Janssen Research & Development, LLC

The VOYAGE 1 and 2 studies of guselkumab in moderate-to-severe psoriasis are among the first studies of biologics to include patients with a history of malignancy. In these studies, 18 guselkumab-treated patients had a history of malignancy (excluding nonmelanoma skin cancer) >5 years prior to enrolment. These 18 patients were exposed to guselkumab for up to 5 years; during this time, 1 patient had a recurrence of bronchial carcinoma, and 3 patients developed new malignancies (breast cancer, melanoma, and sebaceous carcinoma). All patients with new or recurrent malignancies had underlying risk factors for malignancy. Overall, results of this analysis in a small population of patients with a history of malignancy support the favourable long-term safety profile of guselkumab.

A IM : to evaluate efficacy and safety of ustekinumab in Russian patients with ulcerative colitis in UNIFI study. PATIENTS AND METHODS: the UNIFI program (CNTO1275UCO3001) consisted of two randomized placebo-controlled trials: an 8-week induction study and a 44-week maintenance study and long-term period. This analysis included patients from 14 Russian centers. RESULTS : the induction study of the UNIFI program enrolled 74 patients from Russia, 89.2% patients (n = 66) were bionaive. The paper presents the results of bionaive patients. Sixty-six are included in the induction phase: 18 received ustekinumab 130 mg IV, 25 received ustekinumab 6 mg/kg IV, and 23 received a placebo. At week 8 in the groups of patients treated with ustekinumab at doses of 6 mg/kg and 130 mg, clinical remission was achieved in 24.0% and 16.7%, respectively, in the placebo group, the rate was 17.4%. The proportion of patients with clinical responses at week 8 was 68.0%, 50.0% and 39.1% in the ustekinumab 6 mg/kg, 130 mg and placebo groups, respectively. Mucosal healing at week 8 was achieved in 48.0% in the ustekinumab 6 mg/kg group, in 33.3% of patients in the ustekinumab 130 mg group, and in 21.7% of patients in the placebo group. Histoendoscopic mucosal healing at week 8 developed in 27.8% of patients in the ustekinumab 130 mg group, in 24.0% of patients in the ustekinumab 6 mg/kg group, and in 21.7% of patients in the placebo group. Forty bionaive patients were re-randomized for further participation in the maintenance phase: 13 patients received ustekinumab 90 mg subcutaneously every 12 weeks, 12 received ustekinumab every 8 weeks, and 15 received a placebo. At week 44, clinical remission was achieved in 46.2% of ustekinumab every 12 weeks, 75.0% of ustekinumab every 8 weeks (p = 0.054 compared with placebo), and 33.3% of placebo. Mucosal healing achieved in 46.2% of patients in the ustekinumab once every 12 weeks group, in 75.0% of patients in the ustekinumab once every 8 weeks group (p = 0.054 compared with. placebo), and in 33.3% of patients in the placebo group. Histoendoscopic mucosal healing achieved in 46.2% of patients in the ustekinumab once every 12 weeks group, while in the ustekinumab once every 8 weeks group, the percentage of such patients was 75.0% (p = 0.021 compared with placebo) and in the placebo group — 26.7%. Symptomatic remission at week 152 developed in 83.3% in the ustekinumab every 12 weeks group, 81.8% in the ustekinumab every 8 weeks group. In the induction phase decrease of CRP and FCP median levels detected in patients treated with ustekinumab, in the maintenance phase, median levels of laboratory inflammatory markers after induction were sustained by ustekinumab treatment. The rate of steroid-free symptomatic remission at week 152 was consistent with the rate of symptomatic remission. The safety profile of ustekinumab was generally consistent with placebo during all follow up period. CONCLUSION : subanalysis confirmed shortand long-term efficacy and safety in Russian patients with moderate to severe active ulcerative colitis. The results of subanalysis are consistent with previously obtained data in the population of patients participating in the global UNIFI program.

