Respondent-Driven Sampling in Participatory Research Contexts : Participant-Driven Recruitment This article reports on the use of respondent-driven sampling -LRB- RDS -RRB- in participatory and community-based research . Participant-driven recruitment -LRB- PDR -RRB- retains all of the analytic capabilities of RDS while enhancing the role of respondents in framing research questions , instrument development , data interpretation , and other aspects of the research process . Merging the capabilities of RDS with participatory research methods , PDR creates new opportunities for engaging community members in research addressing social issues and in utilizing research findings within community contexts . This article outlines PDR 's synthesis of RDS and participatory research approaches , describes how PDR is implemented in community contexts , and provides two examples of the use of PDR , illustrating its process , potentials , and challenges . Introduction This article reports on the use of respondent-driven sampling -LRB- RDS -RRB- in participatory and community-based research . Participant-driven recruitment -LRB- PDR -RRB- 1 -- 3 retains the analytic capabilities of RDS -LRB- e.g. , use of data on personal network sizes and recruiting patterns to control for selection bias and generate population estimates , sampling weights , and standard errors estimates -RRB- while enhancing the role of respondents in framing research questions , instrument development , data interpretation , and other aspects of the research process . PDR integrates two distinct research approaches -- the practices , analytic methods , and capacity to generate a statistically valid sample associated with RDS and the disciplines and techniques of participatory research including community-based participatory research -LRB- CBPR -RRB- and participatory action research -LRB- PAR -RRB- . By merging RDS with participatory research methods , PDR fosters new opportunities for engaging community members in research addressing social issues and in utilizing research findings within community contexts . In particular , it presents opportunities to integrate rigorous participatory methods with rigorous quantitative data analysis . This article outlines PDR 's synthesis of RDS and participatory research approaches , describes how PDR is implemented in community contexts , and provides two examples of the use of PDR illustrating its process , potentials , and associated challenges . The emphasis of the article is on field methodology , rather than on RDS data analysis . Foundations of PDR PDR developed through the integration of RDS with participatory research techniques . Key elements of RDS that distinguish it from other forms of chain-referral sampling include direct contact between recruiter and recruit -LRB- in contrast to referrals mediated through the researcher -RRB- , presence of a pre-existing reciprocal relationship between the recruiter and recruit , documentation of recruitment patterns , regulation of the number of recruits per recruiter , and collection of data regarding participants ' personal network sizes .4 Early in the development of RDS , as a way to engage injection drug users and other hidden populations in HIV prevention studies , researchers noted that peer-to-peer recruiting often led to informal peer education , resulting in a mild intervention effect .5 This paved the way for the development of a number of peer-driven interventions6 and suggested that RDS held potential as a sampling method in participatory research on social issues . Participatory research projects have investigated international development issues ,7 organizational change ,8,9 community development and advocacy needs ,10 health care and community health promotion ,5,11,12 environmental health and urban design , and social issues affecting adolescent health and development .13 -- 17 Participatory research approaches developed , in part , as a response to conditions of exclusion , oppression , and marginalization18 and , in part , as a strategy for addressing and compensating for some limitations of traditional research methods , enhancing the validity and utilization of research findings . Participatory approaches such as action research and empowerment evaluation are now practiced and discussed theoretically across a wide range of disciplines , including public health .11,12,19 Participatory research often engages those who are the focus of policies and programs to study the issues and conditions that affect their lives . Participatory methods also are used to research conditions within organizations , identifying issues and facilitating the development of strategies for resolving them .8 These approaches seek to elicit diverse perspectives , often using multiple research methodologies , including methods that promote discussion , deliberation , the development of critical thinking , and the exploration of social circumstances related to research questions . Participatory research seeks to generate knowledge that can be used to prompt collective action and change ; its premise is that research should be useful to communities , organizations , programs and participants at the same time as contributing to the academic and disciplinary literatures .9 Often , participatory research approaches seek to involve marginalized people in determining research questions and methods and in interpreting and utilizing research findings . Participatory research draws on local knowledge and emphasizes the involvement of non-academics . In particular , it seeks to mobilize and build upon the expertise of those whose lives are directly affected by the research issue .10 Ideally , stakeholders in participatory research stand positioned to act upon the new knowledge they have collectively generated . Action may occur at individual , interpersonal , organizational , and policy levels .13 If participants and communities involved in the research have access to data and findings , this may enable more nuanced data interpretation as well as higher commitment to utilizing results and to exploring emergent research questions . Research efforts that are viewed as sensitive to community concerns , locally engaged and sustained rather than extractive , may be better received by community members and potential respondents .11,20 Participatory research efforts often unfold over a relatively long period , and community-based participatory researchers have articulated crucial elements and stages that characterize effective collaborations .11 Participatory research faces a number of specific challenges : Careful negotiation of power dynamics between academic researchers and community members , as well as among community stakeholders , is crucial . Communication among partners is key and can be problematic -LRB- e.g. , academic researchers may be ill-equipped to readily understand community concerns and priorities ; community members may not readily endorse academic concerns about statistically valid samples -RRB- . The creation of a `` common language '' and common standards of practice , including standards for sampling and data integrity , by the research team is a long , iterative , demanding process . The synthesis of RDS with participatory research approaches contributes to resolving some of these challenges , in particular by providing a rigorous sampling technique that can present participatory researchers with a means to develop statistically credible samples without diminishing the quality of community engagement . RDS produces more reliable data than convenience or snowball samples through the use of data on personal network sizes and recruiting patterns to control for bias . In some cases , it generates more comprehensive data than either venue or institutional samples .21 Because RDS utilizes social networks and gives participants a central role in recruiting , it is more consistent with the values of participatory research than random sampling . Further , the involvement of participants in the sampling process opens up opportunities for dialogue and education regarding issues like data integrity , informed consent , and the overall aims of the research . At first conceived as a sampling methodology , RDS worked to engage disenfranchised and stigmatized people in HIV prevention studies , giving them a central role in recruiting and building upon their capabilities and strengths .6 Nonetheless , the initial studies using RDS were not explicitly framed as participatory research efforts . We propose PDR as a careful synthesis of the two approaches . PDR provides a context for RDS that is specifically adapted to the framework and demands of participatory research , while at the same time maintaining the