthrough infection, we found that higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and, hence, a longer time to breakthrough infection (HR 0·87 [0·79-0·95]; p=0·0028). Our findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies. Royal Devon University Healthcare NHS Foundation Trust; Hull University Teaching Hospital NHS Trust; NIHR Imperial Biomedical Research Centre; Crohn's and Colitis UK; Guts UK; National Core Studies Immunity Programme, UK Research and Innovation; and unrestricted educational grants from F Hoffmann-La Roche, Biogen, Celltrion Healthcare, Takeda, and Galapagos.

297 (PB077) - CAR T cells in marginal zone lymphoma (MZL) models with acquired resistance to PI3K and BTK inhibitors

Background. MZLs are characterized by an indolent course with median survival over 10 years. However, relapses/progressions are common and if they occur during the during the first 2 years, they heavily impact the median survival. Among the 23 relapsed/refractoryMZL patients treated with the anti-CD19 CAR-T cells axicabtagene ciloleucel (Axi-Cel), the overall response rate was 83% with 73% of complete responses (Jacobson, Lancet Onc 2022; Neelapu, ASH2021). We previously presented MZL-derived models with secondary resistance to BTK/PI3K inhibitors, observing, in some of the resistant cells, an increase in CD19 levels and higher sensitivity to the anti-CD19 loncastuximab tesirine antibody drug conjugate (Arribas, ASH2019, ENA2019, Haematologica 2022). Here, we tested CAR-T cells with costimulatory receptors CD28 or 4-1BB (28z CAR-T and BBz CAR-T), representative of Axi-Cel and tisagenlecleucel (Tisa-Cel), respectively, in these models. Methods: CD19-specific 28z CAR-T and BBz CAR-T produced from 4 healthy donors with retroviral vectors. Transduction efficacy evaluated by protein L staining. MZL models of secondary resistance to PI3K/BTK inhibitors and their parental cells cocultured for 48 h with CAR-T cells (1:1 E: T ratio) after adjusting for transduction efficacy. CAR-T cell-mediated cytotoxicity (CX) calculated as percentage of cell death compared to tumor cells cultured alone. CD19 expression determined by flow cytometry (protein) and RNA-Seq (RNA). Results. We first tested 28z CAR-T and BBz CAR-T against the VL51 cell line and in the 2 derivatives, resistant to various PI3K inhibitors and ibrutinib, respectively. Median CX against parental was 24% and 29% with 28z or BBz CAR-T, respectively. CX was significantly increased against PI3K resistant cells, with a median CX of 62% after coculture with 28z CAR-T and 55% with BBz CAR T cells. Ibrutinib resistant VL51 cells displayed an even higher sensitivity to CAR-T cell killing, with a median CX of 68% after co-culture with 28z CAR-T and 79% with BBz CAR-T cells. Differently from VL51, both parental Karpas1718 and PI3K resistant derivative were equally sensitive to CAR-T cells, with a median 28z CAR-T CX of 72% against parental and 72% against PI3K resistant Karpas1718. Similar results were observed after coculture with BBz CAR-T cells (median CX 67% against parental and 66% against PI3K resistant Karpas1718). The results agreed with CD19 levels, higher in Karpas1718 (parental and derivative) and in the resistant VL-51 derivatives than in parental VL51. Conclusions: Anti-CD19 28z and BBz CAR-T showed maintained or even increased in vitro antitumor activity in MZL models after acquisition of secondary resistance to PI3K/BTK inhibitors. The data support exploring CD19 directed therapeutic modalities for MZL patients. FS, FB: co-senior authors. Work supported by Barletta and Henriette Meyer Foundations. Conflict of interest: Advisory Board: Gilead, AbbVie, Janssen, AstraZeneca, MSD, BMS/ Celgene, Roche, Mei Pharma, Astra Zeneca, Celltrion Healthcare, Incyte, Kite/Gilead. Corporate-sponsored Research: Celgene, Roche, Janssen, Acerta, ADC Therapeutics, Bayer AG, Cellestia, CTI Life Sciences, EMD Serono, Helsinn, ImmunoGen, Menarini Ricerche, NEOMED Therapeutics 1, Nordic Nanovector ASA, Oncology Therapeutic Development, PIQUR Therapeutics AG, Gilead, AbbVie, Janssen.

P009 Biologics prescribing trends over 10 years: a retrospective analysis of 799 patients in routine clinical practice

