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Filgotinib is an oral Janus kinase 1 (JAK1) preferential inhibitor approved for adult patients with moderate-to-severe active rheumatoid arthritis (RA) who have responded inadequately to, or who are intolerant of, one or more disease-modifying antirheumatic drugs (DMARDs). While randomised trials have demonstrated its efficacy and tolerability, real-world data on very early treatment effects—particularly on pain relief, fatigue and function—remain scarce. The FIRST-RA study was initiated to address this evidence gap under routine care conditions.
Methods
FIRST-RA is a prospective, multicentre, non-interventional cohort study in Germany and Austria. Approximately 300 adult patients with RA newly starting filgotinib are enrolled and followed for 24 weeks. Patients are stratified into three groups based on prior use of advanced therapies (AT; biologic [b]DMARDs or targeted synthetic [ts]DMARDs): AT-naïve, one prior AT and ≥ 2 prior ATs. Clinical assessments are conducted at baseline and weeks 4, 12 and 24. Patient-reported outcomes (PROs), including the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire, are captured electronically or on paper— daily during week 1 and at regular intervals thereafter.
Planned Outcomes
The primary endpoint is the change in RAID pain score from baseline to week 4 (or earlier). Secondary endpoints include fatigue, disease activity, morning stiffness, treatment satisfaction and tolerability. Additional analyses will investigate very early symptom changes, drug utilisation patterns and treatment persistence, as well as effectiveness within AT exposure subgroups (AT-naïve and AT-experienced), summarised descriptively without formal subgroup testing.
An exploratory, descriptive analysis will examine how the 2023 label update for JAK inhibitors may have influenced patient characteristics, prescribing patterns and safety outcomes, using the earlier-enrolled FILOSOPHY real-world cohort as an external reference.
FIRST-RA is the first real-world study to capture very early symptomatic responses to filgotinib. By integrating PRO data with clinical outcomes, the study aims to support personalised RA management and clarify the use of filgotinib in today’s clinical practice.
Prior presentation: Pongratz G, Witte T, Alten R, Pausch C, Reinhold R, Pittrow D, Burmester GR. Rationale, design and methods of the novel Filgotinib Initial Response Study in Rheumatoid Arthritis (FIRST-RA). Poster presentation at the 53rd Scientific Meeting of the German Society for Rheumatology (DGRh). Wiesbaden, 17–20 September 2025. Abstract published in: German Medical Science GMS Publishing House; 2025. DocRA.01. DOI: 10.3205/25rhk130.
Key Summary Points
FIRST-RA is an open, non-controlled, routine-care, non-interventional study of filgotinib (Jyseleca®). Its external validity will be assessed by benchmarking against the FILOSOPHY dataset.
This real-world study charts very early trajectories of pain, fatigue and other patient-reported outcomes (PROs) immediately after starting filgotinib.
Patient engagement is intensive, with PROs collected daily in the first week, weekly during the first month and monthly through Month 6, complemented by routine clinical visits.
This high-resolution schedule enables precise characterisation of very early symptomatic change and patient satisfaction, alongside disease activity measures (28-joint Disease Activity Score based on C-reactive protein [DAS28-CRP] and Clinical Disease Activity Index [CDAI]).
Findings are intended to inform early counselling, shared decision-making and treat-to-target strategies under routine care conditions.
Introduction
Background
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease primarily affecting the joints and synovial tissue. Its pathogenesis involves persistent immune activation and chronic inflammation, driven by a complex network of cytokines and intracellular signalling pathways, notably the Janus kinase (JAK) family [1‐3]. Over time, RA can lead to progressive joint destruction, extra-articular manifestations and comorbidities that substantially impair physical function and health-related quality of life, and may even increase mortality [4].
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Beyond structural damage and inflammation, RA imposes a substantial symptomatic burden. Patients frequently report persistent pain, fatigue, stiffness and physical limitations, even when clinical inflammation appears controlled [5, 6]. Among these, pain is one of the most debilitating symptoms—often persisting despite low disease activity or remission. This discrepancy between clinical indicators and patient experience underscores the limitations of conventional disease activity metrics in capturing the full burden of disease [7‐9].