core elements of RDS . Description of PDR As in other participatory research approaches , studies using PDR may be initiated by either researchers or community stakeholders or may develop out of an on-going collaboration . In any of these cases , PDR involves a number of stages , shown in Figure 1 , that situate the peer recruiting effort within a participatory research process that seeks to ensure both the relevance of the research aims to community stakeholders and the utilization of research findings . Figure 1Stages of a participatory research process utilizing PDR Community Engagement , Referral of `` Seeds '' and Pilot Activities In most participatory research projects , researchers collaborate with informal and formal stakeholder organizations to set and refine the research questions and aims . In PDR , these organizations also identify a limited number of potential study participants with diverse perspectives21 to pilot , review , and assist in the revision and adaptation of research materials and questionnaires and to serve as `` seeds '' -LRB- the foundation of the peer recruitment process -RRB- . The seeds in PDR have a pivotal role in the research process , involving several responsibilities and opportunities for engagement in addition to their roles as respondents and peer recruiters in RDS . Seeds take part in pilot groups to discuss the aims of the study and to assess and fine-tune research instruments , in some cases substantially co-designing the instruments in close collaboration with academic researchers . The involvement of community members in the design and development of research projects has multiple benefits and challenges that have been well articulated in the community-based participatory research literature .20 Engaging seeds in discussions regarding the design and implementation of the study enhances their familiarity with the research process and contributes to the incremental development of a `` common language '' by diverse members of the research team . Increasing the commitment of seeds to the overall research project assists in addressing challenges regarding recruiting rates and productivity of seeds encountered in some RDS studies : 22 The engagement and sense of ownership of the research by the seeds appears to lead to higher commitment to and capacity for peer recruitment and aids in developing recruiting momentum . It also helps to address challenges faced by participatory researchers : Peer recruitment enhances the level of engagement of participants in the overall research process by creating new opportunities for formal and informal dialogue about the research issues . Peer Recruitment After the pilot process has been completed , seeds recruit the first wave of participants , and peer recruitment continues through at least the number of waves required to obtain equilibrium .23 The recruiting process is generally similar to that in most studies using RDS , with the following differences : In most RDS studies , peer recruiters receive coupons with serial numbers and contact information for the research project , which they distribute to their recruits . In PDR , peer recruiters also receive written explanations of the research project , informed consent materials , and , in some cases , survey instruments and self-addressed stamped envelopes to convey to their recruits . In PDR studies that include group discussion or educational sessions , participants may have opportunities to discuss and/or role-play recruiting techniques . Incentives Participants receive small incentives for taking part in the study -LRB- e.g. , $ 15 for survey completion -RRB- and for recruiting their peers -LRB- e.g. , $ 10 for successfully recruiting an eligible participant -RRB- . In addition to these extrinsic incentives , engagement with the overall development of the research project and the interpretation and utilization of findings may serve as an additional incentive , fostering intrinsic interest and motivation among participants . Evaluations of PDR indicate that , while the availability of extrinsic incentives initially attracted participants , they stayed engaged based on intrinsic motivation , the quality of participation , opportunities to discuss important issues with peers , or interest in the questions addressed by the research . In the words of one adolescent participant : At the beginning , I wanted the money , but now it 's turned into something totally different ... . It surprises me -- so much has changed . I 've been able to meet people that I know I would n't have met -LSB- otherwise -RSB- . I 've been able to expand and learn , you know , get more involved in things that I like to do and hope to do in the future .2 Location Most RDS studies have a research office or storefront location where recruits meet individually with research staff to assess their eligibility , complete informed consent documents , be interviewed , and , in some cases , receive an educational session . In PDR , self-administered surveys and educational or discussion sessions may take place in a wide range of community settings identified as accessible during the pilot process . While this may reduce costs associated with space rental and help to reduce the `` geographic filtering '' 24 of RDS samples , it demands extra care in terms of participant confidentiality and data integrity -LRB- see below -RRB- . Data Interpretation and Utilization PDR participants are invited to attend periodic updates on the research and data interpretation meetings . As preliminary findings are developed , community stakeholders as well as participants take part in further data interpretation meetings , discussion regarding the study 's results , and activities leading to the dissemination and utilization of findings . Confidentiality and Management of Data Regarding Recruiting Patterns Because PDR research is relatively decentralized , special care is taken to explain informed consent , confidentiality , and other human subjects considerations to participants and to recruiters ; participants and other community members who are highly engaged in the research complete the same human subjects tutorial required of academic researchers . Participant referrals provide a tangible link between participants and their recruiters ; participants describe their relationship with the person who recruited them in order to ensure that it is reciprocal .21 Contact forms facilitate follow-up and payment of incentives . Personally identifying information is kept separately from research data sets , which include unique identifiers for recruiters and recruits ; all data is stored in secure locations at the university . Examples Two studies conducted by research teams including the author illustrate the process and challenges of implementing PDR . The first involved dislocated workers in a study of social protections and employment trajectories ; the second involved adolescents in community-based HIV prevention research . Instruments and procedures for both studies were approved by the Cornell University Committee on Human Subjects . Findings from both studies have been reported elsewhere2 ,3,25 -- 30 ; the emphasis here is on the field methodology . The aims of the studies and the rationale for utilizing PDR in each of them are briefly summarized below . A chart comparing the use of PDR in the two studies is presented in Table 1 . Table 1Comparison of the use of PDR in two studies Plant closure studyRural adolescent HIV prevention studyEngagementCommunity organizations involved in framing research and in recruiting seedsWorkforce Improvement Board , Workers Rights Council , YWCAYouth Bureau , Catholic Charities , Aid to Victims of Violence , Jacobus Center -LRB- reproductive health clinic -RRB- , YWCANumber of seeds involved in pilot process79Peer recruitmentDurationSummer 2000 -- spring 2001Winter 2001 -- spring 2002Projected sample size50125Actual sample size72128Number of waves57Distributed informed consent materialsYes -LRB- informed consent only -RRB- Yes -LRB- parental consent as well as informed consent/assent -RRB- IncentivesFor completing survey $ 15 $ 15For recruiting new participant $ 10 $ 10Steering incentives $ 20 -LRB- for recruiting dislocated workers who had held part-time or contingent positions ; for recruiting dislocated workers who had moved out of state to seek jobs -RRB- NoneLocationsWorkforce Improvement Board , Workers Rights Council , restaurants , private residences ; data interpretation sessions held in meeting rooms at Fire Hall and YWCAYouth Bureau , YWCA , Rural Services meeting room , classrooms in rural schoolLocation sensitivityNone -LRB- surveys could be self-administered and mailed in ; 11 % of participants were living