Abstract Background/Aims To investigate the biologic prescribing trends for a secondary care patient cohort over a 10-year period for rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthropathy (SpA), and compare against current local guidelines. Methods Departmental database holding patient data was interrogated. Labelled data were consolidated into distinct diagnostic categories of rheumatoid arthritis, psoriatic arthritis and spondyloarthropathy. For ease of analysis, biologic drugs were classified based on their mechanism of action into TNF-alpha blockers (TNFi) and non-TNF-alpha blockers (non-TNFi). Data was collated identifying prescribing trends of first, second and third-line therapies for RA, PsA and SpA. This was compared against local NHS guidelines. Overall cost of biologic prescription for first line therapies was calculated Results There were 799 patients with a diagnosis of RA, PsA or SpA. Both RA and PsA had the same general prescribing pattern of TNFi as first-line, another TNFi as second-line and non-TNFi as third-line. In SpA, TNFi were mostly used as first, second and third-line. An adalimumab biosimilar was used first-line in 90 (30.6%) RA patients, 42 (35.1%) PsA patients and 32 (32.3%) SpA patients. Methotrexate was co-prescribed with a TNF-alpha blocker in 128 (58.7%) RA patients, 51 (36.4%) PsA patients and 7 (7.7%) SpA patients. TNFi biosimilar drug prescribing has increased from 33% in 2016 to being the most prescribed drug in 2020 (62%). In the entire database cohort of 926 patients, the vast majority are prescribed biosimilars (Table 1). The overall cost of biologic prescriptions has reduced by 49% from 2019 to 2020 as the proportion of biosimilars prescribed has almost doubled to 69%. Conclusion Biologic prescribing patterns are largely in-keeping with current national and local guidelines. The vast majority of patients are on a biosimilar, which has resulted in significant cost-savings for the department. Disclosure R. Zubairi: None. A. Muhd Adiib Pg Suhaimi: None. L. Olsson: None. R. Smyth: None. D. Baxter: None. A. Laws: None. M.E. Perry: Honoraria; AbbVie, Celltrion Healthcare, Gilead, Lilly, Biogen, Jaansen, Fresenius Kabi.

P081 Quick response codes for digital patient information leaflets in a rheumatology department: a quality improvement project

Abstract Background/Aims Many rheumatology departments provide patients with physical copies of patient information leaflets (PILs). Quick response (QR) codes are a widespread simple means of distributing electronic information, involving delivery of digital information directly to a user subsequent to scanning the code with a smartphone camera. Advantages include reduced paper burden, instant updates and usage monitoring, creating great possibilities for their implementation in healthcare settings. Aim: To design and implement a QR code poster to provide electronic versions of PILs given to rheumatology patients. Methods We met with senior clinicians and nurses to understand limitations of the current paper leaflet system and the desire for a digital alternative. A pilot questionnaire was then offered to patients attending clinics over two weeks to gauge attitudes to QR codes and identify PILs they had most interest in, in line with patient-centred care. Subsequent to a positive response, possible QR code management systems were investigated to select a platform with dynamic QR codes allowing tracking of usage metrics. A poster was designed, with eight QR codes leading to PILs from Versus Arthritis focusing on lifestyle aspects of rheumatic disease, as a reflection of both patient interest and clinician desire. Posters were displayed in clinic waiting areas to allow patients to scan them at their convenience. Clinicians were advised to signpost patients towards the QR codes to maximise use. Smaller copies of the poster were also made available for clinicians to distribute directly to patients at clinics, and appended to patient letters. Results 14 patients completed the pilot questionnaire. Despite clinicians’ regular distribution of paper leaflets, 35.7% reported they had never read a PIL. 42.9% of patients were more likely to read information about their condition on their phone rather than from a paper leaflet. 35.7% would like to scan a QR code to get digital information leaflets on their phone. Patients were almost equally interested in PILS about lifestyle (78.6%) and their diagnosed condition (78.6%) as medications (71.4%). PIL topics patients most commonly expressed an interest in included diet (71.4%), footcare (64.3%), pain (64.3%), fatigue (64.3%), complementary and alternative medicine (57.1%), emotional wellbeing (50%), gadgets and equipment for arthritis (50%) and keeping active (50%). QR codes leading to relevant PILs were thus selected for inclusion on the poster. Conclusion There is a clear demand for digital PILs both from patients and clinicians. This ongoing quality improvement project has been successful in planning, designing and implementing a QR code poster to enhance patient access to information about lifestyle implications of rheumatic disease. Roll out of the posters has been successful and the project now requires monitoring of the uptake and usage pattern to further refine the delivery of digital QR code PILs. Disclosure R. Zubairi: None. A. Muhd Adiib Pg Suhaimi: None. L. Olsson: None. R. Smyth: None. D. Baxter: None. A. Laws: None. M.E. Perry: Honoraria; AbbVie, Celltrion Healthcare, Gilead, Lilly, Biogen, Jaansen, Fresenius Kabi.