The RA treatment landscape has evolved significantly over the past 3 decades. In addition to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, treatment options now include biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), which interfere with intracellular signalling cascades downstream of cytokine receptors [10]. Collectively, bDMARDs and tsDMARDs are referred to as advanced therapies (ATs).
Filgotinib is an oral JAK1 preferential inhibitor that has demonstrated efficacy in reducing signs and symptoms of RA, improving physical function and achieving remission across diverse patient populations—including those with inadequate response to methotrexate (FINCH 1) [11], prior biologic failure (FINCH 2) [12] and methotrexate-naïve patients (FINCH 3) [13]. It received marketing authorisation in the European Union in September 2020 for the treatment of adult patients with moderate-to-severe active RA who have responded inadequately to, or are intolerant of, one or more DMARDs. Filgotinib may be used as monotherapy or in combination with methotrexate. In March 2023, the European label for all JAK inhibitors, including filgotinib, was updated (cautious use in ≥ 65 years, current/past smokers, high cardiovascular or malignancy risk, prior venous thromboembolism [VTE]; risk-benefit assessment and dose consideration) [14].
The Filgotinib Initial Response Study in Rheumatoid Arthritis (FIRST-RA) is being conducted under this revised label, reflecting current prescribing conditions in routine clinical practice, and aims to build upon existing real-world use data [15, 16] by providing additional insights into early treatment responses.
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Objectives
Primary objective:
The primary objective of the FIRST-RA study is to evaluate the early benefit of filgotinib on pain, measured by the pain domain of the Rheumatoid Arthritis Impact of Disease (RAID) score (self-assessment by patient on diary) at week 4 (or earlier), as absolute change compared with baseline.
Secondary objectives are as follows:
To describe baseline characteristics of patients receiving filgotinib, including socio-demographic characteristics, comorbidities, reason for treatment initiation, RA disease characteristics, previous RA medications, reasons for treatment changes and concomitant medications.
To evaluate the early benefit of filgotinib on disease activity and inflammation, measured with the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) and Clinical Disease Activity Index (CDAI) at week 4 (or earlier), compared with baseline.
To evaluate the early benefit of filgotinib on fatigue, measured by the fatigue domain of the RAID (self-assessment by patient on diary) at week 4 (or earlier), as absolute and percent change from baseline.
To describe effectiveness of filgotinib in AT-naïve and AT-experienced subgroups (1 prior and 2 + prior), measured by RAID, DAS28-CRP/CDAI and morning stiffness over time; no formal subgroup hypothesis testing is planned.
To describe the effectiveness of filgotinib over 24 weeks of treatment, measured by change from baseline in RAID, DAS28-CRP/CDAI and morning stiffness, in patients newly started on filgotinib in this study.
To describe the tolerability of filgotinib in patients newly started on treatment. Findings will be put into perspective with the real-world FILOSOPHY study (NCT04871919). Tolerability will be assessed by the frequency, type and severity of:
adverse drug reactions (ADR) and serious adverse drug reactions (SADR)
adverse events of interest, including serious and opportunistic infections (including herpes zoster), major adverse cardiovascular events (MACE), VTE, hyperlipidemia, malignancies, non-melanoma skin cancer (NMSC), gastrointestinal (GI) perforation and fractures
To assess patient satisfaction with filgotinib over time using two RABBIT items (see details below).
Additional exploratory objectives of this study are:
To evaluate the early benefit of filgotinib on pain, fatigue and inflammation at week 4 compared with baseline using RAID and DAS28-CRP and/or CDAI.
To record details of drug utilisation patterns over the 24-week treatment period, with focus on reasons for treatment initiation in patients newly started on filgotinib, use of filgotinib in monotherapy versus in combination therapy, concomitant medication, use of corticosteroids/tapering, changes from use of filgotinib in combination with csDMARD to filgotinib as a monotherapy and vice-versa, reasons for treatment interruptions and discontinuation, and treatment persistence probability over time.
