Intravenous Golimumab in Children With Polyarticular-Course Juvenile Idiopathic Arthritis: Long-Term Extension of an Open-Label Phase III Study.

OBJECTIVE: To report pharmacokinetics (PK), immunogenicity, clinical effect, and safety of intravenous (IV) golimumab in children with active polyarticular-course juvenile idiopathic arthritis (pcJIA) who participated in A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy (GO-VIVA)'s open-label, long-term extension (LTE) through week 252. METHODS: GO-VIVA participants who continued IV golimumab (80 mg/m2 every 8 weeks) after week 52 were included. PK and safety were assessed through week 244 (last dose) and week 252, respectively, and clinical response through week 116. Clinical outcomes included JIA-American College of Rheumatology (ACR) responses and clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10). Binary outcomes used nonresponder imputation, and other descriptive analyses used observed data. RESULTS: Of 112/127 (88.2%) participants entering the LTE, 69 completed the week 252 visit. Median steady-state trough golimumab concentrations were generally maintained from week 52 through week 244 (range 0.3-0.6 µg/mL). Antigolimumab antibody rates were consistent through week 52 (39.2% [49/125]) and week 244 (44.8% [56/125]). Week 52 JIA-ACR 30/50/70/90 response rates (75.6% [96/127], 74% [94/127], 65.4% [83/127], and 48.8% [62/127], respectively) were generally maintained through week 116 (72.4% [92/127], 71.7% [91/127], 63.8% [81/127], and 50.4% [64/127], respectively), when the median cJADAS10 was 1.6 and 56.7% (72/127) of participants achieved cJADAS10 ≤ 5 (minimal disease activity). Rates (per 100 patient-years) of serious adverse events and serious infections through week 252 were 7.7 and 3.9, respectively. CONCLUSION: GO-VIVA LTE participants experienced adequate PK exposure and stable safety and immunogenicity. The majority of participants experienced no more than minimal residual disease activity. Data suggest IV golimumab treatment provided durable clinical response through week 116, with an acceptable risk-benefit profile.

Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Pregnancy and Infant Outcomes After Prenatal Exposure to Golimumab in Denmark, Finland, and Sweden 2006-2019.

PURPOSE: To present the main findings of a post-authorization safety study assessing pregnancy and infant outcomes after prenatal golimumab exposure in a real-world setting. METHODS: This observational population-based cohort study included data from pregnancies ending in 2006-2018 (Finland) or 2019 (Denmark, Sweden). Infants born to women with rheumatic diseases or ulcerative colitis diagnoses were identified. Based on prescription fills from 90 days prior to pregnancy until delivery, infants were assigned to one of the four drug-exposure cohorts: golimumab, other anti-TNF biologics, other biologics, and nonbiologic systemic therapy, and the general population. Prevalence of adverse pregnancy outcomes, mortality, diagnoses of major congenital anomalies (MCA), and inpatient infections in the infants' first year of life were assessed. Odds ratios and 95% CIs were calculated for MCA and infection. RESULTS: Among 134 infants in the golimumab cohort, none were stillborn or died in the first year of life. MCA were diagnosed in 4.5% of the infants in the golimumab cohort, versus 6.8%, 10.9%, 5.5%, and 4.6% in the other anti-TNF biologics, other biologics, nonbiologic systemic therapy and general population cohorts, respectively. Inpatient infections were diagnosed in 11% of golimumab-exposed infants, compared with 9%-11% of infants in the other cohorts. Unadjusted and selected adjusted comparisons showed no association between prenatal golimumab exposure and MCA or infection compared with the other exposure cohorts or general population. CONCLUSIONS: The number of infants with prenatal golimumab exposure was low, but results are reassuringly consistent with the evidence available for other anti-TNF biologics. Continued monitoring is needed.

Efficacy of golimumab in rheumatoid arthritis patients at high risk of a poor prognosis: Post hoc analysis of GO-FORTH study using cluster analysis.