INTENSIFIED (INTRAVENOUS AND INTRATHECAL) CNS PROPHYLAXIS IN PRIMARY TESTICULAR DIFFUSE LARGE B‐CELL LYMPHOMA: 5‐YEAR RESULTS OF THE IELSG30 TRIAL

Introduction: Primary diffuse large B-cell lymphoma of the testis (PTL) represents a unique condition characterized by high long-term risk of contralateral testis and central nervous system (CNS) relapse (>30% at 15 years) in historical series (Zucca et al, JCO 2002). Immunochemotherapy associated with intrathecal CNS prophylaxis and contralateral testis radiotherapy (RT) improved patient outcome, with a virtual elimination of contralateral recurrences and significant reduction (6% at 5 years) of CNS relapses in the IELSG10 trial (Vitolo et al., JCO 2011). The International Extranodal Lymphoma Study Group (IELSG), in cooperation with the Italian Lymphoma Foundation (FIL), coordinated the multicenter phase II IELSG30 study to assess activity and feasibility of intensified CNS prophylaxis in combination with chemoimmunotherapy and RT. Patients and Methods: Patients with stage I-II PTL were eligible. Treatment consisted of 6 cycles of the standard R-CHOP21 regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone every 21 days); 4 doses of intrathecal liposomal cytarabine; 2 courses of intravenous (iv) intermediate-dose methotrexate (1.5 gr/m2) and RT (25-30 Gy) to the contralateral testis. The study was designed to demonstrate (80% power, a = .05) a PFS improvement from 67% to 82% at 10 years (primary endpoint). Results: Fifty-four patients (median age: 66 years, range: 37-79 years) with untreated stage I (n = 32) or II (n = 22) PTL were treated with R-CHOP21, 53 received at least 3 doses of intrathecal CNS prophylaxis, 48 received at least one dose of iv methotrexate and 50 received prophylactic RT. No unexpected side effects were observed. At a median follow-up of 5 years, 7 patients progressed and 7 died, with 5-year PFS of 88% (95%CI, 74-94%) and 5-year OS of 92% (95%CI, 79%-97%). No CNS relapses occurred. In 4 cases, both nodal and extranodal relapses were reported, the latter including the gastrointestinal tract and the pleurae in the same patient, as well as, 1 patient each, the kidneys, the spinal canal (extra-axial) and the contralateral testis (9 years after RT). Two patients relapsed only at extranodal sites (skin, adrenal gland), 1 had nodal relapse. Notably, 4 of 7 failures were late relapses occurring after 6 to 10 years from treatment. Causes of death were lymphoma (n = 4), second cancer (n = 1), cerebral vasculopathy (n = 1), unknown (n = 1). The research was funded by: Mundipharma provided the drug depocyte free of charge Keywords: Combination Therapies, Radiation Therapy Conflicts of interests pertinent to the abstract A. J. M. Ferreri Consultant or advisory role: Adienne - Gilead - Novartis - Juno - PletixaPharm Research funding: BMS - Beigene - Pharmacyclics - Hutchison - Medipharma - Amgen - Genmab - ADC - Therapeutics - Gilead - Novartis - Pfizer E. Zucca Consultant or advisory role: Beigene - Celgene - Incyte - Janssen - Merck - Roche - Celltrion Healthcare - Kite (Gilead) Research funding: AstraZeneca - Celgene - Incyte - Janssen - Merck - Roche Educational grants: Roche – Abbvie

Phase 2 Study of Nivolumab Plus Bevacizumab Plus Paclitaxel in Patients with HER2-Negative Metastatic Breast Cancer

Phase 2 Study of Nivolumab Plus Bevacizumab Plus Paclitaxel in Patients with HER2-Negative Metastatic Breast Cancer

Double-Hit Signature with TP53 Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Purpose: We performed detailed genomic analysis on 87 cases of de novo diffuse large B-cell lymphoma of germinal center type (GCB DLBCL) to identify characteristics that are associated with survival in those treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Experimental Design: The cases were extensively characterized by combining the results of immunohistochemistry, cell-of-origin gene expression profiling (Nanostring), double-hit gene expression profiling (DLBCL90), fluorescence in situ hybridization (FISH) cytogenetic analysis for double/triple-hit lymphoma, copy number analysis (CNA), and targeted deep sequencing using a custom mutation panel of 334 genes. Results: We identified four distinct biologic subgroups with different survivals, and with similarities to the genomic classifications from two large retrospective studies of DLBCL. Patients with the double-hit signature but no abnormalities of TP53, and those lacking EZH2 mutation and/or BCL2 translocation, had an excellent prognosis. However, patients with an EZB-like profile had an intermediate prognosis, whereas those with TP53 inactivation combined with the double-hit signature had an extremely poor prognosis. This latter finding was validated using two independent cohorts. Conclusions: We propose a practical schema to utilize genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies.

Consolidation with Nivolumab and Brentuximab Vedotin after Autologous Hematopoietic Cell Transplantation in Patients with High-Risk Hodgkin Lymphoma

Consolidation with Nivolumab and Brentuximab Vedotin after Autologous Hematopoietic Cell Transplantation in Patients with High-Risk Hodgkin Lymphoma

Long-Term Efficacy and Safety (27 months) of the Biosimilar CT-P10 in Patients with Low Tumor Burden Follicular Lymphoma