To put patient characteristics and effectiveness into perspective with the real-world cohort from the FILOSOPHY study—specifically for patients who initiated filgotinib prior to the March 2023 label update.
These objectives will be assessed in the overall study population and within clinically relevant subgroups to support the development of individualised treatment strategies with filgotinib in a real-world setting. The corresponding study endpoints derived from these objectives are presented in Table 1.
Table 1
Endpoints
Category
Endpoint
Primary endpoint
Absolute change from baseline to week 4 (or earlier) in the pain domain of the RAID score (patient self-assessment)
Secondary endpoints
Change in RAID fatigue domain at week 4 (or earlier) and at later time points (weeks 12 and 24), reported as absolute and percent change from baseline
Change in DAS28-CRP or CDAI at week 4 (or earlier) and at later time points (weeks 12 and 24)
Baseline patient characteristics—Subgroup analyses including effectiveness measures in these subgroups over time (AT-naïve, 1 prior AT, ≥ 2 prior ATs)
Frequency and type of ADRs, SADRs and adverse events of interest (e.g. infections, MACE, VTE)
Treatment satisfaction using RABBIT items
Exploratory endpoints
Daily RAID pain data (day 0–7): very early treatment response
Treatment persistence at weeks 12 and 24 (time-to-event and Kaplan-Meier analysis)
Treatment patterns: monotherapy vs. combination, corticosteroid use/tapering, dose changes, discontinuation
Reasons for initiation and discontinuation of filgotinib
Use of additional PROs if available in clinical routine
Put findings in perspective with FILOSOPHY real world cohort (pre-/post-label update in March 2023)
ADR, adverse drug reaction(s); AT, advanced therapy; CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; DAS28-CRP, Disease Activity Score using 28 joints and CRP; MACE, major adverse cardiovascular event(s); PRO, patient-reported outcome(s); SADR, serious adverse drug reaction(s); RAID, Rheumatoid Arthritis Impact of Disease; VTE, venous thromboembolism.
Methods
Study Design
FIRST-RA is a prospective, multicentre, non-interventional cohort study conducted at approximately 30 rheumatology centres in Germany and Austria. The study reflects routine clinical care; no treatment or diagnostic procedures are mandated beyond standard practice.
Filgotinib (Jyseleca®; Alfasigma S.p.A., Bologna, Italy) is prescribed independently by the treating physician, in accordance with the current product label. Only patients newly initiating filgotinib are eligible for enrolment. The study does not influence therapeutic decisions or enforce specific treatment algorithms. The first patient was enrolled on 6 May 2025, and the planned study end is 31 December 2026.
Sample Selection
Eligibility criteria are shown in Table 2. “Moderate to severe RA” is defined per the Jyseleca® label and not specified further by DAS28 or CDAI cut-off values. RA diagnosis follows German clinical practice, which applies the 2010 ACR/EULAR classification criteria [6]. A total of approximately 300 patients will be enrolled and stratified into three subgroups of roughly equal size:
AT-naïve: No prior use of bDMARDs or tsDMARDs
One prior AT: Previously treated with one bDMARD or tsDMARD
Multiple prior ATs: Previously treated with ≥ 2 bDMARDs or tsDMARDs
Table 2
Eligibility criteria
Inclusion criteria:
Adults with a diagnosis of moderate-to-severe active rheumatoid arthritis
Patients initiating filgotinib treatment for the first time, in accordance with the approved label
Ability and willingness to use an electronic device for completing study questionnaires
Signed informed consent prior to any study-related documentation
Exclusion criterion:
Participation in an interventional study (inclusion in registries such as RABBIT is allowed)
To ensure analytical robustness, recruitment caps may be introduced if one subgroup becomes disproportionately large.
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Measurements
The overall study flow is illustrated in Fig. 1, with study procedures and assessments detailed in Table 3. Clinical assessments are scheduled at baseline and at weeks 4, 12 and 24, while patient-reported outcomes (PROs) are more frequently collected electronically (daily from day 0 to day 7; weekly through week 4; and monthly through week 24) to capture early and longitudinal treatment effects.
