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Purpose The purpose of this study is to analyze interlocking directorate (ID) networks of family and nonfamily firms (FFs) in Chile, Mexico and Peru. Design/methodology/approach Social network analysis methodology allowed us to analyze the position of FFs within the structure of IDs at the local and transnational levels. Findings FFs tend to have a higher proportion of board interlocks to other firms, especially FFs. In addition, FFs are more likely to occupy a brokerage position in national IDs structures. Finally, they also have a higher proportion of interlocks to other domestic firms in and nearby geographic areas. Thus, they create transnational networks. Originality/value This paper finds evidence that supports three of the premises of interorganizational familiness literature (Lester and Cannella, 2006). FFs are part of national as well as international corporate networks more than other types of firms, through interlocking directorships.

PurposeThe purpose of this paper is to understand the influence of family ownership and governance mechanisms on corporate social responsibility (CSR) scores through the lens of the principal–principal (PP) perspective.Design/methodology/approachUsing a random-effects model the authors sample 21 hundred board members across a 101 listed Mexican companies from 2008 to 2020.FindingsThe paper finds that board independence and board committees are positively related to CSR scores.Practical implicationsResults of this paper suggest that stronger governance can enhance CSR: board independence and committees can be a counterbalancing mechanism serving stakeholders aiming to improve CSR scores.Originality/valueMost CSR research has focused on determinants and outcomes of CSR. The authors analyze an unexplored aspect of the corporate governance (CG) and CSR relationship: the potential influence of family ownership and governance mechanisms on CSR.

To understand if certain board traits can contribute to attract CEO directors,Panel data model with firm fixed effects of individual and firm level attributes from 450 public firms in Argentina, Brazil, Chile, Colombia, Mexico and Peru,Higher levels of masters abroad, board ties, government experience and foreign members are all negatively related to the appointment of CEO directors,The use of non-performance outcome variable such as CEO experience in the family led emergent environment of Latin America,Entender si hay caracteristicas de un consejo que ayudan a atraer consejeros CEOs,Modelo con datos panel y efectos fijos usando informacion individual y de empresa de 450 empresas publicas en Argentina, Brasil, Chile, Colombia, Mexico y Peru,Mayores niveles de maestrias en el extranjero, lazos de consejo, experiencia de gobierno y presencia de extranjeros estan relacionados negativamente con el nombramiento de nuevos consejeros CEOs,El uso de una variable que no es de desempeno como experiencia de CEOs en el contexto de empresa familiar en Latinoamerica

Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation. Methods Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM® MarketScan® Commercial and Medicare Supplemental US insurance claims databases (March 2016–October 2018). Second, using data collected in the Corrona US RA Registry (February 2016–August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions. Results In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses. Conclusion These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA. Trial Registration Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020. Electronic supplementary material The online version of this article (10.1007/s12325-020-01501-z) contains supplementary material, which is available to authorized users.

Background/objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD. Methods This post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as "probable" (supportive clinical evidence) or "possible" (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events. Results Of 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13-5.21]), current smokers (2.89 [1.33-6.26]), and Disease Activity Score in 28 joints-erythrocyte sedimentation rate score (1.30 [1.04-1.61]) as significant risk factors for ILD events. Conclusions Across P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA.

Summary Background Tofacitinib is an oral Janus kinase (JAK) inhibitor used for the treatment of rheumatoid arthritis. We assessed the efficacy and safety of tofacitinib after methotrexate withdrawal in patients who achieved low disease activity (LDA) with tofacitinib in combination with methotrexate. Methods ORAL Shift was a phase 3b/4 non-inferiority trial in patients aged at least 18 years with moderate-to-severe rheumatoid arthritis and an inadequate response to methotrexate done in 109 centres across 16 countries. After 24 weeks of open-label tofacitinib modified-release 11 mg once daily plus methotrexate, patients who achieved LDA (clinical disease activity index [CDAI] ≤10) were randomly assigned 1:1 via an automated web-based response system to receive tofacitinib plus placebo (tofacitinib monotherapy; ie, masked methotrexate withdrawal) or continue tofacitinib plus methotrexate for 24 weeks in a double-blind manner. The primary endpoint was the least squares mean change from week 24 to week 48 in disease activity score in 28 joints with four variables, including erythrocyte sedimentation rate (DAS28-4[ESR]). The primary analysis was done in all patients who received at least one dose of study treatment in both phases, and safety was assessed in all patients who received at least one dose of study treatment since enrolment. Non-inferiority of tofacitinib monotherapy versus tofacitinib plus methotrexate was declared if the upper bound of the 95% CI for the difference in change in DAS28-4(ESR) between treatment groups was less than 0·6. Safety was assessed in both phases. The trial is registered with ClinicalTrials.gov , NCT02831855 , and is complete. Findings Between Sept 1, 2016, and Nov 1, 2017, 694 patients were enrolled in the open-label phase and 623 received study treatment for 24 weeks. 533 achieved CDAI-defined LDA and were randomly assigned into the double-blind phase (267 in the tofacitinib monotherapy group and 266 in the tofacitinib plus methotrexate group). Three participants in the monotherapy group did not start treatment so were not included in the primary analysis. Non-inferiority was demonstrated (difference 0·30 [95% CI 0·12–0·48]). 107 (41%) of 264 patients in the tofacitinib monotherapy group and 109 (41%) of 266 in the tofacitinib plus methotrexate group had adverse events; five patients from each group discontinued because of adverse events; two patients died in the tofacitinib plus methotrexate group. No new safety findings were reported up to 48 weeks. Interpretation Patients with rheumatoid arthritis who achieve LDA with a combination of tofacitinib plus methotrexate may consider withdrawing methotrexate without significant worsening of disease activity or unexpected safety issues. Funding Pfizer.