Background: Clearance of tau seeds by immunization with tau antibodies is currently evaluated as therapeutic strategy to block the spreading of tau pathology in Alzheimer’s disease and other tauopathies. Preclinical evaluation of passive immunotherapy is performed in different cellular culture systems and in wild-type and human tau transgenic mouse models. Depending on the preclinical model used, tau seeds or induced aggregates can either be of mouse, human or mixed origin. Objective: We aimed to develop human and mouse tau-specific antibodies to discriminate between the endogenous tau and the introduced form in preclinical models. Methods: Using hybridoma technology, we developed human and mouse tau-specific antibodies that were then used to develop several assays to specifically detect mouse tau. Results: Four antibodies, mTau3, mTau5, mTau8, and mTau9, with a high degree of specificity for mouse tau were identified. Additionally, their potential application in highly sensitive immunoassays to measure tau in mouse brain homogenate and cerebrospinal fluid is illustrated, as well as their application for specific endogenous mouse tau aggregation detection. Conclusion: The antibodies reported here can be very important tools to better interpret the results obtained from different model systems as well as to study the role of endogenous tau in tau aggregation and pathology observed in the diverse mouse models available.

We consider nonparametrically estimating the joint distribution of a survival time and mark variable, where the survival time is subject to right censoring and the mark variable is only observed when the survival time is not censored. The possibility of dependent censoring is allowed for using inverse probability of censoring weights. The proposed estimator is shown to be consistent and asymptotically normal. Finite sample behavior of the proposed methods are investigated via simulation study. Finally, we illustrate the nonparametric estimator from a recent HIV vaccine efficacy trial.

Background and aims: Tesnatilimab, a monoclonal antibody targeting NKG2D, was evaluated in Crohn's disease (CD) patients who had failed or were intolerant to biologic or conventional therapy. Methods: TRIDENT was a phase 2b, 2-part, randomized, double-blind, placebo-controlled, parallel-arm, multicenter study. In Part 1 (proof of concept), 145 patients who were biologic intolerant or refractory (Bio-IR) or had not failed biologic therapy (Bio-NF) were randomized in a 1:1 ratio to placebo subcutaneous (SC) or tesnatilimab 400 mg SC. In Part 2 (dose ranging), 243 Bio-IR and Bio-NF patients were randomized in a 1:1:1:1:1 ratio to placebo, tesnatilimab (50 mg, 150 mg, 400 mg), or intravenous infusion of ustekinumab ~6 mg/kg at Week 0 and 90 mg SC at Weeks 8 and 16. The primary endpoint was mean change from baseline in Crohn's Disease Activity Index (CDAI) at Week 8 (Part 1) and Week 12 (Part 2). Clinical and endoscopic remission/response were evaluated. Efficacy analyses were also assessed by NKG2D and MICB single-nucleotide polymorphism (SNP) status (SNP-positive means positive in at least 1 of 2 SNPs). Safety events were summarized. Results: In Part 1, mean change from baseline in CDAI score was significantly greater with tesnatilimab vs placebo at Week 8 (-103.6 vs -60.0; p<0.01). In Part 2, no dose-response signal was detected. Mean changes from baseline in CDAI at Week 12 were -93.2, -72.2, and -84.3 for low, middle, high dose, respectively, vs -59.2 for placebo and -148.8 for ustekinumab. Similar reductions from baseline in CDAI score were observed in patients with tesnatilimab, regardless of SNP status. Clinical remission rates were greater with tesnatilimab than placebo in Parts 1 and 2, while endoscopic response rates were greater with tesnatilimab only in Part 1. No unexpected safety events occurred. Conclusions: Tesnatilimab was well tolerated. The efficacy of tesnatilimab in patients with CD was significant for the primary endpoint in Part 1; however, no dose-response signal was detected for the primary endpoint in Part 2. Based on these inconsistent findings, tesnatilimab was not considered an effective treatment for patients with CD and no further development is planned.

Background: The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma, are not well understood. We investigated whether ambient levels of fine PM with aerodynamic diameter ≤2.5 microns (PM2.5 ) are associated with alterations in circulating monocytes in children with or without asthma. Methods: Monocyte phenotyping was performed by cytometry time-of-flight (CyTOF). Cytokines were measured using cytomtric bead array and Luminex assay. ChIP-Seq was utilized to address histone modifications in monocytes. Results: Increased exposure to ambient PM2.5 was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by the upregulation of proinflammatory mediators, such as TNF, IL-6, and IL-8, upon stimulation with house dust mite or lipopolysaccharide. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes. Conclusion: The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution-induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution.