out-of-state at the time of the survey -RRB- Significant -LRB- in rural areas close to survey sites , participant pool was saturated , while rural areas distant from survey sites were under-represented -RRB- Data interpretationFormal meetings with participants to review preliminary dataYesYesFormal meetings with stakeholder organizations to review findingsYes -LRB- separate meetings with each agency -RRB- Yes -LRB- group presentation and meetings on-site with some agencies -RRB- Written report to participantsYesNoLocal media coverageYes -LRB- researcher , agencies and participants -RRB- NoPresentations and publications outside the local communityYes -LRB- researcher only -RRB- Yes -LRB- co-authored with participants -RRB- Individual or organizational actions taken by participants attributed to involvement in researchYesYes Dislocated Workers PDR was developed in response to challenges encountered during a plant closure study conducted during 2000 -- 2001 . A non-unionized manufacturing plant employing nearly 500 people was shut down in early 1998 as a consequence of corporate restructuring . The plant had been the beneficiary of a variety of local economic development assistance packages in a community that had experienced the closure and downsizing of many other manufacturing firms . The study aimed to engage approximately 50 former workers in an extensive survey about their post-closure employment trajectories in order to inform ongoing social protection , planning and economic development efforts and to serve as a corrective to studies of the local impacts of the plant closure that neglected to gather data regarding dislocated workers .31 The former employees were in effect a hidden population ; no comprehensive list could be obtained to serve as a sampling frame although human resource records provided precise aggregate demographic information on the displaced workers . Further , a proportion of the workers had moved out of state after the closure , either relocating to other plants owned by the original firm or traveling in search of employment opportunities . Peer recruitment exceeded the original participation objective , engaging 72 dislocated workers in the study . PDR had the capacity to build upon the social connections among former workers to locate study respondents while simultaneously providing a context for the participants to explore , reflect upon , and deliberate about economic development strategies , employment trajectories , and measures of job quality . RDS analysis of the data aided in estimating post-closure out-migration rates . By combining RDS and participatory research methods , the study enabled an economically vulnerable population to contribute to the development of recommendations regarding community social protection and economic development programs . Rural Adolescents The second illustration of PDR is drawn from an HIV prevention study of rural adolescents . Peer recruitment slightly exceeded the original sampling objective -LRB- 128 youth participated ; the study enrollment goal was 125 -RRB- . Although many approaches may be taken to sampling adolescents , peer recruiting produces empirical data about social networks that can not be gathered in institutional or venue samples21 ; our study engaged homeless and out-of-school youth as well as youth enrolled in all local schools . RDS enables study of adolescents ' social networks -- in particular , the relationship of risk and protective characteristics and behaviors to social networks . With empirical evidence of recruiting patterns , both demographic and non-demographic characteristics can be mapped in relation to recruiting networks . This enabled us to explore the roles that risk and protective characteristics play in the social network structures of adolescents .32,33 Further , RDS analysis contributes to identifying sub-groupings of adolescents , work that is crucial to the development of effective tailored interventions .34 PDR enabled not only the gathering of data on recruiting patterns needed for RDS analysis but also engaged youth in a participatory learning process that was particularly appropriate to their developmental needs .2,30,33 Challenges and Lessons Learned There are a number of challenges involved in implementing PDR , these include fully utilizing RDS analysis during data interpretation sessions , addressing location sensitivity so that sampling is not distorted by lack of access to study sites , and preventing the emergence of `` super recruiters '' without dampening participants ' engagement in the overall study . RDS Analysis Both of the examples reported drew on early versions of RDS analysis software . This aided in identifying and addressing specific issues -LRB- e.g. , the relative disengagement of contingent workers from permanent employees ' social networks , the strong tendency of rural youth to recruit other rural youth -RRB- . RDS analysis requires significant data set preparation before data can be imported and used with the current specialized software package -LRB- Respondent Driven Sampling Analysis Tool -LRB- RDSAT -RRB- can be downloaded at no cost from http://www.respondentdrivensampling.org -RRB- . In the two studies cited , detailed RDS analyses were completed after recruitment ended and after most community-based discussions of the research had taken place . Deliberate procedures for incorporating RDS analyses into early data interpretation efforts are needed in order for community-based partnerships to benefit fully from the use of this sampling method .35 Location Sensitivity The participatory processes that are well integrated into PDR may assist in addressing the location sensitivity and `` geographic filtering '' 24 of RDS-based samples . Useful practices include soliciting guidance from study participants on accessible times , locations , and methods of survey administration . For example , surveys can be administered in community locations recommended by participants as accessible sites rather than at a centrally located research office or storefront . Pilot studies may suggest a protocol in which respondents are provided with self-administered questionnaires and informed consent materials to give or mail to other potential participants , facilitating engagement of participants who might otherwise be missed by the study -LRB- e.g. , dislocated workers who moved out of state after a plant closure -RRB- . `` Super Recruiters '' Regulating the number of participants that can be recruited by any one peer is a core element of RDS , generally accomplished by setting recruiting quotas and limiting the amount of recruiting materials -LRB- e.g. , coupons -RRB- offered to each participant . In many studies , highly committed participants emerge who are eager to promote the study and to recruit more new participants than their quota allows . In PDR , potential `` super recruiters '' can be engaged in elements of the participatory study other than recruiting , such as organizing data interpretation sessions or disseminating research findings within the community . Conclusions PDR relies on the careful implementation of the core elements of RDS . Additional defining elements of PDR include recruitment of diverse seeds through formal or informal stakeholder organizations , involvement of seeds in piloting and co-designing study instruments and procedures , human subjects education for community research partners , involvement of participants and stakeholders in data interpretation sessions , and dissemination of findings to inform local actions . Some of these elements are specific to PDR ; some are more general attributes of participatory or empowerment approaches .36 PDR seeks to enable eligible participants to make informed judgments about their own level of engagement in the study of potentially sensitive social issues . PDR creates formal and informal contexts for civic discussion that are accessible to research participants who might not attend community meetings or utilize other traditional means of voicing their experiences and views . It creates a socially embedded research process in which discussion of the research questions may take place when peers meet informally -LRB- e.g. , while shopping -RRB- as well as during formal data interpretation sessions . Being recruited by peers to take part in a research project serves for some as a bridge to civic engagement and fosters intrinsic interest in the questions and issues explored by the study . Thus , this approach to recruiting members of hidden , vulnerable , and marginalized populations to participate in research projects can contribute to more inclusive community dialogue about social issues and strengthen community participation in research efforts .