The purpose of this paper is to analyze the differential effects that institutions have on country IPO activity.,With a sample of 64 countries over a 15-year period (2000-2014), the authors test the variables rule of law, uncertainty avoidance and masculinity on subsamples of developed (27) and emerging (37) countries to explore their influence on domestic IPO activity level.,For developed countries, only uncertainty avoidance and masculinity are significant. Within emerging countries, it is uncertainty avoidance and rule of law that are significant.,Using different country classification frameworks could yield more detailed and focused results on the influence that country-level variables have on IPO activity.,Multinational firms could use these findings for decisions related to their potential subsidiary IPOs.,This is a novel empirical work relating institutions to IPO activity, using emerging and developed country subsamples. It also focuses on IPO activity instead of IPO underpricing/performance and contributes to extend the scope of the IPO literature to global non-Anglo contexts.,Analizar los efectos diferenciales que las instituciones tienen en OPIs (ofertas publicas iniciales) a nivel pais.,En una muestra de 64 paises en un periodo de 15 anos (2000-14) probamos las variables: estado de derecho, aversion a la incertidumbre y masculinidad en submuestras de paises: desarrollados (27) y emergentes (37) para explorar su influencia en el numero de OPIs a nivel pais.,En paises desarrollados la aversion a la incertidumbre y masculinidad son significativas. Dentro de paises emergentes, la aversion a incertidumbre y estado de derecho son significativas.,Usar diferentes metodos para clasificar paises podria resultar en resultados mas detallados y enfocadas para entender la influencia que variables a nivel pais tienen en el nivel de OPIs.,Empresas multinacionales podrian usar estos resultados para decisiones relacionadas a sus subsidiarias potenciales.,Este es un trabajo novedoso que relaciona a las instituciones con la actividad OPI usando submuestras de paises desarrollados y emergentes. Tambien se enfoca en actividad OPI en lugar de subvaluacion/desempeno OPI y contribuye a extender la literatura OPI a contextos no anglo sajones.,Este articulo se pudo hacer gracias al apoyo parcial de la Asociacion Mexicana de Cultura A.C.,OPIs, Emergentes, Desarrollados, Instituciones and Cultura,Analisar os efeitos diferenciais que as instituicoes tem na atividade de IPO (Oferta publica inicial en ingles) dos paises.,Em uma amostra de 64 paises em um periodo de 15 anos (2000-14). Testamos as variaveis: estado de direito, evitacao de incerteza e masculinidade em subamostras de paises desenvolvidos (27) e, emergentes (37) para explorar sua influencia no nivel de atividade domestico do IPO.,Para os paises desenvolvidos, apenas a evitacao de incertezas e a masculinidade sao significativas. Nos paises emergentes, a evitacao de incertezas e o estado de direito sao significativos.,O uso de diferentes estruturas de classificacao de paises poderia produzir resultados mais detalhados e focados na influencia que as variaveis de nivel de pais tem na atividade de IPO.,As empresas multinacionais poderiam usar essas descobertas para decisoes relacionadas a seus possiveis IPOs subsidiarios.,Este e um novo trabalho empirico que relaciona instituicoes a atividade de IPO usando subamostras de paises emergentes e desenvolvidos. Tambem se concentra na atividade de IPO, em vez da infravaloracion/performance do IPO, e contribui para estender a literatura do âmbito IPO para os contextos globais nao-anglo.,IPOs, Emergentes, Desenvolvidos, Instituicoes, Cultura

We read with great interest the ACR’s COVID‐19 Vaccine Clinical Guidance Summary for Patients with Rheumatic and Musculoskeletal Diseases (1). We commend the Task Force’s emphasis on the importance of immunization in this population and for providing guidance to the rheumatology community. Regarding their recommendation to hold Janus kinase (JAK) inhibitors for 1 week after each COVID‐19 vaccine dose (1), we propose the following available tofacitinib data for consideration in this context.

Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5-year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease-modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry. Methods IRs (number of first events/100 patient-years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow-up through January 31, 2019). Propensity score (PS) methods were used to control for nonrandom prescribing practices. Hazard ratios (HRs) were calculated to compare rates using multivariable-adjusted Cox regression. Different risk windows were used for acute (MACE, SIEs, HZ, and venous thromboembolic events [VTEs]) and long-term (malignancy and death) events. VTEs were assessed descriptively. Results For MACE, SIEs, and HZ, 1999 (3152.1 patient-years) and 8358 (12 869.4 years) tofacitinib and bDMARD initiators were included, respectively; for malignancy/death, 1999 (4505.6 patient-years) and 6354 (16 670.8 patient-years) initiators were included, respectively. AE rates were similar across cohorts, except for HZ, which was significantly higher with tofacitinib versus bDMARDs (PS-trimmed adjusted HR 2.32; 95% confidence interval [CI] 1.43-3.75). There were 45 (zero serious) and 88 (five serious) HZ events with tofacitinib and bDMARDs, respectively. Sensitivity analyses demonstrated similar results. VTE IRs (95% CI) were 0.29 (0.13-0.54) and 0.33 (0.24-0.45) for tofacitinib and bDMARDs, respectively. Conclusion In this registry analysis, both cohorts had similar MACE, SIE, malignancy, death, and VTE rates; HZ rates were higher for tofacitinib initaitors than for bDMARD initiators.

