UCB Pharma (Spain)

Abstract Background/Aims In patients with rheumatoid arthritis (RA), high rheumatoid factor (RF) titres are considered a poor prognostic factor and are associated with higher disease activity, risk of radiographic progression and decreased response to TNF inhibitors (TNFis). Recent data suggests that patients with RA and high RF titre may achieve and maintain greater clinical improvement with TNFis without a crystallisable fragment (Fc) compared to TNFis with an Fc. In this analysis of the EXXELERATE trial, we assessed efficacy outcomes of certolizumab pegol (CZP), a PEGylated Fc-free TNFi, versus adalimumab (ADA; Fc-containing TNFi) in patients with RA and high RF titres. Methods The phase 4 EXXELERATE trial (NCT01500278) compared the efficacy and safety of CZP to ADA. Patients were randomised 1:1 to CZP 200 mg every two weeks (Q2W) plus methotrexate (MTX) or ADA 40 mg Q2W plus MTX. At Week 12 (Wk), patients were classified as responders or non-responders; non-responders were switched to the other TNFi with possible follow-up to Wk104. Here, we report drug plasma concentrations, mean disease activity score (DAS)28-CRP score and proportion of patients achieving low disease activity (LDA; threshold: DAS28-CRP ≤2.7) to Wk104. Results are stratified by RF titre quartile (≤Q3: ≤203 IU/mL; >Q3: >203 IU/mL; measured by Roche Tina-quant®) and reported as observed data. Results Baseline data by RF quartile were available for 453 CZP-randomised patients (≤Q3: n = 334; >Q3: n = 119) and 454 ADA-randomised patients (≤Q3: n = 347; >Q3 n = 107). Baseline characteristics were similar between CZP- and ADA-randomised patients across the RF titre quartiles. At Wk12, 66 CZP-treated patients switched to ADA and 59 ADA-treated patients switched to CZP. At Wk104, mean ADA concentrations were 22.9% lower in patients with RF >Q3 (mean [SD] 4.8 [3.0]) vs those with RF ≤Q3 (6.2 [4.0]); in CZP-treated patients, this difference was smaller (13.0%) in patients with RF >Q3 (23.3 [15.4]) vs those with RF ≤Q3 (26.7 [13.1]). For patients in RF ≤Q3, mean DAS28-CRP scores were similar between CZP- and ADA-treated patients through Wks0-104 (mean [SD] DAS28 at Wk104: 2.48 [1.18] CZP vs 2.49 [1.14] ADA). However, for patients in RF >Q3, mean [SD] DAS28-CRP scores were nominally lower in CZP- vs ADA-treated patients (Wk104: 2.50 [1.18] CZP vs 2.93 [1.22] ADA). A similar pattern was observed for the proportion of patients achieving LDA at Wk104 (≤Q3: 64.8% CZP vs 65.1% ADA; >Q3: 65.7% CZP vs 48.3% ADA). Conclusion CZP-treated patients with RA and high titre RF had similar drug concentrations and clinical responses to patients with RA and low titre RF, a pattern not observed in ADA-treated patients. These data, together with previous reports where CZP showed consistent efficacy irrespective of baseline RF titre, suggest CZP may be a suitable therapy for patients with RA and high RF titre. Disclosure J.S. Smolen: Honoraria; AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, R-Pharma, Roche, Samsung, Sanofi, and UCB Pharma. Grants/research support; AbbVie, AstraZeneca, Eli Lilly, Novartis and Roche. Other; Editor of Annals of the Rheumatic Diseases, Co-editor of Rheumatology 7E/8E, Convenor of EULAR Task Forces and T2T Task Forces. P.C. Taylor: Consultancies; AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead, GSK, Janssen, Nordic Pharma, Pfizer, Sanofi and UCB Pharma. Grants/research support; Galapagos. Y. Tanaka: Honoraria; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho, Taisho. Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho. Grants/research support; Chugai, Eisai, Mitsubishi-Tanabe, Taisho. C. Cara: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. B. Lauwerys: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. R. Xavier: Consultancies; AbbVie, AstraZeneca, Janssen, Organon, UCB Pharma. Member of speakers’ bureau; AbbVie, AstraZeneca, Janssen, Organon, and UCB Pharma. J.R. Curtis: Consultancies; AbbVie, Amgen, BMS, Corrona, Crescendo, Genentech, Janssen, Pfizer, Roche, UCB Pharma. Grants/research support; AbbVie, Amgen, BMS, Corrona, Crescendo, Genentech, Janssen, Pfizer, Roche, UCB Pharma. T.R. Mikuls: Consultancies; Horizon Therapeutics, Pfizer, Sanofi, UCB Pharma. Royalties; Elsevier, Wolters Kluwer Health (UpToDate). Grants/research support; Horizon Therapeutics. M. Weinblatt: Consultancies; AbbVie, Aclaris, Amgen, Aqtual, BMS, CorEvitas, Eli Lilly, GSK, Gilead, Horizon, Johnson and Johnson, Prometheus, Pfizer, Rani, Revolo, Sanofi, Scipher, Sci Rhom, Set Point, UCB Pharma. Grants/research support; AbbVie, Aqtual, BMS, Janssen.