We assessed long-term safety and efficacy of CT-P10 and rituximab in patients with newly diagnosed low-tumour-burden follicular lymphoma (LTBFL), and following a single transition from rituximab to CT-P10. This double-blind, parallel-group, active-controlled phase 3 trial randomized patients with CD20+ LTBFL to receive CT-P10 or US-sourced rituximab (375 mg/m2 intravenous). Induction therapy (weekly for 4 cycles) was followed by a 2-year maintenance period for patients achieving disease control (CR, CRu, PR and SD). During the maintenance, CT-P10 or rituximab were administered every 8 weeks (6 cycles) in the first year and additional CT-P10 was administered every 8 weeks (6 cycles) in the second year. Secondary endpoints (reported here) were overall response rate during the study period, progression-free survival, time-to-progression, and overall survival. Safety and immunogenicity were also evaluated over the study period. Between Nov 9, 2015 and Jan 4, 2018, 258 patients were randomised (130 CT-P10; 128 rituximab). Over the study period, 115 (88%; CT-P10) and 111 (87%; rituximab) patients achieved overall response. At a median follow-up of 29·2 months (IQR: 26·1-33·7), median progression-free survival, time-to-progression, and overall survival were not estimable. The KM estimates (95% CI) for OS at 36 months were 98% (93-99) and 97% (89-99) in the CT-P10 and rituximab groups, respectively. Corresponding values for PFS were 80% (70-87) and 68% (54-79), while results for TTP were 82% (72-88) and 68% (54-79) in the CT-P10 and rituximab groups, respectively. (Figure A. OS; Figure B. PFS and Figure C. TTP) Over the study period, 114 (88%) and 104 (81%) patients in the CT-P10 and rituximab groups, respectively, experienced at least one treatment-emergent adverse event (TEAE) and 14 (11%) patients in each group experienced TE-serious adverse events (TESAEs). There were no unexpected safety findings observed during the second year of the maintenance period after single transition from rituximab to CT-P10. Figure 1 Disclosures Kwak: Celltrion Healthcare: Membership on an entity's Board of Directors or advisory committees; Xeme Biopharma/Theratest: Other: equity; CJ Healthcare: Consultancy; Sellas Life Sciences Grp: Consultancy; Enzychem Life Sciences: Membership on an entity's Board of Directors or advisory committees; Antigenics: Other: equity; InnoLifes, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pepromene Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Consultancy. Sancho:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Gelgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Menne:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Other: Travel costs, Speakers Bureau; Pfizer: Honoraria, Other: Travel costs, Speakers Bureau; Celgene: Honoraria, Other: Travel grants; Roche: Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Astra Zeneca: Research Funding; Takeda: Honoraria, Speakers Bureau. Jurczak:Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months; Acerta: Research Funding; Bayer: Research Funding; Janssen: Research Funding; MeiPharma: Research Funding; Pharmacyclics: Research Funding; Roche: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding. Trneny:Gilead: Consultancy, Honoraria, Other: Travel Expenses; Janssen: Consultancy, Honoraria, Other: Travel Expenses; Roche: Consultancy, Honoraria, Other: Travel Expenses; MorphoSys: Consultancy, Honoraria; Celgene: Consultancy; Incyte: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Bristol-Myers Squibb Company: Consultancy, Honoraria, Other: Travel Expenses; Amgen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel Expenses. Ogura:Cellgene: Honoraria; Chugai: Honoraria; Denovo Biopharma: Membership on an entity's Board of Directors or advisory committees; MejiSeika Pharma: Membership on an entity's Board of Directors or advisory committees; Mundi Pharma: Membership on an entity's Board of Directors or advisory committees; SymBio: Membership on an entity's Board of Directors or advisory committees; TevaTakeda: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Membership on an entity's Board of Directors or advisory committees. Kim:Pfizer: Research Funding; Donga: Research Funding; Mundipharma: Research Funding; F. Hoffmann-La Roche: Research Funding; Kyowa Kirn: Research Funding; Celltrion: Research Funding; JJ: Research Funding. Lee:Celltrion, Inc.: Current Employment. Kim:Celltrion, Inc.: Current Employment. Ahn:Celltrion, Inc.: Current Employment. Buske:Roche, Janssen, Bayer, MSD: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen, AbbVie, Pfizer, Celltrion: Honoraria, Speakers Bureau. OffLabel Disclosure: Rituximab monotherapy to LTBFL patients

A Novel Therapeutic DNA Vaccine Elicits Reduction of Tumor Clones and Favorable Perturbations in the Immune Microenvironment in Patients (pts) with Untreated Smoldering Waldenström Macroglobulinemia (sWM)

A Novel Therapeutic DNA Vaccine Elicits Reduction of Tumor Clones and Favorable Perturbations in the Immune Microenvironment in Patients (pts) with Untreated Smoldering Waldenström Macroglobulinemia (sWM)

THU0187 IMPACTS OF BODY MASS INDEX ON CLINICAL RESPONSE OF NOVEL SUBCUTANEOUS INFLIXIMAB (CT-P13 SC) IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: 1-YEAR RESULTS FROM A PART 2 OF PHASE I/III RANDOMIZED CONTROLLED TRIAL