OBJECTIVES: Our objective was to assess the efficacy of golimumab (GLM) in patients with poor prognostic factors (PPFs). METHODS: This is a post hoc analysis of GO-FORTH Phase 2/3 study. Cluster analysis was used to determine a patient population with high-risk patterns based on seven PPFs suggested by the European Alliance of Associations for Rheumatology recommendations and limited physical function. Radiographic progression, disease activity, and physical function and associated factors were evaluated over 52 weeks. RESULTS: Overall, 261 rheumatoid arthritis patients were classified into three clusters characterised by high disease activity, high C-reactive protein levels, and limited physical function at baseline. GLM showed suppression of progressive modified total sharp score and decreases in Disease Activity Score 28-joint counts with erythrocyte sedimentation rate and Health Assessment Questionnaire - Disease Index, in all the clusters. In Cluster C that showed almost all the PPF characteristics, a higher rate of change in modified total sharp score ≤0 was observed in GLM 100 mg group than in GLM 50 mg group (63.9% versus 46.5%). C-reactive protein concentration and physical limitation were associated with radiographic progression of Cluster C in GLM treatment. CONCLUSIONS: GLM was effective in rheumatoid arthritis patients in a subpopulation at high risk of PPF in GO-FORTH study. A dose of 100 mg may be more beneficial in preventing radiographic progression in this population.

Efficacy and safety of golimumab in patients with non-radiographic axial spondyloarthritis: a withdrawal and retreatment study (GO-BACK).

OBJECTIVES: The GO-BACK study was designed to evaluate the efficacy and safety of golimumab (GLM) treatment withdrawal in adults with non-radiographic axial spondyloarthritis (nr-axSpA) who demonstrate inactive disease during a 10-month open-label (OL) GLM run-in. METHODS: Eligible participants received OL GLM in period 1. In period 2, participants who achieved inactive disease were randomized 1:1:1 to receive double-blind (DB) treatment with monthly placebo (PBO, treatment withdrawal) or continued GLM treatment given monthly (GLM QMT) or every 2 months (GLM Q2MT). Participants who did not have a disease flare continued DB treatment for ∼12 months. Participants with a disease flare discontinued DB treatment and resumed monthly OL GLM. Primary endpoint compared the proportion of participants without a disease flare in the continued GLM treatment groups (QMT or Q2MT) vs PBO in a multiplicity-controlled, step-down fashion. Safety follow-up continued for ∼3 months after last treatment. RESULTS: A total of 188 patients, out of the 323 enrolled, were eligible for participation in period 2. Both GLM QMT and GLM Q2MT were superior to treatment withdrawal (PBO) in preventing disease flare (P < 0.001), with a treatment-difference vs PBO of 50.4% and 34.4% for the GLM QMT and GLM Q2MT groups, respectively. The time-to-first flare was significantly longer (log-rank P < 0.0001) with GLM treatment compared with PBO. Of 53 participants (in Q2MT or PBO) who had a confirmed disease flare, 51 (96.2%) attained a clinical response within 3 months of restarting OL GLM. Adverse events were consistent with the known GLM safety profile. CONCLUSION: Among participants with active nr-axSpA who attained inactive disease after 10 months of GLM treatment, continued GLM treatment is well tolerated and provides superior protection against disease flares compared with GLM withdrawal. (EudraCT: 2015-004020-65, registered on 30 March 2022; NCT: 03253796, registered on 18 August 2017.).

Early MOnitoring of REsponse (MORE) to Golimumab Therapy: Results of a Multicentre, Prospective Observational Trial.

BACKGROUND: The therapeutic goal of clinical remission in patients with moderate to severe ulcerative colitis (UC) is achieved after biological therapy only in 16-39%. Individualization of therapeutic intervention would benefit from prediction of early response. STUDY OBJECTIVE: The primary objective of our study was to assess golimumab (GLM) trough serum level of ≥2.5 µg/mL in combination with a reduction of faecal calprotectin (FC) of ≥50% at week 6 compared to baseline to predict clinical response at week 26 after regular GLM intake. METHODS: Patients with moderate to severe active UC and planned GLM treatment were recruited for a prospective, multicentre, observational study in Germany. Prediction of clinical response was assessed by FC and GLM trough level. Missing data were imputed as therapy failure according to the last observation carried forward method. RESULTS: Fifty nine patients have been enrolled. 54% of patients were anti-TNF naïve. Clinical response at week 6 was a significant predictor for achieving clinical response at week 26 (odds ratio [OR] 10.97, confidence interval [CI], 2.96-40.68; p < 0.001). Moreover, patients with a GLM trough level of ≥2.5 µg/mL and a ≥50% reduction of FC at week 6 had an OR of 5.33 (95% CI, 0.59-47.84) to achieve clinical response at week 26. CONCLUSION: Clinical response at week 6 is the best predictive marker for achieving clinical response at week 26. Consideration of significant reduction of FC and trough GLM serum levels could improve prediction of response.