O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O B I O O O O O B I O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

participant-driven recruitment
respondent-driven sampling
community-based participatory research


Retrospective

clinical

study

on

the

notable

efficacy

and

related

factors

of

infliximab

therapy

in

a

rheumatoid

arthritis

management

group

in

Japan

one-year

clinical

outcomes

-LRB-

-RRB-

Biologics

targeting

TNF

have

brought

about

a

paradigm

shift

in

the

treatment

of

rheumatoid

arthritis

-LRB-

RA

-RRB-

and

infliximab

anti-TNF-α

chimeric

monoclonal

antibody

was

marketed

in

in

Japan

We

previously

reported

on

the

RECONFIRM

study

a

retrospective

clinical

study

on

the

efficacy

of

infliximab

therapy

in

a

RA

management

group

in

Japan

where

we

evaluated

the

clinical

response

after

weeks

of

the

therapy

in

patients

The

study

reported

here

was

aimed

at

reconfirming

the

clinical

efficacy

of

the

infliximab

therapy

and

demographic

factors

related

to

the

efficacy

over

a

study

period

in

RA

patients

in

the

same

study

group

Infliximab

was

infused

according

to

the

domestically

approved

method

and

the

clinical

response

was

evaluated

following

weeks

of

infliximab

therapy

using

the

European

League

Against

Rheumatism

-LRB-

EULAR

-RRB-

response

criteria

Disease

activity

was

assessed

by

-LRB-

Disease

Activity

Score

including

a

count/C-reactive

protein

-RRB-

Infliximab

was

discontinued

in

of

the

patients

at

weeks

and

and

discontinued

the

therapy

due

to

adverse

events

and

inefficiency

respectively

Average

decreased

from

at

week

to

at

week

after

the

therapy

Patients

in

remission

and

those

showing

low

moderate

and

high-disease

activity

changed

from

and

respectively

at

the

start

of

the

study

to

and

respectively

at

week

Younger

age

RF-negativity

and

low

scores

of

showed

significant

correlations

with

remission

at

week

EULAR

response

criteria

good

moderate

and

no

response

to

infliximab

were

and

respectively

In

conclusion

we

reconfirmed

the

clinical

efficacy

of

infliximab

and

demographic

factors

related

to

the

efficacy

over

a

study

period

in

Japanese

patients

with

RA

using

and

EULAR

response

criteria

Introduction

Rheumatoid

arthritis

-LRB-

RA

-RRB-

is

a

chronic

systemic

inflammatory

disease

that

causes

significant

morbidity

and

mortality

RA

patients

should

be

started

with

DMARDs

as

early

as

possible

and

among

multiple

DMARDs

methotrexate

-LRB-

MTX

-RRB-

is

considered

the

anchor

drug

and

should

be

used

first

of

all

However

even

the

use

of

MTX

often

fails

to

control

disease

activity

and

to

prevent

structural

damage

and

so

more

effective

treatment

strategies

are

needed

TNF-α

plays

a

pivotal

role

in

the

pathological

processes

of

RA

through

the

accumulation

of

inflammatory

cells

and

the

self-perpetuation

of

inflammation

leading

to

cartilage

and

bone

destruction

The

combinational

use

of

biologics

targeting

TNF-α

and

MTX

has

revolutionized

the

treatment

of

RA

producing

significant

improvements

in

clinical

radiographic

and

functional

outcomes

that

were

not

previously

observed

-LSB-

-RSB-

Infliximab

anti-TNF-α

chimeric

monoclonal

antibody

has

been

marketed

since

July

in

Japan

and

currently

provides

high

efficacy

and

potential

adverse

events

Although

global

evidence

of

the

efficacy

and

safety

of

infliximab

has

accumulated

including

the

ATTRACT

study

ASPIRE

study

and

many

others

-LSB-

-RSB-

there

is

no

well-established

firm

evidence

of

the

efficacy

of

this

agent

in

Japan

Only

the

RECONFIRM

study

a

retrospective

clinical

study

on

the

notable

efficacy

and

related

factors

of

infliximab

therapy

in

a

RA

management

group

in

Japan

has

reported

clinical

evidence

on

its

efficacy

and

safety

this

study

was

performed

in

several

major

rheumatology

centers

in

Japan

-LSB-

-RSB-

However

the

RECONFIRM

study

evaluated

the

clinical

response

following

only

weeks

of

infliximab

therapy

in

patients

In

this

study

we

assessed

the

clinical

efficacy