Fig. 1
Study flow. PRO: patient-reported outcome; RA: rheumatoid arthritis; RAID: Rheumatoid Arthritis Impact of Disease score.
Filgotinib discontinuationb or early study termination
Baselinea
Day 0, Days 1–7, weeks 2, 3, 4,
8, 12, 16, 20 and 24
Weeks 4, 12 and 24
Documentation by
Physician
Patient
Physician
Physician
Informed consent
X
X
Socio-demographic characteristics (including age, sex, ethnicity, current employment status, work type and educational status)
X
Weight, height and body mass index
X
Smoking status (current/past smoking status)
X
RA disease (details)
X
X
Prior RA treatmentc
X
Medical history
X
Comorbidities
X
Filgotinib RA treatmentd
X
X
X
Concomitant medications for comorbid conditions (drug name, dose, regimen, start/end date), including corticosteroids dose
X
X
X
Filgotinib discontinuation (date of discontinuation and reinitiation, reasons)
X
Tender joint score (0–28)
X
X
X
Swollen joint score (0–28)
X
X
X
Patient Global Assessment (0–10)
X
X
X
Physician Global Assessment (0–10)
X
X
X
DAS28-CRP
X
X
X
CDAI
X
X
X
C-reactive protein
X
X
X
Serology (RF, ACPA)e
X
ADRf, SADR, SSRs and adverse events of interest (teratogenicity, MACE, hyperlipidemia, herpes zoster, varicella zoster, malignancies, NMSC, VTE, serious and opportunistic infections, GI perforation and fractures)
ACPA, anti-citrullinated protein antibodies; ADR, adverse drug reaction(s); CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; DAS28-CRP: 28-joint Disease Activity Score based on C-reactive protein; eCRF, electronic case report form; EDC, electronic data capture; ePRO, electronic patient-reported outcome; GI, gastrointestinal; MACE, major adverse cardiovascular event(s); NMSC, non-melanoma skin cancer; PRO, patient-reported outcome; RA, rheumatoid arthritis; RAID, Rheumatoid Arthritis Impact of Disease; RF, rheumatoid factor; SADRs, serious adverse drug reaction(s); SSR, special situation report (e.g. pregnancy, medication error, off-label use, overdose); VTE, venous thromboembolism
Day 0 = day before filgotinib; Day 1 = filgotinib initiation
aWithin approximately 30 days prior to first dose
bPatients discontinuing filgotinib may remain in the study and will be followed up until reaching the defined end of the study (i.e. 24 weeks after enrollment) or until documented premature end (e.g. due to loss to follow-up, withdrawal of consent or death)
cBiologics will be queried by group (tumour necrosis factor inhibitors, interleukin-6 receptor inhibitors, abatacept, rituximab) without specifying therapy initiation or end dates. JAK inhibitors will be queried by substance (upadacitinib, tofacitinib, baricitinib) without specifying therapy initiation or end dates. csDMARDs will be queried by active substance (methotrexate, leflunomide, sulfasalazine, hydroxychloroquine) without specifying therapy initiation or end dates. Corticosteroid use in prior therapy will not be queried, as it is considered standard practice. The most recent therapy prior to filgotinib initiation will be documented, including therapy initiation and end dates
dReasons for starting filgotinib, treatment target (remission/low disease activity/other), filgotinib monotherapy or combination (including DMARDs and/or corticosteroids), regimen, dose, dose change and reason for dose change
eRheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positive, negative or unknown (only at baseline)
fIf an ADR is ongoing at the time of the last follow-up visit, the investigator needs to follow-up on the patient until event resolution or reasonable stabilisation and to document in the patient’s source documentation
gPRO questionnaires to be completed remotely by the patient using electronic devices OR in exceptional cases on patient diaries and entered by the site personnel (i.e. study nurse) into the database. For visits at baseline and weeks 4, 12 and 24, results will in any case be entered by the site staff into the eCRF
hIf used as part of the site’s routine practice, it will be completed by the patient on paper, and the data will be entered into the EDC by the site staff
Data are collected using electronic case report forms (eCRFs) and include:
Demographics and clinical history
Disease characteristics and serology
Prior and concomitant medications (including corticosteroids)
Clinical disease activity (DAS28-CRP, CDAI and joint counts)
Laboratory parameters (e.g. CRP)
Safety outcomes (ADRs, SADRs and pre-defined adverse events of interest)
PROs (RAID score, morning stiffness and treatment satisfaction)
No additional laboratory tests or procedures beyond routine clinical care are required.