Since the original outbreak of the SARS-CoV-2 virus, several rapidly spreading SARS-CoV-2 variants of concern (VOC) have emerged. Here, we show that a single dose of Ad26.COV2.S (based on the Wuhan-Hu-1 spike variant) protects against the Gamma and Delta variants in naive hamsters, supporting the observed maintained vaccine efficacy in humans against these VOC. Adapted spike-based booster vaccines targeting Omicron variants have now been authorized in the absence of human efficacy data. We evaluated the immunogenicity and efficacy of Ad26.COV2.S.529 (encoding a stabilized Omicron BA.1 spike) in naive mice and in hamsters with pre-existing immunity to the Wuhan-Hu-1 spike. In naive mice, Ad26.COV2.S.529 elicited higher neutralizing antibody titers against SARS-CoV-2 Omicron BA.1 and BA.2, compared with Ad26.COV2.S. However, neutralizing titers against the SARS-CoV-2 B.1 (D614G) and Delta variants were lower after primary vaccination with Ad26.COV2.S.529 compared with Ad26.COV2.S. In contrast, we found comparable Omicron BA.1 and BA.2 neutralizing titers in hamsters with pre-existing Wuhan-Hu-1 spike immunity after vaccination with Ad26.COV2.S, Ad26.COV2.S.529 or a combination of the two vaccines. Moreover, all three vaccine modalities induced equivalent protection against Omicron BA.2 challenge in these animals. Overall, our data suggest that an Omicron BA.1-based booster in rodents does not improve immunogenicity and efficacy against Omicron BA.2 over an Ad26.COV2.S booster in a setting of pre-existing immunity to SARS-CoV-2.

Dengue is a major health threat and the number of symptomatic infections caused by the four dengue serotypes is estimated to be 96 million¹ with annually around 10,000 deaths². However, no antiviral drugs are available for the treatment or prophylaxis of dengue. We recently described the interaction between non-structural proteins NS3 and NS4B as a promising target for the development of pan-serotype dengue virus (DENV) inhibitors³. Here we present JNJ-1802—a highly potent DENV inhibitor that blocks the NS3–NS4B interaction within the viral replication complex. JNJ-1802 exerts picomolar to low nanomolar in vitro antiviral activity, a high barrier to resistance and potent in vivo efficacy in mice against infection with any of the four DENV serotypes. Finally, we demonstrate that the small-molecule inhibitor JNJ-1802 is highly effective against viral infection with DENV-1 or DENV-2 in non-human primates. JNJ-1802 has successfully completed a phase I first-in-human clinical study in healthy volunteers and was found to be safe and well tolerated⁴. These findings support the further clinical development of JNJ-1802, a first-in-class antiviral agent against dengue, which is now progressing in clinical studies for the prevention and treatment of dengue.

Background and aims: Non-alcoholic steatohepatitis (NASH) constitutes a significant unmet medical need with a burgeoning field of clinical research and drug development. Platform trials (PT) might help accelerate drug development while lowering overall costs and creating a more patient-centric environment. This review provides a comprehensive and nuanced assessment of the NASH clinical development landscape. Methods: Narrative review and expert opinion with insight gained during the EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. Results: Although NASH represents an opportunity to use adaptive trial designs, including master protocols for PT, there are barriers that might be encountered owing to distinct and sometimes opposing priorities held by these stakeholders and potential ways to overcome them. The following aspects are critical for the feasibility of a future PT in NASH: readiness of the drug pipeline, mainly from large drug companies, while there is not yet an FDA/EMA-approved treatment; the most suitable design (trial Phase and type of population, e.g., Phase 2b for non-cirrhotic NASH patients); the operational requirements such as the scope of the clinical network, the use of concurrent versus non-concurrent control arms, or the re-allocation of participants upon trial adaptations; the methodological appraisal (i.e. Bayesian vs. frequentist approach); patients' needs and patient-centred outcomes; main regulatory considerations and the funding and sustainability scenarios. Conclusions: PT represent a promising avenue in NASH but there are a number of conundrums that need addressing. It is likely that before a global NASH PT becomes a reality, 'proof-of-platform' at a smaller scale needs to be provided.