and

safety

of

infliximab

and

MTX

over

a

study

period

when

used

in

RA

patients

in

the

same

group

in

order

to

reconfirm

not

only

its

clinical

efficacy

but

also

demographic

factors

related

to

the

efficacy

Patients

and

methods

Data

and

information

on

RA

patients

that

fulfilled

the

diagnostic

criteria

of

the

American

College

of

Rheumatology

-LRB-

ACR

-RRB-

were

collected

from

three

major

rheumatology

centers

in

Japan

including

the

First

Department

of

Internal

Medicine

School

of

Medicine

University

of

Occupational

and

Environmental

Health

Japan

Kitakyushu

the

Division

of

Rheumatology

and

Clinical

Immunology

Department

of

Internal

Medicine

Saitama

Medical

Center

Saitama

Medical

University

Saitama

and

the

Institute

of

Rheumatology

Tokyo

Women

's

Medical

University

All

patients

that

received

infliximab

treatment

in

each

institution

by

December

were

registered

with

this

retrospective

study

Demographic

data

including

disease

duration

and

concomitant

therapy

were

collected

from

medical

charts

The

following

parameters

were

evaluated

before

and

at

weeks

after

the

initial

infliximab

infusion

tender

joint

count

-LRB-

TJC

-RRB-

swollen

joint

count

-LRB-

SJC

-RRB-

patient

's

assessment

of

pain

on

a

visual

analog

scale

-LRB-

patient

's

pain

VAS

-RRB-

patient

's

global

assessment

of

disease

activity

-LRB-

patient

's

global

VAS

-RRB-

physician

's

global

assessment

of

disease

activity

-LRB-

physician

's

global

VAS

-RRB-

and

C-reactive

protein

-LRB-

CRP

-RRB-

Infliximab

therapy

Infliximab

was

infused

to

patients

at

zero

two

and

six

weeks

and

thereafter

every

eight

weeks

at

a

dose

of

mg/kg

according

to

the

drug

labeling

and

the

guidelines

of

the

Infliximab

Study

Group

in

the

Ministry

of

Health

Welfare

and

Labor

in

Japan

-LSB-

-RSB-

Concomitant

use

of

MTX

was

instituted

in

all

cases

although

the

dose

of

MTX

was

determined

by

each

attending

physician

Therapeutic

response

Disease

activity

was

assessed

by

Disease

Activity

Score

including

a

count

-LRB-

-RRB-

CRP

that

was

calculated

according

to

the

authorized

formula

-LRB-

-RRB-

The

value

of

is

reported

to

be

less

than

the

original

using

the

erythrocyte

sedimentation

rate

-LRB-

ESR

-RRB-

and

we

used

a

threshold

of

instead

of

the

original

as

the

cut-off

for

high

activity

and

instead

of

as

the

cut-off

for

low

activity

Thus

we

defined

a

value

of

as

high

activity

as

moderate

activity

as

low

activity

with

being

defined

as

remission

-LSB-

-RSB-

The

response

to

infliximab

therapy

at

weeks

was

evaluated

by

the

European

League

Against

Arthritis

-LRB-

EULAR

-RRB-

response

criteria

using

and

as

the

thresholds

for

the

high

and

low

disease

activities

respectively

-LSB-

-RSB-

Secondary

insufficiency

to

infliximab

was

defined

as

patients

with

good

or

moderate

EULAR

response

at

week

and

whose

increased

to

or

from

week

to

Discontinued

subjects

The

continuation

rate

of

infliximab

therapy

was

calculated

by

all

causes

of

discontinuation

Cumulative

hazards

and

associated

factors

were

analyzed

in

relation

to

three

types

of

discontinuation

adverse

events

inefficacy

and

remission

Statistical

analysis

Baseline

characteristics

of

patients

are

summarized

in

Table

using

the

mean

standard

deviation

median

and

values

for

continuous

variables

The

continuation

rate

of

infliximab

therapy

was

calculated

using

the

Kaplan

Meier

estimator

in

pooled

samples

of

three

institutes

The

discontinuation-cause

specific

hazards

were

estimated

using

the

Nelson

Aalen

estimator

Next

risk

factors

for

the

discontinuations

were

evaluated

using

the

stratified

proportional

hazards

model

in

order

to

adjust

for

differences

among

institutions

The

clinical

efficacies

of

infliximab

were

evaluated

using

a

multivariate

logistic

regression

to

adjust

for

institutional

effects

In

this

analysis

the

last

observed

values

were

used

for

discontinued

patients

All

multivariate

analyses

were

conducted

using

the

variables