Background: In the post-hoc analysis of PLANETRA, a Phase III randomized controlled trial (RCT), no significant association was found between body mass index (BMI) and clinical responses in rheumatoid arthritis (RA) patients using weight-based intravenous (IV) infliximab (3 mg/kg every 8 weeks)1,2. Since the subcutaneous (SC) formulation of CT-P13 which was approved from EMA after demonstrating non-inferiority compared to CT-P13 IV is a fixed-dose of 120 mg biweekly, it is meaningful to evaluate the impact of BMI on clinical response of CT-P13 SC3,4. Objectives: This report is to investigate post-hoc impact of BMI on clinical responses of CT-P13 SC 120 mg in Part 2 of a Phase I/III RCT in active RA patients throughout the 1-year treatment period. Methods: A total of 165 patients who received at least one full dose of CT-P13 SC (after IV induction at Weeks 0 and 2) in the initial treatment stage before Week 30 and who had at least one efficacy evaluation result after Week 6 or thereafter were included in this analysis. Patients were categorized into 3 groups; under/normal weight ( Results: In the under/normal weight (n=63), overweight (n=61), and obesity (n=41) groups, the mean±SD of age (years) (48.7±14.00, 51.5±10.93, 53.8±10.62) and the mean±SD of RA duration (years) (6.4±6.00, 8.2±9.27, 5.4±4.72) were comparable. At baseline, the rates of high disease activity (90.5%, 90.2%, 87.8%; DAS28 [CRP]>5.1) were similar among the groups. All other baseline and disease characteristics including gender, race, and other disease activity parameters were also comparable among the groups. The rate of remission or LDA (Figure 1), the mean change from baseline of DAS28 (CRP) (-3.3, -3.1, -3.3 at Week 54), duration of LDA up to Week 54 (26.2, 29.2, 27.9 weeks), and the good or moderate EULAR responder rates (84.1%, 80.3%, 90.2% at Week 54) were all comparable among the groups and there were no statistically significant differences (p-value>0.05). The ACR responder rates were also comparable among the groups except for the ACR70 at Weeks 2 and 6 which were obtained following 2 IV infusions in the IV dose loading phase. Absolute value of Pearson correlation coefficient was below 0.06 between BMI at screening and mean change from baseline in DAS28 (CRP) during CT-P13 SC treatment from Weeks 14 to 54, indicating that correlation between two measurements was weak and was not statistically significant (p-value>0.05) (Figure 2). Conclusion: These post-hoc results showed that there was no impact of BMI on the clinical responses of CT-P13 SC 120 mg biweekly in RA patients. Therefore, CT-P13 SC 120 mg could be a reasonable therapeutic option regardless of BMI.

THU0194 CHARACTERISATION OF DEPTH OF RESPONSE, INCLUDING 50% IMPROVEMENT IN ACR COMPONENTS AT WEEK 12 AND REMISSION AT WEEK 24, FOLLOWING TREATMENT WITH FILGOTINIB COMPARED WITH METHOTREXATE OR ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: The oral, potent, selective JAK1 inhibitor filgotinib (FIL) showed favorable efficacy at week (W)12 and W24 of treatment for rheumatoid arthritis (RA) compared with methotrexate (MTX) monotherapy (mono) in FINCH 3 (NCT02886728) and with placebo (PBO) or adalimumab (ADA) in FINCH 1 (NCT02889796). Objectives: 50% clinical improvement from baseline at W12 is a key checkpoint for RA treatment.1 These post hoc analyses evaluated FIL treatment effect on improvement in ACR components at W12 and remission at W24 in FINCH 3 and FINCH 1. Methods: FINCH 3 and FINCH 1 were global, phase 3, double-blind studies in patients (pts) with active RA. In FINCH 3, MTX-naive pts were randomised 2:1:1:2 to once-daily (QD) oral FIL 200 mg + weekly MTX, FIL 100 mg + MTX, FIL 200 mg mono + PBO, or PBO + MTX mono up to W52. In FINCH 1, pts with inadequate response to MTX (MTX-IR) on a background of stable MTX were randomised (3:3:2:3) to oral FIL 200 or 100 mg QD, subcutaneous ADA 40 mg Q2W, or PBO up to W52. Post hoc analyses evaluated proportions of pts with 50% improvement from baseline in each ACR component and in all 7 ACR components (ACR50c) at W12, and proportions of pts with ACR50c at W12 achieving clinical remission at W24. Comparisons between treatments were not adjusted for multiplicity; subgroup comparisons are descriptive. Results: Analyses included 1249 pts in FINCH 3 and 1755 pts in FINCH 1. Greater proportions of pts receiving FIL 200 mg + MTX, FIL 100 mg + MTX, or FIL mono (FINCH 3) vs MTX mono (FINCH 3) or PBO + MTX (FINCH 1)—and numerically higher proportions of pts receiving FIL 200 mg + MTX vs FIL 100 mg + MTX (both studies) or ADA + MTX (FINCH 1)—achieved ACR50c and individual components at W12 (Table). Proportions of pts achieving CDAI ≤2.8 (Figure 1) or Boolean remission (Figure 2) at W24 were higher for pts with vs without ACR50c at W12 (Figures 1–2). Conclusion: In MTX-naive and MTX-IR pts with RA, FIL treatment was more effective vs MTX (FINCH 3) or PBO (FINCH 1) for achieving ACR50c at W12—a potential predictor of remission at W24. Proportions of pts achieving ACR50c at W12 were numerically higher for pts receiving FIL 200 mg + MTX vs FIL 100 mg + MTX (both studies) or ADA + MTX (FINCH 1).