Incident psoriasis under treatment with tumor necrosis factor-α inhibitors in juvenile idiopathic arthritis patients-analysis of the BiKeR registry.

The efficacy of tumor necrosis factor inhibitors (TNFi) for the treatment of psoriasis is well established, but patients may develop psoriasis for the first time while on TNFi as a paradoxical effect. Limited data on this association in patients with juvenile idiopathic arthritis (JIA) are available. Safety data from patients registered to the German Biologics registry (BiKeR) were analyzed. Patients were grouped by treatment regime: single TNFi, multiple TNFi, non-TNFi biologics or bDMARD-naïve control group receiving methotrexate. TNFi-associated psoriasis was defined as incident diagnosis of psoriasis after starting TNFi treatment. Patients with a history of psoriasis or psoriasis arthritis prior to TNFi therapy were excluded. Event rates using AEs reported after first dose were compared by Wald's test. A total of 4149 patients were treated with a TNFi (etanercept, adalimumab, golimumab, infliximab), 676 with a non-TNFi biologic (tocilizumab, abatacept, anakinra, canakinumab) and 1692 with methotrexate only. A total of 31 patients were diagnosed with incident psoriasis while on one of the above treatments. Compared with methotrexate, psoriasis was more frequent in the TNFi cohorts (RR 10.8, p = 0.019), specifically in the subgroup of TNF antibodies (RR 29.8, p = 0.0009), whereas no significant signal was observed with etanercept. Also, non-TNFi-treated patients presented high incident psoriasis rates (RR 25.0, p = 0.003). Our findings indicate a higher rate of incident psoriasis in JIA patients treated with TNFi monoclonal antibodies or non-TNFi biologic treatment. JIA patients receiving monoclonal antibody TNFi or non-TNFi bDMARD should be monitored for incident psoriasis. Medication change, if topical skin treatment remains insufficient, may be considered.

Real-world effectiveness of golimumab in adult patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis and an inadequate response to initial TNFi therapy in Greece: the GO-BEYOND prospective, observational study.

The impact of golimumab (GLM) on remission or low disease activity (LDA) was evaluated in patients with moderate-to-severe rheumatoid arthritis (RA), progressive psoriatic arthritis (PsA), or severe axial spondyloarthritis (axSpA), who failed previous treatment for their rheumatic disease with one initial tumor necrosis factor α inhibitor (TNFi). This is a multicenter, prospective, real-world observational 18-month study, conducted in Greece. The primary endpoint, assessed at 6 months, included the proportion of patients attaining LDA and/or remission (Disease Activity Score for 28 joints based on C-reactive protein [DAS28-CRP] ≤ 3.2), minimal disease activity (MDA; MDA criteria), and moderate disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] score 4-7), respectively. Other endpoints evaluated the persistence to GLM treatment and its impact on patients' work productivity (Work Productivity and Activity Impairment [WPAI] instrument) and quality of life (QoL; EuroQoL5 dimensions 3 levels [EQ-5D-3L] questionnaire). Descriptive statistics, the Wilcoxon signed-rank test, and Kaplan-Meier method were used for analyses. At 6 months, LDA was achieved by 46.4% of patients with RA, MDA by 57.1% of patients with PsA, and BASDAI 4-7 by 24.1% of patients with axSpA. For all study patients, persistence rates on GLM were high (85.1-93.7%) over 18 months; all WPAI domain scores and the EQ-5D-3L index score improved significantly (p < 0.001) from baseline to 18 months. GLM treatment was effective in patients with RA, PsA, or axSpA who had failed previous treatment with one TNFi and led to significant WPAI and QoL improvements. Persistence rates were high. Trial registration number and date of registration: As per the local regulations the study has been registered at the national registry for non-interventional studies https://www.dilon.sfee.gr/studiesp_d.php?meleti_id=MK8259-6995 .

Rituximab as possible therapy in TNF inhibitor-induced IgA vasculitis with severe renal involvement.