The purpose of this paper is to examine the factors that affect the likelihood of being public using a comprehensive database of private and public companies in Mexico, from all sectors, during 2006-2014.,The authors estimate a longitudinal probit model to identify the ex ante characteristics of public Mexican firms that differentiate them from those Mexican firms that continue to remain private.,The authors find that larger, younger and less levered Mexican firms are more likely to be public in Mexico. They additionally test the influence of market conditions and location on the probability of being public. They find that location matters but they find no evidence that initial public offerings (IPOs) are driven by favorable Mexican market conditions.,This paper contributes to the Mexican and international literature on IPOs because it uses an original database built from information of private and public Mexican firms. The study contributes to a better understanding of the determinants of the decision of going public in Mexico.,En este articulo se examinan los factores que afectan la probabilidad de que una empresa salga a Bolsa, utilizando una base de datos integral de empresas privadas y publicas en Mexico, de todos los sectores, durante 2006-2014.,Se estima un modelo probit longitudinal para identificar las caracteristicas ex-ante de las empresas mexicanas listadas en bolsa que las diferencian de aquellas que siguen siendo privadas.,Los autores encuentran que las empresas mexicanas mas grandes, jovenes y menos apalancadas tienen mas probabilidades de estar listadas en la bolsa mexicana. Ademas, prueban si hay influencia de las condiciones del mercado y la ubicacion en la probabilidad de listarse. Ellos encuentran que la ubicacion de las empresas importa, pero no encuentran evidencia de que las OPIs sean impulsadas por condiciones favorables del mercado mexicano.,Este trabajo de investigacion contribuye a la literatura mexicana e internacional sobre OPIs, ya que utiliza una base de datos original construida a partir de informacion de empresas mexicanas privadas y publicas. El estudio contribuye a una mejor comprension de los determinantes de la decision de listar una empresa en bolsa en Mexico.

Background:The Phase 3b/4 study ORAL Shift (NCT02831855) demonstrated sustained efficacy/safety of tofacitinib modified-release 11 mg QD following MTX withdrawal, that was non-inferior to continued tofacitinib + MTX use, in patients (pts) with moderate to severe RA who achieved LDA with tofacitinib + MTX at Week (W)24.1Objectives:To assess differences and similarities in clinical/functional responses in pts receiving tofacitinib ± MTX in ORAL Shift.Methods:In ORAL Shift, pts received open-label tofacitinib + MTX to W24; at W24, pts who achieved CDAI LDA were randomised to receive tofacitinib + MTX or tofacitinib + placebo (PBO) from W24–48. In this post hoc analysis, clinical efficacy endpoints were ACR-N (minimum % change from baseline [BL; Δ] at W48 achieved by each pt in 3 efficacy measures), ΔDAS28-4(ESR), and DAS28-4(ESR) remission/LDA (scores ≤3.2) and moderate/high disease activity (scores >3.2). Functional efficacy endpoints were ΔHAQ-DI and HAQ-DI clinically relevant functional progression (CRFP) status at W48, defined as failure to achieve improvement in HAQ-DI ≥ minimum clinically important difference (MCID; ≥0.22 decrease from BL in HAQ-DI). Thus, CRFP was defined as W24–48 were assessed by response subgroups.Results:266 pts receiving tofacitinib + MTX and 264 pts receiving tofacitinib + PBO in W24–48 were included. At W48: mean ACR-N was numerically greater with tofacitinib + MTX vs tofacitinib + PBO (60.8 vs 53.1); mean decrease in HAQ-DI was generally similar between groups (-0.71 vs -0.67); mean decrease in DAS28-4(ESR) was numerically greater with tofacitinib + MTX vs tofacitinib + PBO (-2.95 vs -2.68). The differences/similarities between groups in ACR-N and ΔHAQ-DI were also seen in cumulative probability plots (Figure 1). CRFP rates were numerically lower with tofacitinib + MTX (18.7%) vs tofacitinib + PBO (23.5%), and in pts with remission/LDA (tofacitinib + MTX, 12.1%; tofacitinib + PBO, 16.8%) vs moderate/high disease activity (tofacitinib + MTX, 26.2%; tofacitinib + PBO, 30.8%). Median of mean CRP over time was generally numerically lower in pts with CRFP vs non-CRFP and DAS28-4(ESR)-defined remission/LDA vs moderate/high disease activity; and in those receiving tofacitinib + PBO vs tofacitinib + MTX, irrespective of CRFP or DAS28-4(ESR) disease status (Table 1).Table 1.Median of mean CRPa up to W48 by response subgroupsTofacitinib 11 mg QD + MTXTofacitinib 11 mg QD + PBOMean CRP,amedian (IQR) [n]>BL–W24>W24–48>BL–W24>W24–48HAQ-DI CRFP2.84 (1.15–7.30)2.30 (0.82–4.75)1.45 (0.77–4.42)2.28 (0.53–7.28)[45][46][56][56]HAQ-DI non-CRFP2.81 (1.09–6.19)2.91 (1.19–5.84)2.26 (0.98–4.63)2.47 (1.13–5.53)[195][195][176][178]DAS28-4(ESR) remission/LDA2.48 (1.05–4.95)2.46 (1.07–4.76)1.70 (0.89–4.14)1.95 (0.81–3.82)[126][127][115][117]DAS28-4(ESR) moderate/high disease activity3.56 (1.17–7.13)3.58 (1.36–8.33)2.60 (0.87–5.16)2.68 (1.34–8.23)[107][107][115][115]aMean CRP was calculated as the average CRP value during each time period (>BL–W24 or >W24–48)CRP, C-reactive protein; DAS28-4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire-Disability Index; IQR, interquartile range; LDA, low disease activity; MTX, methotrexate; n, number of pts meeting assessment criteria; QD, once dailyConclusion:Although clinical/functional responses were generally similar between treatment groups, numerical improvements were seen for some efficacy endpoints with tofacitinib + MTX vs tofacitinib + PBO. A numerically higher CRFP rate may be associated with higher DAS28-4(ESR) disease activity. CRP changes up to W48 may not trend with CRFP status.References:[1]Cohen et al. Lancet Rheumatol 2019; 1: E23-34.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Anthony G McCluskey, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Stanley B. Cohen Consultant of: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Yi-Hsing Chen Grant/research support from: Bristol-Myers Squibb, GlaxoSmithKline, Pfizer Inc, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Tatjana Lukic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jerome Paulissen Consultant of: Pfizer Inc, Haiyun Fan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Tomohiro Hirose Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Edward Keystone Speakers bureau: AbbVie, Amgen, F. Hoffman-La Roche, Janssen, Merck, Novartis, Pfizer Inc, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Janssen, Merck, Myriad Autoimmune, Pfizer Inc, Sandoz, Sanofi Genzyme, Samsung Bioepsis, Grant/research support from: Amgen, Merck, Pfizer Inc, PuraPharm

