Rheumatoid Arthritis, Lupus & IBD
A comprehensive analysis of the immunology clinical trial landscape — from competitive enrollment dynamics and treat-to-target design execution to biosimilar development, patient-reported outcomes integration, and the growing role of real-world evidence in autoimmune and inflammatory disease programs.
The Immunology Trial Landscape in 2026
Immunology represents one of the most active and competitive therapeutic areas in clinical development. The combination of large patient populations, well-characterized disease biology, and a robust pipeline of novel mechanisms has created an environment where multiple sponsors are simultaneously recruiting for similar indications — making enrollment strategy and site selection critical determinants of study success.
Rheumatoid arthritis (RA) continues to anchor the immunology portfolio with a steady stream of studies evaluating next-generation targeted therapies, biosimilar switching studies, and combination approaches. The RA landscape has matured significantly — with multiple approved biologics and JAK inhibitors available, new entrants must demonstrate differentiation through improved safety profiles, more convenient dosing, or efficacy in treatment-resistant populations, which translates into more restrictive eligibility criteria and smaller eligible patient pools.
Systemic lupus erythematosus (SLE) has experienced a renaissance in clinical development following the approval of belimumab and anifrolumab, with a pipeline that now includes over 30 agents in active clinical trials targeting novel pathways including type I interferon signaling, B-cell activating factor, plasma cell depletion, and complement inhibition. Lupus trials present unique enrollment challenges due to disease heterogeneity, flare-dependent study designs, and the need for organ-specific subpopulation stratification.
Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, represents one of the fastest-growing segments of the immunology pipeline. The evolution from systemic immunosuppression toward gut-selective therapies has opened new mechanism classes including S1P receptor modulators, gut-homing integrin inhibitors, and oral TYK2 inhibitors. IBD trials are uniquely demanding operationally, requiring endoscopic endpoints, central histopathology review, and frequent patient-reported outcome collection.
Key Performance Metrics
Network-wide benchmarks from our immunology portfolio highlight both the opportunities and the competitive pressures that define this therapeutic area.
Immunology studies benefit from large addressable patient populations, enabling a median enrollment rate of 2.3 patients per site per month across the portfolio. RA studies achieve the highest rates at 2.8 patients per site per month due to established rheumatology referral networks, while SLE studies average 1.4 per month due to more restrictive eligibility and disease heterogeneity. IBD studies average 2.1 per month with strong gastroenterology referral pipelines.
The average immunology site within our network is simultaneously participating in 4.2 active studies in the same therapeutic area, creating significant competition for eligible patients. This metric has increased from 2.8 five years ago, reflecting the growth of the immunology pipeline. Sites that actively manage competitive study balance and implement pre-screening protocols outperform sites that accept all available studies without capacity analysis.
Immunology sites achieve a median startup time of 12.4 weeks from contract execution to first patient enrolled, faster than the network-wide average of 14.8 weeks. This reflects the operational maturity of immunology-focused research sites, many of which have established regulatory relationships, pre-negotiated contract templates, and experienced coordinator teams that can onboard new studies efficiently.
The immunology portfolio achieves an 88% patient retention rate, among the highest in our network. This reflects the chronic, manageable nature of autoimmune conditions, strong patient motivation to access novel therapies, and well-established site-patient relationships in rheumatology and GI practices. Retention is highest in RA studies (91%) and lowest in Crohn's disease studies requiring repeated endoscopic procedures (82%).
Network Capabilities
Immunology trials require a specific combination of subspecialty clinical expertise, procedural capabilities, and laboratory infrastructure that distinguishes qualified immunology research sites from general clinical research organizations.
Rheumatology Subspecialty Sites
Our immunology network includes 34 dedicated rheumatology research sites staffed by board-certified rheumatologists with active clinical practices. This dual role as treating physician and clinical investigator is critical in immunology research — investigators who maintain active rheumatology practices have direct access to their own patient populations for study referral, understand the competitive therapeutic landscape from a prescribing perspective, and can make informed inclusion/exclusion assessments based on deep clinical experience. These sites maintain joint count training certification programs, ultrasound imaging capabilities for synovitis assessment, and DAS28/CDAI/SDAI scoring proficiency that ensures consistent disease activity measurement across the network.