BACKGROUND: We observe the increasing use of tumor necrosis factor (TNF) inhibitors in patients affected by chronic inflammatory diseases. These drugs provide good control of symptoms, contributing to significant improvement in the quality of life in individuals with high disease burden. On the other hand, along with their wider use and longer follow-up periods the number of reports regarding their adverse effects is also increasing. The reported complications include drug-induced vasculitis with possible kidney involvement. In the literature we can distinguish more frequently described ANCA-associated vasculitis and more rarely occurring immunoglobulin A vasculitis. Although uncommon, such complications may present with potentially life-threatening vital organ dysfunction; therefore, adequate monitoring and effective therapy are necessary. CASE PRESENTATION: We report two cases of TNF inhibitor-induced vasculitis with severe acute worsening of renal function and significant proteinuria. The first patient was receiving golimumab therapy for ankylosing spondylitis and the second patient was treated with adalimumab for psoriasis and psoriatic arthritis. In the second case dialysis treatment was necessary and the patient presented recurrence of vasculitis after rechallenge with adalimumab. Both patients underwent renal biopsy which showed findings compatible with drug-induced IgA vasculitis and both were treated successfully with corticosteroids and rituximab. CONCLUSIONS: To the best of our knowledge this is the first report of rituximab use in drug-induced IgA vasculitis with renal involvement. Combination of corticosteroids and rituximab can be an effective therapy in case of vasculitis with kidney failure and a preferable option for selected patients with drug-induced IgA vasculitis compared to cyclophosphamide. More studies are necessary to establish suitable short- and long-term treatment. Given the rarity of this disorder, case reports and case series can provide practical guidance until additional studies become available.

Focus on Anti-Tumour Necrosis Factor (TNF)-α-Related Autoimmune Diseases.

Anti-tumour necrosis factor (TNF)-α agents have been increasingly used to treat patients affected by inflammatory bowel disease and dermatological and rheumatologic inflammatory disorders. However, the widening use of biologics is related to a new class of adverse events called paradoxical reactions. Its pathogenesis remains unclear, but it is suggested that cytokine remodulation in predisposed individuals can lead to the inflammatory process. Here, we dissect the clinical aspects and overall outcomes of autoimmune diseases caused by anti-TNF-α therapies.

Long-term tolerability and efficacy of golimumab in active non-radiographic axial spondyloarthritis: results from open-label extension.

OBJECTIVES: We report the open-label extension (OLE) of the GO-AHEAD study evaluating the long-term efficacy and safety of golimumab (GLM) in patients with non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: Patients [both GLM- and placebo (PBO)-treated in the double-blind phase] received GLM 50 mg every 4 weeks during the OLE (36-week treatment; additional 8-week safety follow-up; GLM/GLM and PBO/GLM groups). All patients who entered and received ≥1 dose of study treatment in the OLE were included in the efficacy and safety analyses. The primary efficacy evaluations were the proportions of patients achieving 20% and 40% improvement in the ASAS criteria (ASAS20 and ASAS40, respectively). Responders' analyses were calculated using a non-responder imputation approach. RESULTS: Of 198 patients randomised, 189/198 (95.5%) entered the OLE; 174/198 patients (87.9%) completed all visits. Although the proportion of responders increased from week 16 to week 52 in the OLE in both GLM/GLM and PBO/GLM groups, the GLM/GLM group had a higher proportion of responders than the PBO/GLM group throughout the OLE from week 16 to week 52 (ASAS20: 71.1% to 83.9% vs 40.0% to 75.0%, respectively; ASAS40: 56.7% to 76.3% vs 23.0% to 59.4%, respectively; ASAS partial remission: 33.0% to 53.8% and 18.0% to 45.8%). In the OLE, the overall incidence of AEs was lower in the GLM/GLM vs PBO/GLM groups (41.9% and 54.2%). CONCLUSIONS: Sustained improvement in clinical efficacy was observed at 52 weeks in patients with nr-axSpA following GLM treatment. GLM was well tolerated and provided substantial long-term benefits to patients with nr-axSpA. TRIAL REGISTRATION: NCT01453725; United States National Library of Medicine clinical trials database; www.clinicaltrials.gov.

Dose-escalation of adalimumab, golimumab or ustekinumab in inflammatory bowel diseases: characterization and implications in real-life clinical practice.