Patient-Reported Outcomes
PROs are completed by patients on their own electronic devices using an online ePRO that writes directly to the study’s electronic data capture (EDC)/eCRF. At the scheduled site visits (baseline and weeks 4, 12 and 24), site staff verify the entries and, if needed, enter the PRO values into the eCRF. If electronic entry is not possible, patients use paper diaries as back-up; the diaries are collected and transcribed by site personnel into the database. Completion time per assessment is approximately 5–10 min.
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RAID Score
The Rheumatoid Arthritis Impact of Disease (RAID) score assesses seven domains: pain, fatigue, physical function, sleep, physical and emotional well-being, and coping [17, 18]. Each domain is rated on a 0–10 numeric rating scale, where higher scores indicate greater disease impact.
Treatment Satisfaction
Treatment satisfaction is assessed at each time point using two RABBIT-style items [19]—satisfaction with effectiveness and with tolerability—and recorded in four ordered categories: very satisfied, rather satisfied, rather unsatisfied or very unsatisfied.
Morning Joint Stiffness
Assessed by a “yes/no” question. If present, patients report the duration in minutes.
Effectiveness criteria
Tender Joint Count (TJC)
Tender joint counts are based on a standardised 28-joint assessment, including shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints and knees [20]. Each joint is evaluated for tenderness upon palpation or movement. Artificial joints are excluded.
Swollen Joint Count (SJC)
The same 28 joints are assessed for swelling, with artificial joints excluded. The presence of synovial swelling is recorded based on clinical examination.
Patient Global Assessment (PtGA)
Patients rate their current overall disease impact by answering the PtGA, which captures the patient’s overall perception of their disease activity. Patients are asked to rate their current disease activity on a numerical rating scale (NRS) ranging from 0 to 10, where 0 indicates no disease activity and 10 indicates very high disease activity. Responses are to be given as whole numbers. If a response is not available, this is recorded accordingly.
Physician Global Assessment (PhGA)
Physicians assess overall disease activity using clinical judgment based on signs, symptoms and physical function. The following prompt is used: “How would you rate the disease activity?”
Responses are scored on NRS ranging from 0 to 10, where 0 indicates no disease activity and 10 indicates maximal disease activity.
DAS28-CRP
DAS28 with CRP (an acute phase reactant) is a validated composite index used to quantify inflammatory disease activity [21].
Clinical Disease Activity Index (CDAI)
The CDAI is a simplified composite score comprising TJC, SJC, PtGA and PhGA. It does not require laboratory parameters and allows disease activity assessment at any time point. CDAI correlates well with functional outcomes and joint damage, and it is often used in daily clinical practice [22, 23].
In FIRST-RA, physicians may choose between DAS28-CRP and CDAI based on clinical preference. The treating physician calculates the CDAI as part of routine care and manually enters the index value into the eCRF; the eCRF does not auto-calculate CDAI from its components. If the CDAI is not available at a visit, this is recorded as “value not available”.
Inflammation Biomarkers
CRP will be recorded as part of routine clinical assessments to monitor systemic inflammation. No additional study-specific laboratory testing is required.