Background: Studies are available on physician burnout and job satisfaction (JS) in relation to the specific income structure of the country of residence. However, no studies exist that investigate burnout of immigrated physicians taking into account the income structure of their country of origin (IS-COO) as well as duration of immigration. Objective: To determine the influence of IS-COO on JS, income satisfaction, and critical burnout thresholds in the domains of emotional exhaustion (EE), depersonalization (DP) and reduction in personal accomplishment (RPA) among urologists with a migrant background working at German hospitals. Methods: A questionnaire (Survey-Monkey ®/101-items) was conducted among urologists of German hospitals with a migrant background. The online questionnaire was open for study participation from 1 August to 31 October 2020. The study included all physicians with a migration background who were born in a country other than Germany and were currently employed in a German department of urology. Physician burnout (Maslach-Burnout-Inventory) and JS were assessed using validated instruments. The influence of IS-COO and different covariates on the designated endpoints was tested using multivariate-models. Results: 96 urologists with a median stay in Germany of 7 years participated and were stratified according to low (LIC/41.7%), middle (MIC/36.5%) and high (HIC/21.9%) income based on IS-COO. No significant influence of IS-COO on critical thresholds in each burnout domain could be found. Of urologists from LIC, MIC and HIC, 42%, 59% and 57%, respectively, showed rather or extreme JS (p = .446). There was also no significant difference between groups in income satisfaction (p = .838). However, in multivariate-models, duration of stay in Germany (≥7 vs. <7 years) had significant effects on DP (OR: 0.28, p = .038) and RPA (OR: 0.09, p = .014), but not on EE and JS. Conclusion: IS-COO has no impact on burnout and JS among urologists who immigrated to Germany. Similarly, income satisfaction in the country of residence is not influenced by IS-COO.

Objective: Previous analyses of pooled DISCOVER-1 and DISCOVER-2 data through Week 24 showed significantly higher rates of dactylitis resolution in patients treated with guselkumab compared with placebo. Here, we investigate associations between dactylitis resolution and other outcomes through 1 year. Methods: Patients were randomized 1:1:1 to receive subcutaneous injections of guselkumab 100 mg at Week 0, Week 4, and then every 4 or 8 weeks, or placebo with crossover to guselkumab at Week 24. Independent assessors determined dactylitis severity score (DSS; 0-3/digit; total = 0-60). Dactylitis resolution (DSS = 0) (prespecified) and at least 20%, at least 50%, and at least 70% DSS improvement from baseline (post hoc) were determined through Week 52 (nonresponder imputation for treatment failure through Week 24 and for missing data through Week 52). ACR50, tender/swollen joints, low disease activity (LDA) as assessed by composite indices, and radiographic progression (DISCOVER-2 only) were assessed in patients with dactylitis versus without dactylitis resolution at Week 24 and Week 52. Results: Patients with dactylitis at baseline (473 of 1118) had more severe joint and skin disease than those without dactylitis (645 of 1118). At Week 52, approximately 75% of guselkumab-randomized patients with dactylitis at baseline had complete resolution; approximately 80% had at least 70% DSS improvement. Through Week 52, new-onset dactylitis (DSS ≥1) was uncommon among patients with a DSS of 0 at baseline. Guselkumab-randomized patients with dactylitis resolution were more likely to achieve ACR50, at least 50% reduction in tender and swollen joints, and LDA at Week 24 and Week 52 than those without resolution. At Week 52, patients with dactylitis resolution had numerically less radiographic progression from baseline (DISCOVER-2). Conclusion: Through 1 year, approximately 75% of guselkumab-randomized patients had complete resolution of dactylitis; patients exhibiting resolution were more likely to achieve other important clinical outcomes. Given the high burden of dactylitis, resolution may be associated with better long-term patient outcomes.