gender

age

duration

of

disease

positive/negative

rheumatoid

factor

-LRB-

RF

-RRB-

concomitant

MTX

dose

concomitant

prednisolone

-LRB-

PSL

-RRB-

dose

and

at

baseline

All

reported

P-values

are

two-sided

and

are

not

adjusted

for

multiple

testing

The

significance

level

was

set

at

a

P

value

of

Table

characteristics

of

patients

in

three

institutions

of

rheumatology

in

MaxFemale

-LRB-

-RRB-

RF

positive

-LRB-

-RRB-

RF

-LRB-

titer

-RRB-

PSL

dose3.83.7004522.5CRP3.32.801.182.74.713.7TJC2810.57.30591528SJC2810.66.106101428GH63.121.9049.36680100DAS28-CRP5.51

MTX

methotrexate

PSL

prednisolone

RF

rheumatoid

factor

CRP

C-reactive

protein

GH

general

health

TJC

tender

joint

count

SJC

swollen

joint

count

DAS

disease

activity

score

Results

Baseline

demographic

and

clinical

characteristics

The

baseline

demographic

and

clinical

characteristics

of

patients

receiving

infliximab

therapy

are

summarized

in

Table

Patients

had

active

disease

at

baseline

as

evidenced

by

high

mean

counts

of

tender

and

swollen

joints

CRP

levels

and

the

Age

sex

and

disease

duration

were

similar

among

these

three

institutes

while

the

user

and

dose

of

MTX

or

PSL

were

divergent

and

the

disease

activities

as

assessed

by

TJC

SJC

GH

and

was

also

different

Continuation

of

infliximab

therapy

Infliximab

was

discontinued

in

cases

-LRB-

-RRB-

among

patients

during

a

period

and

the

survival

rate

for

infliximab

use

was

comparable

among

three

institutes

by

week

after

the

treatment

according

to

Kaplan

Meier

analysis

-LRB-

Fig.

-RRB-

Cumulative

hazards

of

the

discontinuation

during

the

infliximab

therapy

were

different

among

the

causes

of

discontinuation

discontinuation

due

to

adverse

events

inefficiency

remission

and

other

causes

-LRB-

such

as

change

of

hospitals/clinics

and

economic

reasons

-RRB-

were

and

respectively

-LRB-

Fig.

-RRB-

Although

the

cause

of

the

discontinuation

was

similar

among

three

institutes

adverse

events

were

higher

in

Center

than

in

the

other

two

institutes

and

remission

and

other

causes

including

economic

problems

of

the

patient

were

greater

in

Center

than

in

the

other

two

-LRB-

data

not

shown

-RRB-

In

patients

who

terminated

infliximab

treatment

stratified

Cox

regression

was

performed

to

analyze

factors

associated

with

the

discontinuation

of

the

infusion

Male

older

age

and

RF-negativity

were

significantly

associated

with

the

discontinuation

of

infliximab

due

to

adverse

reactions

whereas

there

was

no

significant

factor

responsible

for

the

discontinuation

due

to

maintained

remission

or

a

lack

of

efficacy

-LRB-

Table

-RRB-

Fig.

of

the

infliximab

therapy

in

RA

patients

for

weeks

a

Survival

rate

of

RA

patients

treated

with

infliximab

-LRB-

n

total

and

three

institutes

-RRB-

during

the

therapy

b

Cumulative

hazards

of

the

discontinuation

of

infliximab

therapy

by

week

of

the

treatmentTable

from

a

Cox

regression

analysis

performed

to

examine

the

factors

related

to

the

discontinuation

of

infliximab

therapyVariableAE

-LRB-

n

-RRB-

Inefficacy

-LRB-

n

-RRB-

Remission

-LRB-

n

-RRB-

Coef.HRCLCUPCoef.HRCLCUPCoef.HRCLCUPAge0

Gender

0.9400.3910.1770.8630.0200.1601.1730.3523.9100.79

RA

.0181.0180.9831.0540.3200.0051.0050.9641.0460.83

RF

-LRB-

-RRB-

0.9490.3870.1710.8780.0231.5454.6860.63534.5730.13

MTX

0.1420.8670.7091.0600.160.3391.4030.7992.4650.24

PSL

dose

0.0660.9360.8481.0330.1900.0031.0030.9081.1090.95

DAS

-LRB-

week

-RRB-

0.2051.2270.8901.6920.2100.1131.1200.8151.5370.49

Coef

coefficient

HR

hazard

ratio

CL

confidence

lower

limit

of

HR

CU

confidence

upper

limit

of

HR

Efficacy

of

infliximab

therapy

The

average

before

starting

infliximab

was

and

this

decreased

to

at

weeks

and

respectively

after

the

infliximab

therapy

-LRB-

Fig.

-RRB-

Disease

characteristics

at

baseline

and

after

and

weeks

of

the

inflilximab

therapy

were

as

follows

tender

joints

count

-LRB-

and

-RRB-

swollen

joints

count

-LRB-

and

-RRB-

GH

-LRB-

and

mm

-RRB-

and

CRP

-LRB-

and

mg/dl

-RRB-

-LRB-

Fig.