GI Endoscopy Facilities
IBD clinical trials increasingly rely on endoscopic endpoints as primary or key secondary outcome measures, requiring sites with on-site or rapidly accessible endoscopy suites. Our network includes 18 sites with dedicated research endoscopy capabilities, including standardized video capture protocols for central reading, biopsy collection procedures aligned with study-specific histopathology requirements, and Mayo Endoscopic Score or SES-CD trained investigators. Sites coordinate with centralized endoscopy reading services to ensure consistent scoring across the network, with median turnaround times of 72 hours for central endoscopy reads.
For studies requiring serial endoscopy (baseline, induction endpoint, and maintenance endpoint), patient compliance with repeat procedures is a critical retention factor. Our sites implement patient education about the importance of endoscopic assessment, sedation preference management, and scheduling flexibility that accommodates patient preferences and reduces procedure-related anxiety.
Laboratory Infrastructure for Immunology Endpoints
Immunology studies require extensive laboratory monitoring including inflammatory biomarkers (CRP, ESR, calprotectin), autoantibody panels (RF, anti-CCP, ANA, anti-dsDNA, complement levels), immunoglobulin quantification, and specialized assays such as anti-drug antibody (ADA) testing and pharmacokinetic sampling. Our network sites maintain standardized specimen collection, processing, and shipping procedures with central laboratory partners, ensuring sample integrity across temperature-sensitive biomarkers. Local laboratory capabilities include same-day CBC with differential, CMP, and key inflammatory markers, enabling real-time safety monitoring and disease activity assessment.
Infusion & Subcutaneous Administration
The immunology portfolio includes both intravenous and subcutaneous biologic therapies, with an increasing trend toward subcutaneous self-administration in later-phase studies. Network sites maintain dedicated infusion suites for IV biologic administration with pre-medication protocols and infusion reaction monitoring, as well as patient training programs for subcutaneous self-injection using autoinjectors and prefilled syringes. Sites track injection technique competency through direct observation and provide retraining at specified intervals, ensuring consistent drug administration and reducing injection-related adverse events.
Enrollment Dynamics
Immunology enrollment dynamics are defined by the tension between large addressable patient populations and intense competition for eligible patients across a growing number of active studies. This competitive pressure fundamentally shapes enrollment strategy and site selection decisions.
The competitive enrollment landscape is the central challenge in immunology. In rheumatoid arthritis, for example, a typical metropolitan market may have 8-12 active RA studies competing for the same patient population at any given time. Patients who meet eligibility criteria for one study are very likely to meet criteria for multiple others, creating a situation where the first study to screen and enroll a patient captures that patient from the competitive pool. Sites that implement pre-screening algorithms, maintain patient registries, and proactively identify eligible patients from their clinical practice — rather than waiting for referrals — consistently outperform in competitive environments.
Treat-to-target trial designs, which require patients to have active disease despite current therapy, create a specific enrollment bottleneck. As the standard of care has improved with the availability of multiple effective biologic and targeted synthetic DMARDs, the pool of patients with moderate-to-severe active disease has contracted. Studies requiring patients to have failed 1-2 biologic DMARDs face a shrinking eligible population as more effective therapies are used earlier in the treatment algorithm. This dynamic is particularly acute in RA and is emerging in IBD as treat-to-target strategies gain adoption.
Biologic washout period requirements represent another enrollment friction point. Patients transitioning from one biologic therapy to a clinical trial often must undergo a washout period of 4-12 weeks depending on the prior therapy’s half-life, during which their disease may flare. Managing patient expectations during washout, providing appropriate bridging therapy where protocols allow, and minimizing the risk of disease flare-related dropout requires careful clinical management and clear patient communication.
Key Challenges in Immunology Trial Execution
The maturing immunology landscape presents operational complexities that require sophisticated site-level strategies and network-wide coordination.