THU0192 UPADACITINIB TREATMENT AND THE ROUTINE ASSESSMENT OF PATIENT INDEX DATA 3 (RAPID3) AMONG PATIENTS WITH RHEUMATOID ARTHRITIS

Background: Upadacitinib (UPA) is an oral reversible JAK inhibitor engineered for greater selectivity for JAK1 vs JAK2, JAK3, and TYK2, and is currently being assessed for the treatment of RA. RAPID3 is a pooled index of the three key patient-reported measures: patient global assessment, pain, and physical function. Objectives: In this analysis we assessed the effect of UPA treatment on RAPID3 in the SELECT-BEYOND, SELECT-COMPARE, and SELECT-MONOTHERAPY trials. Methods: In SELECT-BEYOND1, bDMARD-IR pts received UPA 15 mg or 30 mg once daily (QD), or PBO for 12 wks while continuing stable csDMARD therapy. In SELECT-COMPARE2, MTX-IR pts received UPA 15 mg QD, PBO, or ADA 40 mg every 2 wks for 12 wks while continuing MTX. In SELECT-MONOTHERAPY3, pts received UPA monotherapy 15 mg or 30 mg QD, or continued MTX monotherapy (cMTX) for 14 wks. We assessed the least squares mean changes from baseline (BL) in RAPID3 and the proportion of pts reporting RAPID3 remission (≤3), low (LDA, >3 to ≤6), moderate (MDA, >6 to ≤12), and high disease activity (HDA, >12). Correlations between RAPID3 remission and remissions defined by CDAI, SDAI, and DAS28(CRP) were also assessed using Pearson correlation coefficients. Non-responder imputation was used for categorical endpoints, and last observation carried forward for continuous endpoints in pts who received rescue therapy in SELECT-COMPARE. Other continuous data are as observed. Data were analyzed descriptively. Results: 498, 648, and 1629 pts were randomized in SELECT-BEYOND, -MONOTHERAPY, and -COMPARE, respectively. Numerically higher improvements from BL in RAPID3 were reported with UPA 15 mg and 30 mg treatment vs PBO in SELECT-BEYOND, and vs cMTX in SELECT-MONOTHERAPY (Table). UPA 15 mg QD was also associated with greater reductions from baseline in RAPID3 vs PBO and ADA in SELECT-COMPARE (Table). Of note, the improvements in RAPID3 with UPA and ADA exceeded the minimal clinically important difference (MCID = 3.84). The proportions of pts achieving RAPID3 remission were numerically higher in the UPA 15 mg and 30 mg groups vs PBO and cMTX in SELECT-BEYOND and SELECT-MONOTHERAPY, respectively (Figure). In addition, the proportions of pts in RAPID3 HDA were lower with UPA vs PBO and cMTX in these trials. In SELECT-COMPARE, higher rates of RAPID3 remission, with fewer pts in HDA, were evident with UPA 15 mg treatment vs PBO and ADA (Figure). Correlations between RAPID3 and other remission endpoints were significant (p Conclusion: UPA was associated with improvements in RAPID3, both as monotherapy and in combination, in MTX-IR (SELECT-COMPARE and SELECT-MONOTHERAPY) or bDMARD-IR (SELECT-BEYOND) pts. UPA treatment can result in improved patient-reported disease activity, pain, and physical function in RA. Disclosure of Interests: Martin Bergman Shareholder of: Johnson & Johnson – stockholder, Consultant of: AbbVie, BMS, Celgene Corporation, Genentech, Janssen, Merck, Novartis, Pfizer, Sanofi – consultant, Speakers bureau: AbbVie, Celgene Corporation, Novartis, Pfizer, Sanofi – speakers bureau, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Sami Bahlas: None declared, Mira Ali Shareholder of: AbbVie, Employee of: AbbVie, Sebastian Meerwein Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB

AB1185 BUDGET IMPACT ANALYSIS OF INTRODUCING SUBCUTANEOUS INFLIXIMAB CT-P13 SC FROM THE UK PAYER PERSPECTIVE

Background:CT-P13 subcutaneous (SC) is the first and only SC version of infliximab developed by Celltrion Healthcare and currently approved by the European Medicines Agency (EMA) for the treatment of rheumatoid arthritis (RA). Infliximab has been only available in intravenous (IV) formulation and thus this new mode of administration will allow patients to self-inject at homes. Self-injection will reduce number of outpatient visits and expected to decrease IV administration cost significantly. This research describes the economic impact of introducing infliximab SC from the UK payer perspective.Objectives:The budget impact analysis (BIA) was conducted to assess the financial impact of the adoption of infliximab SC. The BIA calculates the costs of treatment (drug acquisition cost and administration) for patients with RA as first-line treatments, and compares the cost in a scenario without infliximab SC vs a scenario with infliximab SC to estimate the budget impact over the 5 year period.Methods:A prevalence-based BIM was developed incorporating epidemiological data, administration cost data from the literature and market share data from IQVIA. The analysis compared a market scenario where a proportion of patients were treated with infliximab SC (‘World With’ infliximab SC) to an alternative market scenario where infliximab SC were not available and all patients were treated with IV (‘World Without’ infliximab SC). The model assumed that the clinical outcomes are same between infliximab SC and infliximab IV, and patients entering the model were all naïve and remained in the treatment for 5 years. In the ‘World With’ scenario, patients receiving infliximab IV switched to SC administration at 30% in Year 1, 45% in Year 2, and remained 60% from Year 3 to 5. The drug cost of infliximab SC is assumed to be the same as that of comparator treatments. Administration cost per infliximab IV infusion was estimated to be ₤382 and ₤3.32 per SC administration.Results:Compared to the “World Without” infliximab SC, the introduction of subcutaneous infliximab resulted in cost savings of ₤39.6 million in UK over a 5-year period, equating to 4,466 additional patients to be treated with infliximab SC in base case scenario.Sensitivity analysis includes dose-escalation up to 5mg/kg to reflect the real-world setting. In that scenario, the saving increases to ₤279.6 million over a 5-year period, equating to 30,839 additional patients to be treated with infliximab SC.Conclusion:Utilization of subcutaneous infliximab may lead to substantial cost savings for UK payers. Self-injection will significantly reduce the burden on healthcare delivery allowing resource to be spent elsewhere. Sensitivity analysis concluded that treatment with increased IV dose will result in higher savings from switching patients to subcutaneous infliximab.

P242 CZP improves work and household productivity and social participation over 1 year of treatment in patients with non-radiographic axSpA

Abstract Background Certolizumab pegol (CZP) treatment has been shown to significantly improve work and household productivity and social participation compared to placebo in active non-radiographic axial spondyloarthritis (nr-axSpA) patients up to 24 weeks. Here, we report the impact of CZP in combination with non-biologic background medication (NBBM) on signs and symptoms of nr-axSpA compared to placebo+NBBM. Methods C-axSpAnd (NCT02552212) is a 3-year, phase 3, multicentre study including a 52-week double-blind, placebo-controlled period (completed). Patients had active nr-axSpA, objective signs of inflammation (OSI; elevated CRP and/or positive MRI of the sacroiliac joint), previous inadequate response to ≥ 2 NSAIDs and were randomised 1:1 to CZP (400 mg at Weeks 0/2/4, then 200 mg every 2 weeks) or placebo. The validated arthritis-specific Work Productivity Survey (WPS) assessed the impact of nr-axSpA on work and household productivity and social participation. Missing data were imputed using last observation carried forward (LOCF) post hoc in the Full Analysis Set (randomised patients who received ≥1 dose of CZP). Results 317 patients were randomised (CZP: 159; placebo: 158). Mean age at baseline was 37.3 years and 51.4% of patients were female. At baseline, most patients were employed (CZP: 124 [77.8%]; placebo: 123 [78.0%]) and reported a mean 3.7 (CZP) and 3.5 (placebo) workdays missed per month due to disease (Table 1). By Week 12, work absenteeism substantially improved in the CZP group compared with placebo (0.9 vs 2.1 days missed per month, LOCF), with further improvements at Week 52 (0.3 vs 2.0 days missed per month, LOCF). Between Week 12 and Week 52, most placebo patients (104, 65.8%) switched to open-label CZP, impacting Week 52 imputed outcomes. Despite this, similar patterns of improvement following CZP treatment were seen for absenteeism, workdays with impaired productivity, household days with missed/reduced productivity and social participation between imputed and observed case data (Table 1). Improvements were similar between male and female patients (data not shown). Conclusion CZP treatment resulted in improvements in work and household productivity and social participation for nr-axSpA patients as early as Week 12 compared to background medication only, with benefits maintained to Week 52. Disclosures K. Gaffney: Other; Research Grants/Consultancy Fees from Abbvie, Biogen, Celgene, Gilead, Izana, Janssen, Lilly, Novartis, Pfizer, UCB Pharma. A. Deodhar: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith and Klein, Janssen, Novartis, Pfizer and UCB. Grants/research support; BMS, Eli Lilly, Glaxo Smith &amp; Kline, Janssen, Novartis, Pfizer and UCB. L. Gensler: Consultancies; Galapagos, Eli Lilly and Janssen. Grants/research support; AbbVie, Amgen, Novartis, UCB Pharma. J. Kay: Consultancies; AbbVie, Boehringer Ingelheim, Celltrion Healthcare, Horizon Therapeutics, Merck Sharp &amp; Dohme, MorphoSys, Novartis, Pfizer, Samsung Bioepis, Sandoz and UCB Pharma. Grants/research support; Gilead Sciences, Novartis AG, Pfizer and UCB Pharma. W. Maksymowych: Other; Consultant and/or speaker fees and/or grants from AbbVie, Amgen, Eli Lilly, Janssen, Merck, Pfizer, Synarc, Sanofi and UCB Pharma. N. Haroon: Consultancies; Abbvie, Amgen, Eli Lilly, Janssen, Novartis and UCB Pharma. R. Landewé: Consultancies; Abbott, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth. Member of speakers’ bureau; Abbott, Amgen, Bristol Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth. Grants/research support; Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth. M. Rudwaleit: Consultancies; Abbott, Bristol-Myers Squibb, Janssen, MSD, Pfizer, Roche, UCB Pharma. S. Hall: Other; Consulting fees/ research grants from AbbVie, Eli Lilly, Novartis, and UCB Pharma. L. Bauer: Other; Employee of UCB Pharma. B. Hoepken: Other; Employee of UCB Pharma. N. de Peyrecave: Other; Employee of UCB Pharma. T. Kumke: Other; Employee of UCB Pharma. D. van der Heijde: Consultancies; AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. Other; Director of Imaging Rheumatology BV.