Antecedentes La espondiloartritis axial no radiográfica (EspAax-nr) es una enfermedad que reduce la capacidad funcional y la calidad de vida de las personas afectadas con esta patología, influyendo negativamente en su capacidad productiva. El objetivo de este estudio fue estimar el impacto económico sobre la productividad laboral (PL; costes indirectos) y la productividad doméstica (PD, costes directos no sanitarios) en pacientes con EspAax-nr tratados con certolizumab pegol (CZP) en combinación con la terapia estándar no biológica (TNB) frente a la TNB, según la perspectiva social en España. Métodos Se desarrolló un modelo de análisis de costes para estimar los costes relacionados con la PL y PD. Los datos de productividad se obtuvieron del ensayo clínico C-axSpAnd (NCT02552212) que comparaba CZP/TNB frente a TNB durante 52 semanas en 317 pacientes. Para valorar la pérdida de PL y PD se consideró el número de días perdidos por mes y los días por mes con productividad reducida ≥ 50%, debido a la EspAax-nr. El coste de una jornada laboral perdida (86,44€/día; €2019) se obtuvo del Instituto Nacional de Estadística, considerando los costes laborales. Para determinar el coste de la PD, se asumió que, si el paciente no podía realizar las actividades domésticas, se requeriría un cuidador o personal externo, con un coste/día igual al salario mínimo interprofesional (31,21€/día; €2019). Resultados Los costes mensuales derivados de la pérdida de PL por paciente tratado con CZP/TNB y TNB fueron de 159,91€ y 419,22€, respectivamente. El tratamiento con CZP/TNB proporcionaría ahorros, en términos de pérdida de PL evitada, de 259,31€/mes y 3.111,70€/año. La pérdida de PD en pacientes tratados con CZP/TNB implicaría 137,33€ frente a 248,13€ con TNB al mes, lo que generaría un ahorro de 110,80€/mes y 1.329,61€/año en pacientes tratados con CZP/TNB. El tratamiento total con CZP/TNB frente a TNB proporcionaría un ahorro anual medio de 4.441,31€/paciente. Conclusión Existe escasa información del impacto de las terapias biológicas sobre la carga económica, desde la perspectiva social, relacionada con los beneficios en la productividad. Los resultados de este análisis sugieren que, en España, el tratamiento de la EspAax-nr con CZP/TNB, en comparación con TNB, podría generar ahorros para la sociedad y para el paciente debido a la ganancia de PL y de PD, respectivamente. Palabras clave certolizumab pegol, espondiloartritis axial no radiográfica, productividad laboral, productividad doméstica, perspectiva social.

ABSTRACTAim: This study evaluated the effect of ≥6 months of transdermal rotigotine on non-motor and motor symptoms of patients with advanced Parkinson's disease. Materials and methods: The study was conducted in Spain between September 2011 and December 2012 (ClinicalTrials.gov: NCT01504529). The primary efficacy variable was the change from baseline in non-motor symptoms, as assessed by changes in Parkinson's Disease Non-Motor Symptoms Questionnaire total scores at 6 months. Secondary endpoints included the assessment of motor symptoms by Unified Parkinson's Disease Rating Scale III scores. Results: Data from 378 patients (mean age: 70.2 years; 56.9% male) with Parkinson's disease receiving rotigotine from were collected. Mean disease duration was 6.1 years, and mean rotigotine treatment duration was 45.6 months. Rotigotine reduced non-motor symptoms by 14.6% (mean change from baseline in Parkinson's Disease Non-Motor Symptoms Questionnaire: −1.5 ± 3.4; p < 0.0001). The majority of patients (58.2%) had improved non-motor symptoms at 6 months. Comparing the baseline versus study end, fewer patients experienced events in the urinary (78.6% vs. 73.3%; p = 0.0066), sleep (82.8% vs. 72.8%; p < 0.0001) and mood/cognition (77.3% vs. 66.4%; p < 0.0001) domains of the Parkinson's Disease Non-Motor Symptoms Questionnaire. Mean motor symptoms were reduced from baseline by 8.0% (mean change from baseline in Unified Parkinson's Disease Rating Scale III: −2.6 ± 8.0; p < 0.0001). Conclusions: In clinical practice in Spain, rotigotine may be an effective treatment to reduce the non-motor and motor symptoms in patients with advanced Parkinson's disease.