-RRB-

Before

starting

infliximab

the

proportions

of

patients

showing

low

moderate

and

high

disease

activity

were

and

respectively

At

week

patients

in

remission

-LRB-

defined

as

-RRB-

and

those

showing

low

-LRB-

-RRB-

moderate

-LRB-

-RRB-

and

high

disease

activity

-LRB-

-RRB-

had

changed

to

and

respectively

and

at

week

patients

in

remission

and

those

showing

low

moderate

and

high

disease

activity

were

and

respectively

-LRB-

Fig.

-RRB-

Thus

approximately

of

the

patients

satisfied

the

remission

criteria

at

week

and

still

remained

at

week

after

the

infliximab

therapy

Also

when

the

responses

were

evaluated

by

the

EULAR

response

criteria

the

proportions

for

good

moderate

and

no

response

to

infliximab

as

measured

by

were

and

respectively

at

week

and

and

respectively

at

week

-LRB-

Fig.

-RRB-

Fig.

analysis

of

values

during

the

study

of

patients

using

infliximab

Line

in

the

box

represents

the

median

and

the

upper

and

lower

ends

of

the

box

show

the

and

percentiles

of

the

populationFig

analysis

of

a

b

c

CRP

and

d

GH

values

during

the

study

of

patients

using

infliximab

Line

in

the

box

represents

the

median

and

the

upper

and

lower

ends

of

the

box

show

the

and

percentiles

of

the

populationFig

in

values

during

the

study

of

patients

using

infliximab

The

ratios

of

patients

who

demonstrated

high

disease

activity

-LRB-

defined

as

-RRB-

moderate

activity

-LRB-

-RRB-

low

activity

-LRB-

-RRB-

and

remission

-LRB-

-RRB-

at

each

observation

point

during

the

study

are

shownFig

response

to

infliximab

therapy

during

the

study

The

ratios

of

patients

whose

responses

were

evaluated

by

the

European

League

Against

Arthritis

-LRB-

EULAR

-RRB-

response

criteria

are

shown

Demographic

factors

related

to

the

clinical

efficacy

of

infliximab

therapy

In

order

to

clarify

demographic

factors

related

to

the

clinical

efficacy

of

infliximab

therapy

we

performed

a

multivariate

analysis

adjust

for

institutional

differences

Younger

age

RF-negativity

and

lower

levels

of

were

significantly

associated

with

the

clinical

remission

induced

by

infliximab

therapy

at

week

whereas

gender

duration

of

the

disease

dose

of

MTX

and

dose

of

PSL

did

not

show

a

significant

association

-LRB-

Table

-RRB-

On

the

other

hand

most

of

the

demographic

factors

except

for

older

age

did

not

affect

secondary

insufficiency

from

week

to

after

the

infliximab

therapy

according

to

the

logistic

regression

analysis

-LRB-

Table

-RRB-

Table

from

the

logistic

regression

analysis

used

to

examine

the

factors

related

to

clinical

remission

at

weeks

and

induced

by

infliximab

therapyVariablesWeek

-LRB-

n

-RRB-

Week

-LRB-

n

-RRB-

.5304.6171.0340.60835.0670.1391.7705.8681.0100.81142.4450.080

Center

vs.

Center

10.1741.1900.3590.5882.4050.6290.5641.7580.3500.8863.4880.107

Center

vs.

Center

11.0722.9220.3241.5495.5100.0010.9892.6890.3251.4235.0820.002

Age

.5631.7550.3920.8133.7870.1520.1541.1660.3700.5652.4090.677

RA

duration

0.0070.9930.0150.9641.0230.6400.0101.0100.0140.9821.0390.491

RF

-LRB-

-RRB-

MTX

.0421.0430.0680.9131.1930.5350.0051.0050.0660.8841.1430.936

PSL

dose

Coef

coefficient

HR

OR

odds

ratio

SE

standard

error

CL

confidence

lower

limit

of

OR

CU

confidence

upper

limit

of

ORTable

from

the

logistic

regression

analysis

used

to

examine

the

factors

related

to

the

secondary

inefficiency

from

week

to

during

infliximab

therapyVariablesWeek

-LRB-

n

-RRB-

Week

-LRB-

n

-RRB-

Coef.ORSECLCUPCoef.ORSECLCUP

-LRB-

Intercept

-RRB-

Center

vs.

Center

0.0080.9920.3500.4991.9700.9810.0741.0770.4400.4552.5490.866

Center

vs.