Increasing Trial Complexity
Immunology protocols have become substantially more complex over the past decade. Modern RA and IBD studies may include induction and maintenance phases with re-randomization, dose titration algorithms based on disease activity thresholds, mandatory imaging or endoscopy at multiple timepoints, and stratification by prior therapy exposure and biomarker status. This complexity increases the training burden on site staff, the risk of protocol deviations, and the per-patient operational cost. Our network addresses this through protocol-specific training programs, decision-support tools that guide coordinators through complex visit algorithms, and centralized protocol deviation tracking that identifies systematic issues before they become widespread.
Biosimilar Competition for Patients
The explosion of biosimilar development in immunology has created parallel demand for the same patient populations targeted by innovator studies. Biosimilar switching studies, interchangeability trials, and pharmacokinetic bioequivalence studies all draw from the same pool of patients currently receiving reference biologic products. At many sites, biosimilar studies compete directly with innovator mechanism studies for enrollment. Our network manages this competition through transparent study portfolio management, patient registry pre-screening that identifies the best-fit study for each patient, and strategic study acceptance decisions that balance portfolio diversity with enrollment feasibility.
Patient-Reported Outcome Collection
Patient-reported outcomes (PROs) have evolved from secondary endpoints to co-primary or key secondary endpoints in immunology trials. Instruments such as HAQ-DI, FACIT-Fatigue, IBDQ, and SF-36 require consistent, timely completion by patients — yet PRO compliance rates vary widely across sites. Low compliance compromises endpoint assessment and can result in missing data that affects the interpretability of study results. Our network achieves PRO compliance rates above 92% through dedicated PRO training at enrollment, automated reminder systems, and real-time compliance monitoring that triggers coordinator follow-up when completion windows are at risk.
Flare-Based Study Design Challenges
Lupus and IBD studies frequently employ flare-based enrollment criteria, requiring patients to present with active disease flares during the screening window. The unpredictable timing of disease flares means that patients who are identified during periods of disease quiescence may need to be maintained in pre-screening registries for months until a qualifying flare occurs. This creates a long enrollment funnel with high attrition between pre-screening and formal screening. Our sites maintain active pre-screening registries with regular patient contact to identify flare events promptly, and flexible scheduling that enables rapid screening visits when qualifying flares are identified.
Real-World Evidence in Immunology
The integration of real-world evidence (RWE) with traditional randomized controlled trial data is transforming the immunology development landscape. Regulatory agencies, payers, and health technology assessment bodies are increasingly accepting RWE to supplement or extend RCT findings.
Registry Studies & Natural History Data
Disease registries provide longitudinal data on treatment patterns, disease progression, and outcomes in real-world clinical practice. Our network sites participate in major immunology registries including CORRONA (RA, PsA, SLE), SPARC IBD, and the Lupus Nephritis Trials Network. Registry participation provides investigators with access to natural history data that informs study design, establishes real-world comparator benchmarks, and supports external control arm construction for single-arm studies in rare autoimmune conditions.
Post-Market Surveillance & Effectiveness Studies
Following regulatory approval, many immunology products require post-market surveillance studies to monitor long-term safety, assess real-world effectiveness, and fulfill post-marketing commitments. These studies operate at the intersection of clinical research and clinical practice, requiring sites that can seamlessly integrate data collection into routine care workflows. Our network sites maintain structured data capture systems that enable efficient post-market study execution without disrupting standard patient care, achieving patient enrollment rates 40% higher than sites using traditional chart-abstraction approaches.
Hybrid RCT-RWE Study Designs
Emerging hybrid study designs combine elements of randomized controlled trials with real-world data collection. Pragmatic clinical trials, external control arm studies using real-world data, and adaptive platform trials with embedded RWE comparators are all gaining traction in immunology. These designs can reduce sample size requirements, accelerate enrollment, and generate evidence that is more generalizable to real-world clinical practice. Our network is currently supporting 4 hybrid RCT-RWE studies in immunology, with dedicated data management processes that maintain both GCP-compliant trial data and structured real-world data collection.