Background: Tolerability remains ill-defined in clinical trials and commonly refers to non-serious adverse events (AEs) impacting patient (pt) satisfaction and treatment adherence. Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Objectives: This update to a previously published post hoc analysis1 describes the frequency and duration of the most common tolerability-related non-serious AEs in pts with RA receiving tofacitinib 5 mg BID as monotherapy or with conventional synthetic (cs)DMARDs in Phase (P)3 and P3b/4 studies. Methods: Data were pooled from: ORAL Step (NCT00960440); ORAL Solo (NCT00814307); ORAL Scan (NCT00847613); ORAL Sync (NCT00856544); ORAL Standard (NCT00853385); and ORAL Strategy (NCT02187055). This post hoc analysis included data from pts receiving tofacitinib 5 mg BID monotherapy (ORAL Solo, ORAL Strategy), placebo (PBO; ORAL Solo), or tofacitinib 5 mg BID or PBO with csDMARDs (all studies except ORAL Solo). Non-serious AEs (affecting pts’ day-to-day experience and ability to tolerate therapy) with incidence rates (IRs, pts with events/100 pt-years) ≥5 were evaluated up to Month (M)3. Infections, laboratory test abnormalities, general disorders or events not directly reported by pts, and musculoskeletal disorders likely due to underlying RA, were excluded. Results: Of the 2657 pts included in the analysis, 1976 received tofacitinib 5 mg BID (monotherapy: N=627; combination: N=1349) and 681 received PBO (monotherapy: N=122; combination: N=559). The most frequent non-serious AEs up to M3 are shown in the Table. IRs ≥10 were seen for headache and diarrhoea (tofacitinib 5 mg BID monotherapy, combination therapy and PBO monotherapy), and nausea (PBO monotherapy and PBO combination therapy). Non-serious AE duration was ≤4 weeks for most pts with headaches, diarrhoea or gastric discomfort (any gastrointestinal pain, dyspepsia, epigastric discomfort or abdominal discomfort/pain). With tofacitinib 5 mg BID and PBO, respectively, duration of AEs was ≤2 weeks for 43.2% and 64.7% of pts with headaches; 66.1% and 81.3% with diarrhoea; and 36.2% and 58.6% with gastric discomfort. Most non-serious AEs were mild/moderate. Conclusion: Overall, non-infectious non-serious AEs were mild/moderate and the majority were self-limiting. Non-serious AE frequency was similar for tofacitinib monotherapy and combination therapy, and for tofacitinib and PBO. References [1] Dikranian A, et al. Arthritis Rheumatol 2013; 65: S192. Acknowledgement: Study sponsored by Pfizer Inc. Medical writing support was provided by Anthony G McCluskey of CMC Connect and funded by Pfizer Inc. Disclosure of Interests: Ara Dikranian Consultant for: AbbVie, Pfizer Inc, Speakers bureau: AbbVie, Pfizer Inc, Jurgen Wollenhaupt Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, Valderilio F Azevedo Grant/research support from: AbbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer Inc, UCB, Consultant for: AbbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer Inc, UCB, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Celgene, Eli Lilly, Novartis, Pfizer Inc, David Gold Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrea Shapiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB

Background: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Previous analyses have reported greater improvements in efficacy outcomes with tofacitinib 5 mg twice daily (BID) conventional synthetic DMARDs (csDMARDs) in patients (pts) with early vs established RA.1,2 Objectives: To evaluate the efficacy and safety of tofacitinib in pts with RA, stratified by prior csDMARD treatment duration and number of prior csDMARDs. Methods: This was a post hoc analysis of pooled data from 4 Phase (P)3 trials (ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync [NCT00856544]; ORAL Standard [NCT00853385]) and 1 P3b/4 trial (ORAL Strategy [NCT02187055]) of tofacitinib in pts with RA and an inadequate response to =1 DMARD. Pts treated with tofacitinib 5 mg BID as monotherapy or with csDMARDs were included. Outcomes were evaluated according to csDMARD treatment duration (=1, 12, >2 years *y+) and number of csDMARDs (1, 2, 3, =4) prior to baseline (BL). Efficacy outcomes assessed at Months (M)3, 6 and 12 were: change from BL (?) in CDAI and HAQ-DI, and rates of CDAI-defined low disease activity (LDA; =10) and remission (=2.8). Safety outcomes, including treatment-emergent adverse events (AEs), serious AEs (SAEs) and AEs of special interest, were evaluated throughout the studies. Results: In total, 1584 pts were included in the analysis; of these, 27.2% (n=431) had received csDMARDs for =1 y, 20.5% (n=325) for 12 y, and 52.1% (n=825) for >2 y prior to BL (duration unknown for 3 pts). Roughly half (53.2%, n=842) had received 1 prior csDMARD; 26.4% (n=418), 13.8% (n=219) and 6.6% (n=105) had received 2, 3 and =4 prior csDMARDs, respectively. Most pts had previously received MTX (50.8%, n=805) or MTX + other csDMARDs (46.3%, n=733); 2.9% (n=46) received other csDMARDs only. Mean BL CDAI and HAQ-DI scores were similar, irrespective of prior csDMARD treatment duration or number of prior csDMARDs (Table). Generally, up to M12, no trends were observed for ?CDAI, ?HAQ-DI or CDAI LDA rates regardless of prior csDMARD treatment duration or number of prior csDMARDs (Table). When CDAI remission rates data were stratified by csDMARD treatment duration, no differences between pt groups were observed at M3 and M6; however, a numerically higher proportion of pts with prior csDMARD treatment duration =1 y achieved remission at M12 vs 12 y and >2 y pts. Use of fewer prior csDMARDs appeared to be associated with higher remission rates up to M12. Although safety outcomes were similar when data were stratified by prior csDMARD treatment duration, there was generally a trend for increased rates of AEs, SAEs and AEs of special interest (serious infections, herpes zoster and opportunistic infections [excluding TB]) with increasing number of prior csDMARDs (Table). Conclusion: In this post hoc analysis of pooled data from P3 and P3b/4 trials, no differences in the efficacy or safety of tofacitinib 5 mg BID were observed when pts were stratified by prior csDMARD treatment duration. Although pt numbers were small, use of fewer prior csDMARDs may be associated with improved remission rates and safety outcomes for pts treated with tofacitinib. References [1] Hall S et al. Arthritis Rheum 2016; 68 (S10): 1999-2001. [2] Fleischmann RM et al. RMD Open 2016; 2: e000262. Acknowledgement: Study sponsored by Pfizer Inc. Medical writing support was provided by Kirsten Woollcott of CMC Connect and funded by Pfizer Inc. Disclosure of Interests: Daniel Aletaha Grant/research support from: AbbVie, Bristol-Myers Squibb, and MSD, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Medac, Merck, MSD, Pfizer Inc, Roche, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Medac, Merck, MSD, Pfizer Inc, Roche, and UCB, Juan Jose Gomez-Reino Grant/research support from: Biogen, Gilead, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, Consultant for: Biogen, Gilead, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, Gerd Rdiger Burmester Consultant for: Roche, Sanofi-Genzyme, Speakers bureau: Roche, Sanofi-Genzyme, Ronald van Vollenhoven Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, GSK, Pfizer Inc, Roche and UCB, Consultant for: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, Eli Lilly, GSK, Janssen, Merck, Novartis, Pfizer Inc, Roche, UCB and Vertex, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Salim Benkhalifa Shareholder of: Pfizer SAS, Employee of: Pfizer SAS, Palle Dahl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). The impact of methotrexate (MTX) withdrawal in patients (pts) with RA who achieve low disease activity (LDA) or remission following treatment with tofacitinib in combination with MTX is unclear. Objectives To compare the efficacy and safety of tofacitinib modified-release (MR) 11 mg once daily (QD) with and without MTX in pts with RA who have achieved LDA with tofacitinib and MTX. Methods ORAL Shift (NCT02831855) was a global Phase 3b/4 study in pts aged ≥18 years with moderate to severe RA and an inadequate response to MTX. Pts received open-label (OL) tofacitinib MR 11 mg QD with MTX (tofacitinib + MTX) for 24 weeks. Pts achieving LDA (CDAI ≤10) at Week (W)24 entered the 24-week double-blind (DB) MTX withdrawal phase and were randomised 1:1 to receive tofacitinib MR 11 mg QD with placebo (tofacitinib monotherapy; ie underwent blinded MTX withdrawal) or continue tofacitinib + MTX. The primary endpoint was least squares mean change from W24 to W48 (Δ; DB phase) in DAS28 4(ESR). Non inferiority of tofacitinib monotherapy vs tofacitinib + MTX was declared if the upper bound of the 95% two-sided confidence interval (CI) for the difference in ΔDAS28-4(ESR) between arms was Results Of 694 pts in the OL phase, 530 achieved CDAI-defined LDA at W24 and were treated in the DB phase (tofacitinib monotherapy: n=264; tofacitinib + MTX: n=266). Demographics and pt characteristics at OL-phase baseline were similar between treatment arms. The difference (95% CI) between arms in ΔDAS28 4(ESR) (primary endpoint) was 0.30 (0.12, 0.48; Table 1) at W48, demonstrating that tofacitinib monotherapy was non-inferior to tofacitinib + MTX. Consistent with the primary endpoint, ΔDAS28-4(CRP)/SDAI/CDAI were greater for tofacitinib monotherapy vs tofacitinib + MTX, but these differences were not clinically meaningful; ACR/HAQ-DI response and LDA rates were generally similar between arms (Table). Remission rates were also similar between arms and generally did not change after MTX withdrawal. In the DB phase, rates of AEs, serious AEs, discontinuations due to AEs and AEs of special interest were generally comparable between arms (Table 1). Conclusion Pts receiving tofacitinib MR 11 mg QD + MTX who achieve LDA may withdraw MTX up to W48 without significant worsening of disease activity. Pts in remission tend to remain in remission after MTX withdrawal. Safety appeared consistent with the known profile of tofacitinib. Reference [1] Felson DT et al. Arthritis Rheum 2011;63:573-586 Acknowledgement Study sponsored by Pfizer Inc. Medical writing support was provided by C Viegelmann of CMC Connect and funded by Pfizer Inc. Disclosure of Interests Stanley B. Cohen Grant/research support from: AbbVie, Eli Lilly, Genentech, Gilead, Pfizer Inc, Consultant for: AbbVie, Eli Lilly, Genentech, Gilead, Pfizer Inc, Janet Pope Grant/research support from: Bristol-Myers Squibb, Roche, Seattle Genetics, UCB, Consultant for: AbbVie, Actelion, Amgen, Bayer, Bristol-Myers Squibb, Lilly, Merck, Novartis, Pfizer Inc, Roche, Sandoz, Sanofi, UCB, Boulos Haraoui Grant/research support from: AbbVie, Pfizer Inc, Consultant for: AbbVie, Amgen, Eli Lilly, Merck, Pfizer Inc, UCB, Fedra Irazoque-Palazuelos Consultant for: Bristol-Myers Squibb, Janssen, Pfizer Inc, Roche, UCB, Mariusz Korkosz Consultant for: AbbVie, Lilly, MSD, Novartis, Roche, UCB, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Tatjana Lukic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Shixue Liu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Noriko Iikuni Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Edward Keystone Grant/research support from: AbbVie, Amgen, Lilly Pharmaceuticals, Pfizer Inc, PuraPharm, Sanofi-Aventis, Consultant for: AbbVie, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Celltrion, Crescendo Bioscence, F. Hoffman-La Roche, Genentech, Gilead, Janssen, Lilly Pharmaceuticals, Merck, Pfizer Inc, Sandoz, Sanofi-Genzyme, Samsung Bioepis, UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb Canada, F. Hoffman-La Roche, Janssen, Merck, Pfizer Inc, Sanofi-Genzyme, UCB