OBJECTIVES: Dose-escalation is a common practice to optimize treatment with subcutaneously administered biologicals in Crohn's disease (CD) and ulcerative colitis (UC). However, limited data is available on the extent of dose-escalation in real-life. Here, we analyzed treatment persistence, dose-escalation, concomitant corticosteroid use, and costs of adalimumab, golimumab, and ustekinumab in inflammatory bowel diseases (IBD). METHODS: This was a nationwide, retrospective, non-interventional registry study. All adult patients who were diagnosed with CD or UC and had purchased adalimumab, golimumab, or ustekinumab from Finnish pharmacies between 2008 and 2018 were included in the study and followed up for 24 months after treatment initiation. RESULTS: A total of 2884 patients were included in the analyses. For adalimumab, treatment persistence was higher for CD patients compared to UC patients both at months 12 (46.2% versus 37.1%; p < .0001) and 24 (26.1% versus 19.7%; p < 0.0001). For golimumab (UC), treatment persistence was 48.3% at month 12 and 28.1% at month 24. The 12-month treatment persistence rate for patients on ustekinumab (CD) was 47.1%. Cumulative doses exceeding the regular dosing according to the summary of product characteristics (SPC), was observed for adalimumab in CD during the first 6 months of treatment (62.9% of the treatment periods), golimumab in the later stages of the UC treatment (52-54% of treatment periods at months 7-24), and ustekinumab during the first 6 months (70.7%). CONCLUSIONS: Based on this study, dose-escalation of subcutaneously administered biologicals is a common clinical practice in IBD. This has implications for treatment costs, use of concomitant medications, and treatment outcomes.

Combining biological therapies in patients with inflammatory bowel disease: a Finnish multi-centre study.

BACKGROUND AND AIMS: Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study. MATERIALS AND METHODS: Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms. RESULTS: A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn's disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2-31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%). CONCLUSION: DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.

Protective effects of recombinant human golimumab and pentoxifylline in nephrotoxicity induced by cisplatin.

In cisplatin-induced nephrotoxicity, the significant role of activation of inflammatory pathways has been reported earlier. Studies indicate elevated expression and activity of tumor necrosis factor-α (TNF-α) in both, serum and kidneys of cisplatin-treated animals. Golimumab, an anti-TNF biologic, has been approved for the management of many inflammatory conditions. This experiment was planned and executed to evaluate the impact of golimumab on renal function, inflammation in cisplatin-induced nephrotoxicity in mice, and oxidative stress. Cisplatin (22 mg/kg) as a single intraperitoneal injection was used to induce nephrotoxicity in mice. Golimumab was administered at 24 mg/kg for 7 days by subcutaneous route. Pentoxifylline (PTX) was administered for 7 days (150 mg/kg) as a reference standard. Renal functions, oxidative stress, and inflammation were evaluated on the seventh day. Cisplatin administration in mice caused a significant rise in serum cystatin C, creatinine, blood urea nitrogen, and neutrophil gelatinase-associated lipocalin. A significant rise of urinary clusterin, kidney injury molecule-1, and ß-N-acetylglucosaminidase levels was also seen in cisplatin-treated animals. Furthermore, cisplatin-induced nephrotoxicity was associated with a significant increase in oxidative stress and inflammation in serum and kidneys. Golimumab treatment significantly prevented the cisplatin-induced alteration in markers of renal function and renal damage. There was a significant reduction in oxidative stress and inflammation in golimumab-treated animals. Furthermore, the histopathological evaluation also revealed inverted changes in the proximal tubules after golimumab treatment in kidneys after cisplatin toxicity. The standard drug, PTX, also prevented nephrotoxicity caused by cisplatin as indicated by the recovery in renal function, reduction in oxidative stress and inflammation. These results indicate that golimumab was effective in nephrotoxicity induced by cisplatin through inhibition of oxidative stress, and inflammatory response.

Is biologic therapy the future of granuloma annulare treatment?

Granuloma annulare (GA) is a benign inflammatory skin disease that presents with erythematous papules and annular plaques. The pathogenesis of GA remains unknown and may potentially involve type 1 T helper cell (Th1)-mediated delayed-type hypersensitivity reaction. GA is associated with many conditions such as malignancy, trauma, thyroid disease, diabetes mellitus, and viral infection. The role of biological treatment is under investigation. In this article, we present a case of GA development following systemic treatment of psoriatic arthritis in a 59-year-old patient; golimumab therapy resulted in the successful treatment of both psoriatic arthritis and GA. This is the first case report describing GA therapy using golimumab.