Subcutaneous daratumumab plus bortezomib/cyclophosphamide/dexamethasone (VCd; D-VCd) improved outcomes versus VCd for patients with newly diagnosed immunoglobulin light-chain (AL) amyloidosis in the phase 3 ANDROMEDA study. We report a subgroup analysis of Asian patients (Japan; Korea; China) from ANDROMEDA. Among 388 randomized patients, 60 were Asian (D-VCd, n = 29; VCd, n = 31). At a median follow-up of 11.4 months, the overall hematologic complete response rate was higher for D-VCd versus VCd (58.6% vs. 9.7%; odds ratio, 13.2; 95% confidence interval [CI], 3.3–53.7; P < 0.0001). Six-month cardiac and renal response rates were higher with D-VCd versus VCd (cardiac, 46.7% vs. 4.8%; P = 0.0036; renal, 57.1% vs. 37.5%; P = 0.4684). Major organ deterioration progression-free survival (MOD-PFS) and major organ deterioration event-free survival (MOD-EFS) were improved with D-VCd versus VCd (MOD-PFS: hazard ratio [HR], 0.21; 95% CI, 0.06–0.75; P = 0.0079; MOD-EFS: HR, 0.16; 95% CI, 0.05–0.54; P = 0.0007). Twelve deaths occurred (D-VCd, n = 3; VCd, n = 9). Twenty-two patients had baseline serologies indicating prior hepatitis B virus (HBV) exposure; no patient experienced HBV reactivation. Although grade 3/4 cytopenia rates were higher than in the global safety population, the safety profile of D-VCd in Asian patients was generally consistent with the global study population, regardless of body weight. These results support D-VCd use in Asian patients with newly diagnosed AL amyloidosis. ClinicalTrials.gov Identifier: NCT03201965.

Much of the human proteome is involved in mRNA homeostasis, but most RNA-binding proteins lack chemical probes. Here we identify electrophilic small molecules that rapidly and stereoselectively decrease the expression of transcripts encoding the androgen receptor and its splice variants in prostate cancer cells. We show by chemical proteomics that the compounds engage C145 of the RNA-binding protein NONO. Broader profiling revealed that covalent NONO ligands suppress an array of cancer-relevant genes and impair cancer cell proliferation. Surprisingly, these effects were not observed in cells genetically disrupted for NONO, which were instead resistant to NONO ligands. Reintroduction of wild-type NONO, but not a C145S mutant, restored ligand sensitivity in NONO-disrupted cells. The ligands promoted NONO accumulation in nuclear foci and stabilized NONO–RNA interactions, supporting a trapping mechanism that may prevent compensatory action of paralog proteins PSPC1 and SFPQ. These findings show that NONO can be co-opted by covalent small molecules to suppress protumorigenic transcriptional networks.

Background: Cardiovascular conditions are the most prevalent comorbidity among patients with prostate cancer, regardless of treatment. Additionally, cardiovascular risk has been shown to increase following exposure to certain treatments for advanced prostate cancer. There is conflicting evidence on risk of overall and specific cardiovascular outcomes among men treated for metastatic castrate resistant prostate cancer (CRPC). We, therefore, sought to compare incidence of serious cardiovascular events among CRPC patients treated with abiraterone acetate plus predniso(lo)ne (AAP) and enzalutamide (ENZ), the two most widely used CRPC therapies. Methods: Using US administrative claims data, we selected CRPC patients newly exposed to either treatment after August 31, 2012, with prior androgen deprivation therapy (ADT). We assessed incidence of hospitalization for heart failure (HHF), ischemic stroke, and acute myocardial infarction (AMI) during the period 30-days after AAP or ENZ initiation to discontinuation, outcome occurrence, death, or disenrollment. We matched treatment groups on propensity-scores (PSs) to control for observed confounding to estimate the average treatment effect among the treated (AAP) using conditional Cox proportional hazards models. To account for residual bias, we calibrated our estimates against a distribution of effect estimates from 124 negative-control outcomes. Results: The HHF analysis included 2322 (45.1%) AAP initiators and 2827 (54.9%) ENZ initiators. In this analysis, the median follow-up times among AAP and ENZ initiators (after PS matching) were 144 and 122 days, respectively. The empirically calibrated hazard ratio (HR) estimate for HHF was 2.56 (95% confidence interval [CI]: 1.32, 4.94). Corresponding HRs for AMI and ischemic stroke were 1.94 (95% CI: 0.90, 4.18) and 1.25 (95% CI: 0.54, 2.85), respectively. Conclusions: Our study sought to quantify risk of HHF, AMI and ischemic stroke among CRPC patients initiating AAP relative to ENZ within a national administrative claims database. Increased risk for HHF among AAP compared to ENZ users was observed. The difference in myocardial infarction did not attain statistical significance after controlling for residual bias, and no differences were noted in ischemic stroke between the two treatments. These findings confirm labeled warnings and precautions for AAP for HHF and contribute to the comparative real-world evidence on AAP relative to ENZ.