Background: Tofacitinib is an oral JAK inhibitor for the treatment of RA. Pain is the most common symptom reported by patients (pts) with RA,1,2 thus reduction of pain is an important treatment goal. Objectives: To evaluate the effect of tofacitinib monotherapy ± pain medication on pain in pts with RA. Methods: This pooled post hoc analysis included pts who received tofacitinib 5 mg BID monotherapy (ie without csDMARDs) in Phase (P)2 (NCT00550446), P3 (ORAL Solo; NCT00814307) and P3b/4 (ORAL Strategy; NCT02187055) studies. Pts were stratified by concomitant use of ‘any pain therapy’ (opioids, plain analgesics [eg acetaminophen], NSAIDs or glucocorticoids [GC; ≤10 mg of prednisone or equivalent per day]), ‘pure analgesics’ (opioids or plain analgesics) and ‘adjuvant analgesics’ (NSAIDs or GC). Pts receiving pain medication at baseline (BL) maintained a stable dose during the studies; opioid and/or acetaminophen dose could be increased as rescue therapy. Efficacy outcomes were assessed at Month (M)3 and M6: change from BL (δ) in Pt Assessment of Pain (Pain; visual analogue scale [VAS]) and δPain stratified by DAS28-4(ESR)-defined low disease activity (LDA; ≤3.2) status at M3 and M6. Results: Of 676 pts who received tofacitinib 5 mg BID monotherapy, 604 (89%) received ‘any pain therapy’, 141 (21%) received ‘pure analgesics’ and 589 (87%) received ‘adjuvant analgesics’. Demographics and BL disease characteristics, including disease activity and Pain VAS, were generally similar when stratified by use/type of pain medication. Reductions in pain (δPain VAS) at M3 and M6 were generally similar for pts who received tofacitinib with ‘any pain therapy’ vs those who did not receive ‘any pain therapy’ (Figure 1a). There was a trend for a numerically greater reduction in pain at M3 and M6 in pts who received tofacitinib with ‘any pain therapy’ and who achieved LDA at M3 and M6 vs those who received tofacitinib with ‘any pain therapy’ and did not achieve LDA (95% CI overlapped; Figure 1b). By contrast, pain reductions were similar for pts who received tofacitinib without ‘any pain therapy’, irrespective of LDA status. Similar trends were seen when pts were stratified by use of ‘pure analgesics’ and ‘adjuvant analgesics’ (data not shown). Conclusion: In this pooled post hoc analysis, pain reduction was similar in pts with RA receiving tofacitinib, regardless of pain medication use. Pain reduction was similar in pts receiving tofacitinib without ‘any pain therapy’, irrespective of LDA status. These results should be interpreted with caution, as pain medication could be used as rescue therapy, few pts received tofacitinib without ‘any pain therapy’, and confounding by indication cannot be excluded. Further analyses are required to explore the impact of tofacitinib on the relationship between reductions in pain and disease activity. References [1] Walsh DA, McWilliams DF. Curr Pain Headache Rep 2012; 16: 509-17. [2] American College of Rheumatology Pain Management Task Force. Arthritis Care Res (Hoboken) 2010; 62: 590-9. Acknowledgement: Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc. Disclosure of Interests: Peter C. Taylor Grant/research support from: Celgene, Galapagos, Eli Lilly, UCB, Consultant for: AbbVie, Galapagos, Gilead, Eli Lilly, Pfizer Inc, Mart van de Laar Grant/research support from: AbbVie, Eli Lilly, Janssen-Cilag, Merck Inc, Pfizer Inc, Sanofi Genzyme, Speakers bureau: Eli Lilly, Pfizer Inc, Jeffrey R. Curtis Grant/research support from: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Consultant for: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Valderilio F Azevedo Grant/research support from: AbbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer Inc, UCB, Consultant for: AbbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer Inc, UCB, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Palle Dahl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Noriko Iikuni Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Salim Benkhalifa Shareholder of: Pfizer SAS, Employee of: Pfizer SAS, Juan Jose Gomez-Reino Grant/research support from: Biogen, Gilead, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, Consultant for: Biogen, Gilead, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, maxime dougados Grant/research support from: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Consultant for: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma

Background:ORAL Shift, a global Phase 3b/4 non-inferiority study, demonstrated sustained efficacy and safety of tofacitinib modified-release (MR) 11 mg once daily (QD) following methotrexate (MTX) withdrawal in patients with rheumatoid arthritis (RA) who achieved Clinical Disease Activity Index (CDAI) low disease activity (LDA) after treatment with tofacitinib + MTX.1Objectives:To assess predictors of durable clinical response in patients receiving tofacitinib MR 11 mg QD in ORAL Shift.Methods:ORAL Shift (NCT02831855) enrolled patients aged ≥18 years with moderate to severe RA and an inadequate response to MTX. Patients received open-label tofacitinib MR 11 mg QD + MTX for 24 weeks. Patients achieving LDA (CDAI score ≤10) at Week (W)24 entered the 24-week double-blind MTX withdrawal phase and were randomised 1:1 to receive tofacitinib MR 11 mg QD + placebo (tofacitinib monotherapy; ie blinded MTX withdrawal) or continue tofacitinib + MTX. In this post hoc analysis of randomised patients, we assessed predictors of durable response (maintenance of response from W24–48) per CDAI LDA and remission (CDAI score ≤2.8) criteria. All covariates were initially assessed for significance in a univariate logistic regression. Highly correlated covariates were reviewed to assess which would be removed prior to modelling in a multivariable logistic regression. Remaining significant (p≤0.10) covariates in the univariate regression were selected in the model using a stepwise selection process with p≤0.15 entry and p≤0.05 stay criteria. From the final model, estimated odds ratios (ORs) with 95% confidence intervals (CIs) are presented.Results:In the double-blind phase of ORAL Shift, durable CDAI LDA and remission rates were: 66.2% and 14.7%, respectively, with tofacitinib + MTX (N=266); and 55.3% and 11.0%, respectively, with tofacitinib + placebo (N=264) (Table 1). In the multivariable analysis, five patient covariates significantly predicted durable CDAI LDA (Figure 1; discussed hereafter). Each unit increase in CDAI score at W24 reduced the likelihood of maintaining CDAI LDA by 22.0%. Each unit increase in C-reactive protein (CRP) at W24 increased the likelihood of maintaining CDAI LDA by 4.0%; this may have been due to imbalanced CRP levels at W24 (randomisation) between treatment groups (Figure 1, footnote c). The odds of durable CDAI LDA were 53.0% lower in the US vs Europe and 61.0% lower in the US vs ‘other’ regions. Each unit increase in baseline Health Assessment Questionnaire-Disability Index (HAQ-DI) score reduced the odds of durable CDAI LDA by 34.0%. Patients receiving tofacitinib + MTX had 66.0% greater odds of durable CDAI LDA vs patients receiving tofacitinib + placebo. CDAI at W24 was the only significant predictor of durable CDAI remission in the multivariable analysis: OR (95% CI) 0.32 (0.24, 0.43); pTable 1.Durable CDAI LDA and remissiona in patients receiving tofacitinib MR 11 mg QD with MTX or placebo in the double-blind phase of ORAL ShiftTofacitinib + MTX(N=266)Tofacitinib + placebo(N=264)Durable CDAI LDA, n (%)176 (66.2)146 (55.3)Durable CDAI remission, n (%)39 (14.7)29 (11.0)aDurable CDAI LDA or remission was defined as achievement of LDA (CDAI score ≤10) or remission (CDAI score ≤2.8), respectively, at W24–48N, number of patients in each group; n, number of patients achieving outcomeConclusion:This post hoc analysis of data from ORAL Shift found that CDAI and CRP at W24, geographic region, baseline HAQ-DI and treatment could be predictors for durable CDAI LDA. As these findings were limited to patients who achieved CDAI LDA at W24 with tofacitinib MR 11 mg QD + MTX, additional data in the general patient population need to be investigated.References:[1]Cohen et al. Lancet Rheumatol 2019; 1: E23-34.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Kunihiro Yamaoka Speakers bureau: Actelion, Astellas, Chugai, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer Inc, Takeda, Consultant of: Actelion, Astellas, Chugai, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer Inc, Takeda, Stanley B. Cohen Consultant of: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Josef S. Smolen Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead Sciences, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, Grant/research support from: AbbVie and AstraZeneca

Background:A prior post hoc analysis of tofacitinib clinical trial data reported improvements in rheumatoid arthritis (RA) outcomes with tofacitinib vs placebo (PBO) through Month (M)6, regardless of baseline (BL) body mass index (BMI).1Objectives:To assess change from BL (Δ) in BMI, and disease activity by BL BMI status, in patients (pts) with moderate/severe RA receiving tofacitinib through M12.Methods:This post hoc analysis included data pooled from Phase 3 and 3b/4 studies of pts who were methotrexate-naïve (NCT01039688) or inadequate responders to conventional synthetic (cs) or biologic DMARDs (NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT02187055; NCT02831855). Pts received ≥1 dose of tofacitinib 5 or 10 mg twice daily (BID) or 11 mg once daily (QD), ± csDMARDs, or PBO. Least squares (LS) mean ΔBMI (linear mixed model repeated measures; observed cases) was summarised for all treatment groups at M3/6/12 (M3/6 only for tofacitinib 11 mg QD and PBO). Other assessments at M3/6/12 included ΔBMI ± BL concomitant glucocorticoids (GCs) or antidepressants (descriptive statistics), LS mean ΔDAS28-4(ESR) stratified by BL BMI status (Results:In total, 2349, 1611, 694 and 681 pts received tofacitinib 5 mg BID, 10 mg BID, 11 mg QD or PBO, respectively. Demographics/baseline characteristics were generally similar across treatments, except for some numerical differences in the tofacitinib 11 mg QD group, eg fewer female pts, more White pts and fewer pts receiving concomitant GCs, compared with other treatment groups. At M3/6, LS mean BMI significantly increased from BL with all tofacitinib doses vs PBO (all p30, for all tofacitinib doses. LS mean ΔDAS28-4(ESR) was generally greatest with tofacitinib 10 mg BID and 11 mg QD vs 5 mg BID across BL BMI status groups (Figure 1c). Across treatments, model-adjusted associations between LS mean ΔDAS28-4(ESR) and ΔBMI were weak (correlation coefficients all Table 1.Correlations between LS mean ΔDAS28-4(ESR) and ΔBMI through M12Tofacitinib5 mg BIDTofacitinib10 mg BIDTofacitinib11 mg QDPBONCorrelation coefficientNCorrelation coefficientNCorrelation coefficientNCorrelation coefficientM320210.116913480.12406410.09075540.0783M619180.130512700.13976110.04381500.1556M1214550.12138740.1826----Slopes for associations between LS mean ΔBMI and ΔDAS28-4(ESR) were significantly different from 0 at M3/6/12 with tofacitinib 5 and 10 mg BID (all pNCT02831855), only data to M6 were included. Pts who advanced from PBO to tofacitinib were not analysed post-advancementDAS28-4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; N, number of pts analysedConclusion:LS mean ΔBMI was greater with tofacitinib (all doses) vs PBO at M3/6, and with tofacitinib monotherapy vs combination therapy at M3/6/12. Improvements in DAS28-4(ESR) were seen across all BL BMI status groups. BMI increases with tofacitinib were only weakly associated with DAS28-4(ESR) improvements. The relationship between disease activity and ΔBMI requires further investigation.References:[1]Dikranian et al. Arthritis Rheumatol 2018; 69 (S10): Abs 2371.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Anthony G McCluskey, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Jürgen Wollenhaupt Speakers bureau: Pfizer Inc, Consultant of: Pfizer Inc, Jacques Morel Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Claire Daien Consultant of: Abivax, Grant/research support from: AbbVie, Bristol-Myers Squibb, Chugai, Eli Lilly, MSD, Novartis, Pfizer Inc, Sandoz, Adeline Ruyssen-Witrand Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Mylan, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Mylan, Pfizer Inc, Cédric Lukas Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer Inc, Sanofi Genzyme, UCB, Grant/research support from: Novartis, Pfizer Inc, Christophe Richez Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Mylan, Pfizer Inc, Grant/research support from: Biogen, Eli Lilly, Glenmark, Nordic Pharma, Roche, Andrea Shapiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Douglass Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Magali CROS Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gustavo Citera Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme

Imprinting theory suggests that founding conditions are ‘stamped’ on organizations, and these imprinted routines often resist change. In contrast, strategic choice theory suggests that the firm can overcome organizational inertia and deliberately choose its future. Both theories offer dramatically different explanations behind an organization's capacity for change. IPO firms provide a unique context for exploring how imprinting forces interact with strategic choice factors to address organizational capacity for change as a firm moves from private to public firm status. Juxtaposing imprinting and strategic choice perspectives, we employ fuzzy set analysis to examine the multi-level determinants of organizational capacity for change. Our cross-national data reveal three effective configurations of organizational capacity for change within IPOs, and two ineffective configurations. Our results suggest that the antecedents of organizational capacity for change in entrepreneurial threshold firms are non-linear, interdependent, and equifinal.

The theme of Redistributed Manufacturing (RdM) has gained in interest over recent years. While much research has taken place into the effects of RdM on current manufacturing models very few people have proposed new business models for this concept. The RdM studio is a new approach to business model development that will allow future users to dynamically incorporate data and experiment with new redistributed manufacturing scenarios. An RdM System Dynamics (SD) model is illustrated (as a potential constituent model of the RdM studio) with a case study called ShoeLab that explores RdM scenario generation through parameter sets utilising the SD modelling method. This research provides a valuable platform on which future models and scenarios may be derived.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Prior evidence suggests that board independence may enhance financial performance, but this relationship has been tested almost exclusively for Anglo-American countries. To explore the boundary conditions of this prominent governance mechanism, we examine the impact of the formal and information institutions of 18 national business systems on the board independence-financial performance relationship. Our results show that while the direct effect of independence is weak, national-level institutions significantly moderate the independence-performance relationship. Our findings suggest that the efficacy of board structures is likely to be contingent on the specific national context, but the type of legal system is insignificant.

Prior studies of IPO underpricing, mostly using agency theory and single-country samples, have generally fallen short. In this study, we employ the knowledge-based view (KBV) to explore underpricing across 17 countries. We find that agency indicators are insignificant predictors, board of director knowledge limits underpricing, and external knowledge both substitutes for and complements internal board knowledge. This third finding suggests that future KBV studies should consider how internal and external knowledge states interact with each other. Our study offers new insights into the antecedents of underpricing and extends our understanding of comparative governance and the KBV of the firm.

PurposeThe purpose of this paper is to test the relationship between board and top management team (TMT) members' international experience and CEO multinationality, with their firm's degree of internationalization. Through the lenses of upper echelon theory, on a sample of 108 European and US firms, the author tests the variables “international experience” and “CEO multinationality”, at the board and at the TMT levels.Design/methodology/approachA longitudinal research design is used to examine director's individual attributes in 2001 and firm's degree of internationalization in 2003‐2008. The sample comprised directors of the 108 largest European and US service and industrial firms by market capitalization, as listed in the Financial Times (FT) Global index of 2007.FindingsA positive effect is found on internationalization for international experience of both boards and TMTs; also a positive relationship is found between CEO multinationality of TMTs and internationalization.Research limitations/implicationsIt is acknowledged that the use of a diversified set of large US and European public firms could add unnecessary variance due to the different contexts involved in a sample of just 108 firms. Most of the sampled firms are already international so the study does not argue for board and TMT composition as a triggering mechanism for firm internationalization but, instead, as a tool that can enhance an international expansion process. The fact that international experience is a binary variable also limits the validity of the results. Either a direct survey of directors or a continuous variable that measures the amount in years of international experience would have yielded richer data. Data availability constraints limited the scope of this variable. The chosen operationalization just measures the presence and not the depth of executive's international experience. Additionally, it is acknowledge that just eliminating supervisory board members that represent unions/workers does not completely homogenize boards from the different countries in the sample.Practical implicationsPractitioners could use these findings to improve their selection and training processes of both top managers and board members.Originality/valueThe paper extends upper echelons theory to the board of directors. The comparison of boards and TMTs will facilitate the differentiation of corporate elites. It also introduces a new study variable: CEO multinationality and finally, it uses a mixed geographical sample of large European and US firms.

Using a mixed US and European sample where both the board and TMT units are analyzed at the same time, we test the variables age, tenure and functional background. We extend the information/decision making perspective ( Williams & O’Reilly, 1998 ) to both TMTs and boards by analyzing them as separate but related entities. In line with our hypotheses we find a positive effect on internationalization for functional background diversity of both boards and TMTs. Contrary to our expectations longer TMT tenure and younger board age also have a positive effect on internationalization.

Through the lens of resource-dependence theory, we use the boards of 108 US and European firms to test the following variables: percentage of women, outsiders, government experience, and international members on firm internationalization. We find that the percentage of females and international members both have a positive effect on firm international diversification. Contrary to our expectations, we find that it is the percentage of insiders – and not outsiders as hypothesized – that is related to internationalization.

We test the association among country-level institutions and the formation of corporate governance legitimacy. Results in our sample show that formal institutions quality, including regulatory and ...

Empirical evidence shows that board independence may positively affect IPO performance, but this relationship is almost only explored within Anglo-American countries. Following calls to narrow the ...