Therapeutic Drug Monitoring of Golimumab for the Prediction of Long-Term Clinical Remission in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: A considerable number of patients with ulcerative colitis (UC) who initially respond to golimumab (GLM), an anti-TNF-α antibody, gradually lose clinical response. Therapeutic drug monitoring has been proposed to optimize serum anti-TNF-α antibody concentrations before the loss of response; however, little is known about ideal serum GLM concentrations. We aimed to evaluate whether the serum GLM trough levels (TLs) early after the initiation of induction therapy affect the long-term outcomes in UC and to identify the early GLM TLs that should be targeted for better long-term outcomes. METHODS: Thirty-one patients were prospectively evaluated. The primary outcome was clinical remission at 54 weeks, and we measured the serum GLM TLs at weeks 6, 10, and 14. Receiver operating characteristic (ROC) curves were constructed to identify optimal GLM TL thresholds early after induction therapy that were associated with clinical remission at week 54. RESULTS: The GLM TL at week 14, but not at weeks 6 or 10, was significantly associated with clinical remission at week 54 (median [IQR] 1.6 [1.3-1.6] µg/mL vs. 0.9 [0.6-1.3] µg/mL; p = 0.04). The area under the ROC curve for GLM TLs at week 14 was 0.78. We identified a week-14 GLM TL of 1.1 µg/mL as the target threshold for achieving clinical remission at week 54. CONCLUSION: Our results demonstrate the value of early serum GLM TLs in predicting the long-term outcomes of GLM for patients with UC.

The effects of golimumab on work productivity and quality of life among work-active axial spondyloarthritis and psoriatic arthritis patients treated in the routine care in Greece: the 'GO-UP' study.

PURPOSE: To examine the impact of golimumab, on work productivity, activity limitation, and quality of life (QoL) in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: This real-world, multicenter, prospective study consecutively enrolled adult consented work-active patients with axSpA or PsA, newly initiated on golimumab as per the approved label. Prior receipt of > 1 prior biologic, or switching from another tumor-necrosis factor inhibitor due to primary non-response or safety reasons was not allowed. The Work Productivity and Activity Impairment-Specific Health Problem and the EuroQol 5-Dimensions (EQ-5D)-5-Level instruments were completed by the patients to assess the impact of golimumab on work productivity and activity impairment, and generic QoL, respectively. RESULTS: Overall, 121 eligible patients (mean age: 45.4 years; median disease duration: 11.3 months), 51 diagnosed with PsA and 70 with axSpA, were enrolled by 19 rheumatologists. Over a 11.9-month median observation period, < 1% of injections were missed (as collected by patient diaries), and the 12-month golimumab retention rate was 91.7%. At 3, 6, and 12 months post baseline, in the overall population, work productivity loss improved by a median of 31.4%, 44.2%, and 50.0%; activity impairment improved by 40.0%, 40.0%, and 50.0%; and the EQ-5D UK-weighted utility index improved by 0.24, 0.32, and 0.36 points, respectively (p < 0.001 for all). Statistically significant improvements in these measures were also noted in the PsA and axSpA subpopulations. CONCLUSION: In the routine care in Greece, golimumab displays beneficial effects on work productivity, daily activities, and QoL in work-active patients with axSpA and PsA. TRIAL REGISTRATION: Trial registration number and date of registration: As per the local regulations the study has been registered at the national registry for non-interventional studies https://www.dilon.sfee.gr/studiesp_d.php?meleti_id=MK8259-6083 .

The effects of golimumab on patient centric outcomes amongst rheumatoid arthritis patients in Greece. The GO-Q study.

This study aimed at assessing the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) in real-world settings. GO-Q was an observational, prospective, 12-month study, which recruited patients with moderate-to-severely active RA initiating golimumab treatment per label in rheumatology clinics and private practices. Primary endpoint was the change in PROs [EuroQol-5 Dimensions-3 Levels (EQ-5D-3L) questionnaire, Health Assessment Questionnaire Disease Index (HAQ-DI), and Work Productivity and Activity Index for RA (WPAI:RA)] after 12 months of treatment. Other endpoints included Disease Activity Score for 28 joints with erythrocyte sedimentation rate (DAS28-ESR), healthcare resource utilization, and golimumab adherence. Changes in continuous variables from baseline were evaluated with the paired t test. One hundred forty-five patients were recruited. The mean [standard deviation (SD)] EQ-5D-3L index increased significantly at 12 months versus baseline [from 0.427 (0.206) to 0.801 (0.229); p < 0.0001], with changes as early as 3 and 6 months (both p < 0.0001). Accordingly, there were statistically significant changes in all WPAI:RA domains from baseline to 3, 6, and 12 months (p < 0.0001). Patients' function improved gradually from the third month until the end of follow-up (p < 0.0001 for all time-points). Thirty (27.3%) and 60 (54.6%) patients achieved remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR ≤ 3.2), respectively, at 12 months. Adherence rate to golimumab was high (mean [SD] 90.3% (7.5) at 12 months). In patients with moderate-to-severely active RA, golimumab significantly improved HRQoL, physical function, and work productivity and activity, with improvements in disease activity over 12 months in real-world settings.