Data Analysis
Sample Size Calculation
The sample size was determined to detect a mean change of 1.0 point in the RAID pain score with 80% power (α = 0.05), assuming a standard deviation of 2.5 using a one-sided paired-sample t-test. A minimum of 41 evaluable patients would be required for this analysis. Accounting for an estimated 5% dropout rate and up to 10% of patients with incomplete primary endpoint data (i.e. missing pain score at baseline or week 4), approximately 49 patients per subgroup are needed. To ensure robustness across treatment strata and enable precise descriptive subgroup summaries, a total of ~ 300 patients will be enrolled. In case these assumptions are optimistic, the observed variability and rates of missing data and dropout will be prospectively monitored during enrolment. Should these parameters deviate materially from the assumptions, the recruitment target will be increased to maintain the planned precision overall and within treatment strata.
General Analytical Approach
Given the non-interventional nature of the study, analyses will be primarily descriptive. Results will be summarised for the total population and stratified by predefined subgroups (e.g. AT-naïve vs. AT-experienced) and relevant covariates such as age, sex, body mass index, disease duration and prior therapies. Continuous variables will be summarised using mean, standard deviation, median, interquartile range and range, while categorical variables will be presented as absolute and relative frequencies, with 95% confidence intervals (CIs) where appropriate. All analyses will be conducted using validated software (e.g. SAS, R or SPSS). Missing data for the primary endpoint will be handled primarily using complete case analysis, with sensitivity analyses applying multiple imputation under the assumption of missing at random. A detailed Statistical Analysis Plan (SAP) will be finalised before database lock.
Primary Endpoint Analysis
The change in RAID pain score from baseline to week 4 (or earlier) will be analysed using a one-sided paired t-test, as the study is designed to detect improvement in the expected direction based on consistent evidence from prior randomised trials and real-world studies of filgotinib. This directional testing approach increases statistical power for confirming benefit under the anticipated effect direction. In case of non-normal distribution, a non-parametric alternative (e.g. Wilcoxon signed-rank test) will be used in sensitivity analyses.
Secondary and Exploratory Endpoint Analysis
Changes in fatigue (RAID), disease activity (DAS28-CRP, CDAI) and patient satisfaction will be analysed analogously to the primary endpoint. Categorical outcomes (e.g. the proportion of patients achieving RAID < 2.0, DAS28-CRP remission [defined as DAS28-CRP < 2.6] or low disease activity [i.e. DAS28-CRP < 3.2]) will be reported descriptively.
Subgroup comparisons (e.g. treatment response by AT exposure or pre-/post-label update) will be descriptive; no formal hypothesis testing is planned.
Early-response analyses will be anchored to initiation of the index JAK inhibitor (Jyseleca®). In this short 6-month window, the effect of the newly initiated treatment is awaited first; hence, concomitant DMARD initiation or escalation before the first response assessment is expected to be infrequent. Any such changes will be recorded and handled via time-varying covariates or censoring, with robustness examined in sensitivity analyses excluding these cases and in the (expectedly small) subgroup with concurrent filgotinib initiation and DMARD start or escalation.
For non-naïve patients, the duration of each prior advanced therapy and the reason for discontinuation—categorised as primary failure (no meaningful initial response), secondary failure (loss of response after initial benefit), adverse events or other—will be recorded. These variables will be included as covariates in adjusted analyses and used to define prespecified subgroups for descriptive summaries and sensitivity analyses.
Persistence analyses will use Kaplan-Meier estimators.
Adverse events will be summarised as event rates per patient and per exposure time, stratified by seriousness and severity.
Control of Confounding
To address potential confounding (e.g. indication bias), baseline characteristics will be summarised across subgroups, and, where appropriate, exploratory multivariable regression models adjusted for key covariates (such as age, sex, disease duration, comorbidities and prior therapies) will be used to support interpretation.
External Reference Cohort
Where applicable, patient characteristics, prescribing patterns and safety outcomes from the study will be descriptively put into perspective with the FILOSOPHY study. For these comparisons, variables will be harmonised by aligning definitions, coding schemes and assessment time windows across both datasets, following the original data dictionaries of each study.
Data Management and Monitoring
Data are captured using a validated EDC system. Built-in plausibility checks, comprehensive site training and regular central data reviews will ensure data quality and consistency. Patient confidentiality and data protection are maintained in accordance with applicable data privacy laws.