P284 Certolizumab pegol-treated patients with non-radiographic axSpA demonstrate improvements in sleep quality and other patient reported outcomes

Abstract Background Certolizumab pegol (CZP) treatment has demonstrated improvements in multiple manifestations of non-radiographic axial spondyloarthritis (nr-axSpA), including patient-reported outcomes (PROs). Here, we report PROs for nr-axSpA patients treated with CZP or placebo in CaxSpAnd - the first 52-week placebo-controlled study to investigate the efficacy of an anti-TNF agent in patients with active nr-axSpA and objective signs of inflammation. Methods C-axSpAnd (NCT02552212) is a 3-year, phase 3, multicenter study including a 52-week double-blind, placebo-controlled period (completed); patients who had an inadequate response to ≥ 2 non-steroidal anti-inflammatory drugs were randomized 1:1 to placebo or CZP (400mg at Weeks 0/2/4, then 200mg every 2 weeks). Clinical PROs included: Sleep Problems Index scores I (6 items) and II (9 items) from the Medical Outcomes Study Sleep Scale (assesses sleep disturbance, adequacy, somnolence, quantity, snoring, and awakening short of breath or with a headache), nocturnal spinal pain (numerical rating scale [NRS]), fatigue (BASDAI Q1), and morning stiffness (average of BASDAI Q5 + 6). Post-hoc analyses of minimal clinically important differences (MCID [≥1-point improvement]) for fatigue and nocturnal spinal pain were conducted. Variables were analyzed using an ANCOVA model including baseline score as a covariate and fixed effects for treatment group, region and MRI/CRP classification. P-values were nominal. Missing values following discontinuation of double-blind treatment were imputed using last observation carried forward. Results 317 patients with nr-axSpA were randomised to CZP (n = 159) or placebo (n = 158); 125 (79%) and 54 (34%) patients, respectively, completed Week 52. CZP-treated patients showed greater improvements (indicated by higher scores) in Sleep Problems Index II scores vs placebo-treated patients at Week 12 (mean change from baseline: 4.8 [CZP] vs 2.2 [placebo]; p &amp;lt; 0.001). Improvements were also seen in other clinical PROs (Table). By Week 12, greater proportions of patients treated with CZP vs placebo experienced at least MCID response in fatigue (85.4% vs 57.6%, respectively) and nocturnal spinal pain (82.8% vs 58.9%, respectively); results were sustained through Week 52. Conclusion CZP-treated nr-axSpA patients showed substantial improvements in sleep quality and other clinical outcomes important to patients; future analyses of these data will explore associations between sleep quality and other clinical PROs. Disclosures R. Sengupta: Other; R.S. has received speaker fees, support for conference attendance and grants from Abbvie, Biogen, Celgene, Novartis, Pfizer and UCB Pharma. L. Gensler: Grants/research support; AbbVie, Amgen, Novartis, UCB Pharma; consulting fees from Galapagos, Eli Lilly and Janssen. J. Kay: Consultancies; AbbVie, Boehringer Ingelheim, Celltrion Healthcare, Horizon Therapeutics, Merck Sharp &amp; Dohme, MorphoSys, Novartis, Pfizer, Samsung Bioepis, Sandoz and UCB Pharma. Grants/research support; Gilead Sciences, Novartis AG, Pfizer and UCB Pharma. W. Maksymowych: Other; Consultant and/or speaker fees and/or grants from AbbVie, Amgen, Eli Lilly, Janssen, Merck, Pfizer, Synarc, Sanofi and UCB Pharma. N. Haroon: Consultancies; Abbvie, Amgen, Eli Lilly, Janssen, Novartis and UCB Pharma. L. Bauer: Other; Employee of UCB Pharma. B. Hoepken: Other; Employee of UCB Pharma. N. de Peyrecave: Other; Employee of UCB Pharma. T. Kumke: Other; Employee of UCB Pharma. A. Deodhar: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith and Klein, Janssen, Novartis, Pfizer and UCB. Grants/research support; BMS, Eli Lilly, Glaxo Smith &amp; Kline, Janssen, Novartis, Pfizer and UCB.