The efficacy and safety of TNF inhibitor (golimumab) as salvage treatment in patients with refractory noninfectious uveitis.

BACKGROUND: Tumor necrosis factor inhibitor (TNFi) is recently reported to treat noninfectious uveitis (NIU) effectively. However, as a new kind of TNFi, golimumab is just on the market in China for several years, and its administration for NIU treatment lacks sufficient evidence. Therefore, the current study aimed to investigate the efficacy and safety of golimumab in refractory NIU patients. METHODS: Thirty NIU patients with 49 affected eyes refractory to conventional treatments (corticosteroids and immunosuppressive agents) were consecutively enrolled. They received treatment of TNFi (50 mg golimumab every 4 weeks) for at least 6 months. The anterior chamber cell grade, vitreous haziness grade, central macular thickness, and visual acuity were evaluated at baseline, month (M) 1, M3, and M6. RESULTS: After treatment, the anterior chamber cell grade declined from baseline (0.6 ± 0.7) to M6 (0.3 ± 0.5) (P < 0.001); the vitreous haziness grade decreased from baseline (1.2 ± 1.2) to M6 (0.4 ± 0.5) (P < 0.001); meanwhile, the central macular thickness also reduced from baseline (351.4 ± 90.8 µm) to M6 (271.8 ± 54.4 µm) (P < 0.001). In terms of visual acuity (LogMAR), it showed a declined trend from baseline (0.5 ± 0.3) to M6 (0.4 ± 0.2), but without statistical significance (P = 0.096). Subgroup analyses revealed that TNFi history related to decreased golimumab efficacy. In addition, 13.3% of patients had adverse events, including elevated liver enzymes (6.7%), fatigue (3.3%), and rash (3.3%). CONCLUSION: Golimumab is effective and safe for refractory NIU treatment, while a large-scale trial is still needed for verification.

Effects of Different Drug Therapies and COVID-19 mRNA Vaccination on Semen Quality in a Man with Ankylosing Spondylitis: A Case Report.

Background and Objectives: Ankylosing spondylitis (AS) is a condition that affects 0.1% to 0.5% of the adult population. The aim of this case report was to investigate the possible effects of the drugs taken for treatment of AS as well as mRNA vaccination for COVID-19 on semen quality by performing a highly detailed analysis. Materials and Methods: Sperm characteristics were examined by light microscopy, DNA fragmentation (DFI) was analysed by flow cytometry and morphology was evaluated by transmission electron microscopy (TEM). Results: Semen analysis under therapy with (1) celecoxib and sulphasalazine showed: concentration 47 million/mL, 53% progressive motility, 7% normal morphology and 9.6% DFI, (2) Golimumab and before mRNA Vaccination showed: concentration 108 million/mL, 82% progressive motility, 1% normal morphology and 7.6% DFI, and (3) Golimumab and after 3 doses of mRNA Vaccination showed: concentration 142 million/mL, 85% progressive motility, 1% normal morphology and 6.8% DFI. TEM revealed head, neck and tail abnormalities, as well as the presence of cells with incomplete spermiogenesis white cells and phagocytes in the sample under therapy with celecoxib and sulphasalazine. Golimumab treatment lead to an increased incidence of elongated heads but in general reduced inflammation as no white cells were evident in TEM. Conclusion: The anti-inflamatory drugs celecoxib and sulphasalazine had no adverse effect on sperm quality as all parameters were within normal limits and the patient achieved under that treatment 2 pregnancies following natural conception that lead to the birth of a healthy boy and girl respectively. Anti-TNFa treatment with Golimumab exerted a negative effect on morphology but not on concentration, motility and DFI. After 3 doses of mRNA Vaccination, sperm concentration increased while motility, morphology and DFI remained similar to the values before vaccination suggesting no negative effect of the mRNA vaccine for COVID-19 on sperm quality.