Strengths and limitations
FIRST-RA is a prospective, non-interventional study designed to evaluate early symptomatic treatment responses to filgotinib under real-world conditions in patients with moderate-to-severe active RA. While the pivotal FINCH randomised clinical trials demonstrated filgotinib’s efficacy and safety across diverse RA populations, [11, 12, 24] they provide limited information on symptom dynamics during the crucial early treatment phase. This gap is relevant for both patients and clinicians, as early improvement often shapes perceptions of treatment success and influences long-term adherence.
Pain in RA is multifactorial, involving both inflammatory and non-inflammatory mechanisms such as central sensitisation, structural joint damage and psychosocial factors [25‐27]. Notably, many patients report persistent pain despite achieving clinical remission or low disease activity based on standard composite indices like DAS28 or CDAI [28]. This dissociation highlights the need to assess outcomes that better reflect the patient experience, particularly pain, fatigue and functional impairment.
As clinical recommendations increasingly emphasise PROs as complementary endpoints [29], tools such as the RAID score have gained prominence in both research and routine practice [30, 31]. In Germany, rheumatologists have shown strong interest in integrating electronic PRO (ePROs) into care, driven by their utility in monitoring treatment effects and disease progression [32]. FIRST-RA capitalises on this momentum by integrating structured ePROs into its study design. Through high-frequency data capture, the study aims to provide a nuanced picture of the patient’s experience—particularly during the early phase of treatment. In addition to pain and fatigue, FIRST-RA evaluates inflammation, morning stiffness, treatment satisfaction and tolerability from the patient’s perspective. By doing so, it not only complements clinical assessments but also reflects the multidimensional nature of RA.
The inclusion of patients initiating treatment after the March 2023 label update for JAK inhibitors is another strength. This update introduced new safety warnings and narrowed the eligible patient population based on age, cardiovascular risk and malignancy history [14]. By focusing on patients treated in contemporary routine care, FIRST-RA therefore reflects current clinical reality and allows for the evaluation of filgotinib under stricter safety conditions. On the other hand, accumulating real-world experience with filgotinib further encouraged its adoption in routine clinical practice, despite these tightened criteria.
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The absence of an internal control group is typical of product-focused real-world evidence and reflects ethical and practical constraints, as treatments in routine care cannot be withheld or randomised solely to create a comparator arm. To contextualise the findings of the present study, external validation will be undertaken by comparing outcomes with contemporaneous studies in similar settings and patient populations (e.g. FILOSOPHY and studies of other JAK inhibitors).
The planned descriptive comparison with historical data from the FILOSOPHY real-world study [15] may help to explore how the March 2023 label update influenced prescribing patterns and patient characteristics. While the non-randomised nature and limited follow-up duration restrict definitive conclusions regarding treatment outcomes, this analysis may still provide useful context for interpreting trends in clinical practice and generating hypotheses for future research.
The study design of FIRST-RA also allows for subgroup analyses across different treatment histories—namely, patients naïve to advanced therapies and those previously exposed to bDMARDs or tsDMARDs. These comparisons are increasingly relevant given ongoing discussions on the optimal sequencing of targeted agents and the role of JAK inhibitors in early versus refractory disease.
As with any observational study, FIRST-RA faces inherent limitations such as potential selection bias, absence of randomisation and missing data. Several design elements aim to mitigate these challenges, including use of ePROs to reduce recall bias, structured assessment schedules and plans for robust statistical approaches. Importantly, the study is embedded in routine care and avoids imposing additional procedures, thereby enhancing generalisability and relevance. The combined use of clinical measures and patient-reported data will deliver meaningful insights into both the physiological and subjective dimensions of treatment response.
Ethics
The Ethics Committee of the Saxony State Chamber of Physicians in Dresden approved the study (EK-BR-2/25-1) on 28 March 2025. The ethics committees of the State Chambers of Physicians in North Rhine (2025115, 18 July 2025) and Baden-Württemberg (B-F-2025-058, 30 October 2025) subsequently acknowledged this approval. Additional local ethics committees accepted the lead vote according to the “one study-one vote” procedure. The FIRST-RA study is conducted in accordance with the Declaration of Helsinki, Good Pharmacoepidemiology Practices (GPP), Good Pharmacovigilance Practices (GVP) and applicable regulatory requirements in Germany and Austria. The study is registered in the German Clinical Trials Register under DRKS00036136. It is also registered with the Federal Institute for Drugs and Medical Devices (BfArM) under NIS 7864. All participants provide written informed consent before any study-related documentation is performed.