Center

10.0711.0730.3330.5592.0600.8310.0541.0560.4260.4582.4330.899

.0191.0190.0110.9981.0420.0790.0321.0320.0141.0041.0620.028

Gender

0.2830.7530.3580.3731.5200.4290.2501.2840.5110.4713.5000.625

RA

duration

RF

-LRB-

-RRB-

0.2330.7920.3660.3871.6220.5240.1641.1780.5120.4323.2120.749

MTX

dose

0.0010.9990.0690.8731.1440.9900.0391.0400.0860.8791.2300.649

PSL

dose

0.0150.9850.0360.9181.0570.6820.0191.0190.0450.9341.1120.676DAS28-CRP

-LRB-

week

-RRB-

Coef

coefficient

HR

OR

odds

ratio

SE

standard

error

CL

confidence

lower

limit

of

OR

CU

confidence

upper

limit

of

OR

Discussion

The

study

was

designed

to

fully

evaluate

the

effect

of

infliximab

used

in

combination

with

MTX

on

the

clinical

results

during

a

study

period

in

DMARD-resistant

RA

patients

of

a

RA

management

group

in

Japan

The

safety

profile

of

infliximab

therapy

for

a

total

of

cases

was

investigated

in

Japan

using

an

all-case

registered

post-marketing

surveillance

system

and

the

entire

profile

of

adverse

events

related

to

infliximab

therapy

was

clearly

identified

-LSB-

-RSB-

The

assessment

of

efficacy

however

was

based

only

on

the

physician

's

general

evaluation

and

not

on

quantitative

measures

such

as

EULAR

criteria

In

this

report

therefore

efficacy

data

based

on

and

EULAR

improvement

criteria

were

intensively

assessed

The

average

before

starting

infliximab

was

it

decreased

to

at

week

and

it

remained

steady

at

by

week

after

the

infliximab

therapy

At

week

after

the

therapy

about

and

of

patients

satisfied

the

remission

and

low

disease

activity

criteria

respectively

and

these

effects

remained

-LRB-

and

respectively

-RRB-

by

week

Also

about

of

the

patients

exhibited

good

response

according

to

EULAR

criteria

continuously

from

week

to

These

results

reconfirmed

that

the

clinical

efficacy

of

infliximab

at

week

was

maintained

until

week

in

most

of

the

patients

treated

with

infliximab

Thus

appropriate

treatment

with

infliximab

and

MTX

in

this

study

group

could

minimize

secondary

insufficiency

of

the

therapy

for

at

least

one

year

On

the

other

hand

the

discontinuation

of

infliximab

was

observed

in

approximately

of

the

patients

during

the

period

This

rate

of

discontinuation

of

the

therapy

was

comparable

to

that

obtained

in

other

countries

in

the

Anti-Tumor

Necrosis

Factor

Trial

in

Rheumatoid

Arthritis

with

Concomitant

Therapy

-LRB-

ATTRACT

-RRB-

international

study

carried

out

in

the

USA

and

the

EU

in

a

German

domestic

study

and

in

a

French

group

study

during

the

first

one-year

period

-LSB-

-RSB-

Cumulative

hazards

differed

among

causes

of

discontinuation

discontinuations

due

to

adverse

events

inefficiency

remission

and

other

causes

-LRB-

including

changes

of

hospital/clinic

and

economic

problems

-RRB-

were

and

respectively

Male

gender

older

age

and

RF-negativity

were

significantly

correlated

with

discontinuation

of

infliximab

due

to

adverse

reactions

including

infusion

reactions

-LRB-

N

-RRB-

toxicoderma

-LRB-

-RRB-

bacterial

pneumonia

-LRB-

-RRB-

pneumocystis

jirovecii

pneumonia

-LRB-

-RRB-

but

more

than

two-thirds

of

the

withdrawals

due

to

adverse

events

were

observed

within

the

first

weeks

after

the

therapy

In

this

study

to

clarify

how

predisposing

factors

from

the

demographic

characteristics

of

RA

patients

were

related

to

the

clinical

efficacy

of

infliximab

therapy

a

multivariate

analysis

using

a

logistic

regression

was

performed

In

this

study

multiple

variables

including

sex

age

duration

of

disease

stage

class

positive/negative

RF

concomitant

MTX

dose

concomitant

PSL

dose

and

initial

levels

of

CRP

TJC

SJC

and

GH

were

assessed

It

is

worth

noting

that

among

multiple

variables

younger

age

RF-negativity

and

lower

levels

of

at

the

baseline

were

significantly

correlated

with

the

clinical

remission

induced

by

infliximab

therapy

at

week

These

results

imply

that

the

timely

use

of

MTX

and

infliximab

can

be

strongly

recommended

for

younger

RA

patients

that

show

RF-negativity

in

order

to

efficiently

achieve

clinical

remission

On

the

other

hand

male

gender

older

age

and

RF-negativity

were

significantly

correlated

with

discontinuation

of

infliximab

due

to

adverse

reactions

whereas

there

was

no

significant

factor

responsible

for

discontinuation

as

a

result

of

inefficacy

and

only

older

age

affected

secondary

insufficiency

from

week

to

after

the

infliximab

therapy

Although

it

is

intriguing

that

male

gender

predisposes

for

discontinuation

as

a

result

of

adverse

events

these

results

provide

the

first

information

that

can

be

used

to

facilitate

the

more

efficacious

use

of

infliximab

and

MTX

in

the

daily

practice

of

rheumatologists

Taken

together

this

study

reconfirms

the

clinical

efficacy

of

treatment

with

infliximab

and

MTX

in

Japanese

RA

patients

using

the

and

EULAR

response

criteria

Among

patients

with

active

RA

approximately

and

of

the

patients

satisfied

the

remission

and

low

disease

activity

criteria

and

good

response

according

to

the

EULAR

criteria

was

achieved

in

of

the

patients

treated

with

infliximab

plus

MTX

during

the

study

period

The

clinical

efficacy

of

infliximab

was

maintained

from

week

to

after

the

treatment

and

secondary

insufficiency

after

week

was

marginal

after

the

appropriate

treatment

in

this

study

group

Several

demographic

factors

including

male

gender

RF-negativity

and

lower

scores

of

were

significant

predisposing

factors

for

remission

The

promising

effectiveness

of

infliximab

at

improving

measures

of

disease

activity

in

RA

patients

has

led

to

this

therapy

becoming

one

of

the

key

advances

in

the

management

of

RA

Thus

this

study

is

important

because

it

provides

obvious

and

invaluable

evidence

concerning

the

efficacy

of

the

combinational

use

of

infliximab

and

MTX

and

can

guide

the

real

clinical

use

of

infliximab

in

the

future

O O O O O O O O O O O B O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B I O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B I O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O

rheumatoid arthritis
infliximab
eular response
retrospective study