Medication nonadherence in schizophrenia can have serious implications including relapses and hospitalization. Long-acting injectable (LAI) antipsychotics require fewer administrations, while ensuring sustained medication coverage. In this review, we summarize the expected real-world benefits of longer dosing intervals in the management of schizophrenia. LAIs are associated with improved clinical outcomes of less frequent relapses and reduced functional impairment, encouraging patients to regain control of their lives. Aripiprazole lauroxil and paliperidone palmitate three-monthly (PP3M) LAIs have longer dosing intervals of 2-3 months and provide improved outcomes in patients with schizophrenia. Paliperidone palmitate six-monthly (PP6M) LAI provides the longest dosing interval, twice-yearly dosing, among existing LAIs. Decreasing the frequency of LAI administrations has the potential to reduce occurrence of serious outcomes associated with poor medication adherence. By eliminating the need for daily oral antipsychotic dosing, LAIs could increase the likelihood of patient acceptance, decrease stigma, and promote self-esteem. Longer intervals of medication coverage may be desirable for patients with higher risk of relapse including adults with recent-onset schizophrenia, those living in circumstances that may deprive them of regular access (eg, homeless), those that are in transitions between care settings or to reduce interpersonal contact during public health emergencies (eg, COVID-19 pandemic).

JNJ-10450232 (NTM-006), a novel non-opioid, non-nonsteroidal anti-inflammatory drug with structural similarities to acetaminophen, demonstrated anti-pyretic and/or analgesic activities in preclinical models and humans and reduced potential to cause hepatotoxicity in preclinical species. Metabolism and disposition of JNJ-10450232 (NTM-006) following oral administration to rats, dogs, monkeys and humans are reported. Urinary excretion was the major route of elimination based on recovery of 88.6% (rats) and 73.7% (dogs) of oral dose. The compound was extensively metabolized based on low recovery of unchanged drug in excreta from rats (11.3%) and dogs (18.4%). Clearance is driven by O-glucuronidation, amide hydrolysis, O-sulfation and methyl oxidation pathways. The combination of metabolic pathways driving clearance in human is covered in at least one preclinical species despite a few species-dependent pathways. O-Glucuronidation was the major primary metabolic pathway of JNJ-10450232 (NTM-006) in dogs, monkeys and humans, although amide hydrolysis was another major primary metabolic pathway in rats and dogs. A minor bioactivation pathway to quinone-imine is observed only in monkeys and humans. Unchanged drug was the major circulatory component in all species investigated. Except for metabolic pathways unique to the 5-methyl-1H-pyrazole-3-carboxamide moiety, metabolism and disposition of JNJ-10450232 (NTM-006) are similar to acetaminophen across species.

Golimumab was recently evaluated in a Phase 2a, randomized, double-blind, placebo-controlled, multicenter study for safety and efficacy in children and young adults with newly diagnosed T1D (type 1 diabetes). Golimumab showed significant treatment effect where endogenous insulin production was preserved and clinical and metabolic parameters improved. The objective of this report was to evaluate pharmacokinetic (PK) and pharmacodynamic (PD) data from the T1GER study by developing a population pharmacokinetic (PopPK) model and performing exposure-response (ER) analyses. The PopPK model was developed using data from the T1D study and two other pediatric studies with golimumab in ulcerative colitis and in polyarticular juvenile idiopathic arthritis. A one-compartment model with first-order absorption and elimination was applied to describe the concentration-time profiles. Typical parameters normalized to the values in subjects with a standard weight of 70 kg were: apparent clearance (CL/F), 0.850 L/day; apparent volume of distribution (V/F), 16.0 L; absorption rate constant (ka ), 1.01 day-1 . From the ER analyses, no clear trends were observed for changes in both C-peptide AUC and HbA1c levels for the relatively narrow exposure ranges following the body surface area-based dosing regimen used in this study. In conclusion, the developed PopPK model was able to adequately describe the observed PK of golimumab in T1D patients. Although golimumab showed significant treatment effect, the ER analyses did not show clear trends within the active treatment group which may indicate that the exposure from this T1D-specific dosing regimen was at the plateau of the ER curve. This article is protected by copyright. All rights reserved.