Dissemination
Findings will be disseminated through peer-reviewed publications and presentations at national and international rheumatology meetings. Outputs will follow a predefined analysis and publication plan; authorship will adhere to ICMJE criteria. The protocol, amendments and SAP will be made available as supplementary material or via a public repository.
Conclusion
Conducted in Germany and Austria, FIRST-RA is the first real-world study to systematically evaluate early symptomatic treatment responses to filgotinib using repeated ePROs. By integrating daily and longitudinal PRO data with standard clinical assessments, the study aims to generate detailed insights into pain trajectories, treatment satisfaction, disease activity and tolerability during the first weeks and months of therapy.
Furthermore, by including patients treated in accordance with the updated European label for JAK inhibitors, FIRST-RA reflects current prescribing practices and will provide valuable context for interpreting treatment effects in this population. Descriptive comparisons with the FILOSOPHY study for patient characteristics, treatment patterns and safety outcomes may also offer insights into how the 2023 regulatory update influenced the clinical use of filgotinib.
Through its pragmatic design, structured subgroup analyses and focus on outcomes that matter to patients, FIRST-RA is therefore expected to inform personalised treatment strategies and support evidence-based use of filgotinib in routine rheumatology care.
Medical Writing/Editorial Assistance
Publications management was provided by Matthew deSchoolmeester, PhD, ISMPP CMPP, Aspire Scientific, Manchester, UK, and funded by Alfasigma S.p.A.
Declarations
Conflict of Interest
Georg Pongratz has received consultancy fees and speaker fees from AbbVie, Alfasigma, Boehringer Ingelheim, Eli Lilly & Co., Galapagos, Pfizer, Roche, Sanofi, Viatris and Vertanical. Rieke Alten has received consultancy fees and speaker fees from AbbVie, Alfasigma, Amgen, Biogen, BMS, Celltrion, Chugai, Eli Lilly & Co., Galapagos, Gilead, Hexal, Janssen, Novartis, Pfizer, Roche, UCB and Viatris. Torsten Witte has received consultancy fees and speaker fees from AbbVie, Alfasigma, Eli Lilly & Co. and Pfizer. Christine Pausch has no conflicts of interest. Robert Reinhold is an employee of Alfasigma GmbH. David Pittrow has received consultancy fees from Alfasigma, Amgen, Aspen, Bayer, Biogen, Boehringer Ingelheim, Daiichi Sankyo, MSD, Sandoz/Hexal, Sanofi-Genzyme, Takeda, Viatris and Zambon. Gerd R. Burmester has received consultancy fees and speaker fees from AbbVie, Alfasigma, BMS, Eli Lilly & Co., Galapagos, Janssen, Novartis, Pfizer, Sanofi and UCB.
Ethical Approval
The Ethics Committee of the Saxony State Chamber of Physicians in Dresden approved the study (EK-BR-2/25-1) on 28 March 2025. The ethics committees of the State Chambers of Physicians in North Rhine (2025115, 18 July 2025) and Baden-Württemberg (B-F-2025-058, 30 October 2025) subsequently acknowledged this approval. Additional local ethics committees accepted the lead vote according to the “one study – one vote” procedure. The FIRST-RA study is conducted in accordance with the Declaration of Helsinki, Good Pharmacoepidemiology Practices (GPP), Good Pharmacovigilance Practices (GVP) and applicable regulatory requirements in Germany and Austria. The study is registered in the German Clinical Trials Register under DRKS00036136. It is also registered with the Federal Institute for Drugs and Medical Devices (BfArM) under NIS 7864. All participants provide written informed consent before any study-related documentation is performed.
Open Access
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