Pipeline Analysis
The immunology development pipeline continues to expand with novel mechanisms and increasingly differentiated therapeutic approaches.
Following safety signals that prompted regulatory scrutiny of first-generation JAK inhibitors, next-generation selective JAK inhibitors targeting JAK1, TYK2, or specific JAK combinations are in advanced development. These agents aim to preserve efficacy while improving cardiovascular, thrombotic, and malignancy safety profiles. TYK2 inhibitors in particular have shown promising results in psoriasis and are expanding into RA, IBD, and lupus indications.
The IL-17/IL-23 axis remains one of the most productive therapeutic targets in immunology, with agents in development across psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis. Novel approaches include dual IL-17A/F inhibitors, oral IL-23 antagonists, and combination strategies pairing IL-23 inhibition with gut-selective anti-inflammatory agents for IBD.
The principle of gut-selective immunomodulation — targeting immune pathways specifically within the gastrointestinal tract while minimizing systemic immunosuppression — has produced a new generation of IBD therapies. S1P receptor modulators, gut-homing integrin antibodies, and locally acting JAK inhibitors designed for topical colonic delivery represent a paradigm shift in IBD treatment that is reflected in an expanding clinical trial pipeline.
The development of oral formulations for biologic-class therapies represents a major convenience and adherence advantage over injectable or intravenous administration. Oral peptide delivery platforms, small molecule mimetics of biologic mechanisms, and gut-targeted delivery systems are in various stages of clinical development across RA, IBD, and psoriasis. These programs present unique pharmacokinetic study requirements including food-effect studies, dose-finding with exposure-response modeling, and formulation bridging studies.
Autologous CD19 CAR-T cell therapy has shown remarkable results in treatment-refractory systemic lupus erythematosus and systemic sclerosis, achieving deep and durable remissions in early clinical studies. This emerging modality is expanding into controlled clinical trials across multiple autoimmune indications. Sites participating in these programs require apheresis capabilities, lymphodepletion chemotherapy administration, and CRS monitoring infrastructure — capabilities traditionally associated with oncology rather than immunology sites.
The biosimilar pipeline in immunology remains robust, with development programs targeting adalimumab, tocilizumab, ustekinumab, and other reference biologics as patents expire. Biosimilar studies have specific design requirements including pharmacokinetic bioequivalence studies, clinical equivalence trials with equivalence margins, immunogenicity comparisons, and switching/interchangeability studies. These programs create parallel demand for the same patient populations targeted by innovator studies, intensifying competitive enrollment pressure.
Patient-Reported Outcomes Integration
Patient-reported outcomes have evolved from supplementary data collection to a central component of immunology regulatory submissions and health technology assessment dossiers. Regulatory agencies and payers increasingly require demonstration that clinical improvements translate into meaningful changes in patient experience, functional capacity, and quality of life.
The complexity of PRO collection in immunology studies has grown substantially. Modern protocols may include 6-10 PRO instruments administered at multiple timepoints, creating a cumulative assessment burden that can take 30-45 minutes per visit. Instruments span disease-specific measures (HAQ-DI for RA, IBDQ for IBD, SLEDAI for lupus), symptom-specific measures (pain VAS, fatigue NRS), generic health status measures (SF-36, EQ-5D), and work productivity measures (WPAI). Ensuring consistent, complete collection of this multi-instrument battery requires dedicated PRO management processes at the site level.
Our network has implemented a comprehensive PRO excellence program that includes eCOA platform standardization across sites, patient training at enrollment with comprehension verification, real-time compliance dashboards visible to coordinators and site managers, and escalation protocols when patients miss completion windows. This program has reduced PRO-related data queries by 65% and improved completion rates from 78% to 93% across the immunology portfolio.
Discuss Your Immunology Program
Connect with our team to explore rheumatology and GI site capabilities, competitive enrollment strategies, and real-world evidence integration for your immunology clinical development program.