Exploring the effect on primary endpoints in trials testing targeted therapy interventions for rheumatoid arthritis: a meta-epidemiological study on the appropriate use of a core outcome set.

OBJECTIVES: To explore which core domain is best associated with the American College of Rheumatology (ACR) 20% response in trials assessing the effect of targeted interventions in rheumatoid arthritis (RA). METHODS: A meta-epidemiological study was performed on randomised trials investigating biologics and targeted agents compared with placebo or conventional disease-modifying antirheumatic drugs in patients with RA. The main outcome measures were ORs for the ACR 20% response and at least one of the eight core domains according to the existing RA core outcome set (COS) analysed based on standardised mean differences. RESULTS: 115 trials involving 55 422 patients with RA were eligible. The OR for achieving ACR 20% response was 3.19 (95% CI 2.96 to 3.44) for the experimental interventions relative to the comparators. The median number of COS domains reported was 6; 18 trials reported only 1 domain, 17 all 8. Univariable meta-regression analyses indicated that each of the eight core domains was significantly associated with ACR 20% response, yet improvements in physical disability explain a successful ACR 20% response the most. Including only trials reporting on all eight core domains, univariable meta-regression analyses proved improvement in fatigue to explain a successful ACR 20% response the most. CONCLUSIONS: Within this dataset, it is evident that the conclusions concerning our primary objective were significantly influenced by both the amount and characteristics of missing data. Our data suggest that fatigue could be more important for the primary endpoint than previously assumed, but this is based on limited data.

Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX.

OBJECTIVES: Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease associated with somatic ubiquitin-like modifier-activating enzyme 1 (UBA1) mutations. We aimed to evaluate the efficacy and safety of targeted therapies. METHODS: Multicentre retrospective study including patients with genetically proven VEXAS syndrome who had received at least one targeted therapy. Complete response (CR) was defined by a clinical remission, C-reactive protein (CRP) ≤10 mg/L and a ≤10 mg/day of prednisone-equivalent therapy, and partial response (PR) was defined by a clinical remission and a 50% reduction in CRP levels and glucocorticoid dose. RESULTS: 110 patients (median age 71 (68-79) years) who received 194 targeted therapies were included: 78 (40%) received Janus kinase (JAK) inhibitors (JAKi), 51 (26%) interleukin (IL)-6 inhibitors, 33 (17%) IL-1 inhibitors, 20 (10%) tumour necrosis factor (TNFα) blockers and 12 (6%) other targeted therapies. At 3 months, the overall response (CR and PR) rate was 24% with JAKi, 32% with IL-6 inhibitors, 9% with anti-IL-1 and 0% with TNFα blockers or other targeted therapies. At 6 months, the overall response rate was 30% with JAKi and 26% with IL-6 inhibitors. Survival without treatment discontinuation was significantly longer with JAKi than with the other targeted therapies. Among patients who discontinued treatment, causes were primary failure, secondary failure, serious adverse event or death in 43%, 14%, 19% and 19%, respectively, with JAKi and 46%, 11%, 31% and 9%, respectively, with IL-6 inhibitors. CONCLUSIONS: This study shows the benefit of JAKi and IL-6 inhibitors, whereas other therapies have lower efficacy. These results need to be confirmed in prospective trials.

Multi-Disciplinary Expert Perspective on the Management of Type 2 Inflammation-Driven Severe CRSwNP: A Brief Overview of Pathophysiology and Recent Clinical Insights.

Severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disabling airway disease that significantly impacts patients' lives through the severity of symptoms, the need for long-term medical treatment and the high risk of recurrence post-surgery. Biological agents targeting type 2 immune responses underlying the pathogenesis of CRSwNP have shown effectiveness in reducing polyp size and eosinophilic infiltrate, and in decreasing the need for additional sinus surgeries. However, despite recent progress in understanding and treating the disease, type 2 inflammation-driven severe CRSwNP continues to pose challenges to clinical management due to several factors such as persistent inflammation, polyp recurrence, heterogeneity of disease, and comorbidities. This article presents the findings of a scientific discussion involving a panel of ear, nose and throat (ENT) specialists and pulmonologists across Sweden and Finland. The discussion aimed to explore current management practices for type 2 inflammation-driven severe CRSwNP in the Nordic region. The main topics examined encompassed screening and referral, measurements of disease control, treatment goals, and future perspectives. The experts emphasized the importance of a collaborative approach in the management of this challenging patient population. The discussion also revealed a need to broaden treatment options for patients with type 2 inflammation-driven CRSwNP and comorbid conditions with shared type 2 pathophysiology. In light of the supporting evidence, a shift in the disease model from the presence of polyps to that of type 2 inflammation may be warranted. Overall, this discussion provides valuable insights for the scientific community and can potentially guide the future management of CRSwNP.

Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

Efficacy, Safety, and Continuation of Biological Therapy in Older Patients with Asthma in a Real-World Setting: A Retrospective Observational Study.

Background: Major randomized clinical trials have shown that biological therapy can reduce the exacerbation rate and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data on the continuation, efficacy, and safety of biological therapy in older patients with asthma are limited. Therefore, the aim of this study was to evaluate the differences in the continuation rate, efficacy, and safety of biological therapy between older (≥ 65 years) and younger (< 65 years) patients with asthma. Methods: In this single-center retrospective observational study, we collected clinical data of patients with asthma who were administered biological drugs such as omalizumab, mepolizumab, benralizumab, and dupilumab between April 2009 and August 2022. We comparatively analyzed the continuation, efficacy, and safety of biological therapy between older (age ≥ 65 years) and younger patient (age < 65 years) groups. The reasons for discontinuation or switching of biological drugs were also evaluated. Results: Sixty-two (31 older and 31 younger) patients were treated with 91 biologics during the observational period. The mean age of older patients was 74.3 ± 5.1 years and that of younger patients was 48.0 ± 14.0 years. The continuation rate of biological therapy was not significantly different between the groups. Social background was the most common reason for discontinuation of biological therapy in both groups, and insufficient effect was the most common reason for switching to biological drugs. Asthma exacerbations decreased in both groups within the first 12 months of biologic therapy. The dosage of OCS tended to decrease in the older group and significantly decrease in the younger group. Conclusion: Biologic therapy for older patients with asthma can be continued, with efficacy and safety similar to those in younger patients with asthma.

Cancer biotherapy: review and prospect.

Malignant tumors pose a grave threat to the quality of human life. The prevalence of malignant tumors in China is steadily rising. Presently, clinical interventions encompass surgery, radiotherapy, and pharmaceutical therapy in isolation or combination. Nonetheless, these modalities fail to completely eradicate malignant tumor cells, frequently leading to metastasis and recurrence. Conversely, tumor biotherapy has emerged as an encouraging fourth approach in preventing and managing malignant tumors owing to its safety, efficacy, and minimal adverse effects. Currently, a range of tumor biotherapy techniques are employed, including gene therapy, tumor vaccines, monoclonal antibody therapy, cancer stem cell therapy, cytokine therapy, and adoptive cellular immunotherapy. This study aims to comprehensively review the latest developments in biological treatments for malignant tumors.

Vedolizumab Safety During Pregnancy and Lactation in a Patient with Ulcerative Colitis: A Case Report.

Background: Inflammatory bowel disease (IBD) affects young adults of reproductive age, and questions related to pregnancy and breastfeeding are common in clinical practice. Most medications used to treat IBD are considered safe during pregnancy, except methotrexate and small molecules such as tofacitinib. Despite few studies regarding vedolizumab (VDZ) safety, it appears to be safe during pregnancy. Therefore, this study aimed to report the management of ulcerative colitis in pregnant patient refractory to anti-tumor necrosis factor (TNF) agents using VDZ. Case Report: A female, 38 years old, with ulcerative colitis was refractory to conventional treatment with mesalazine, sulfasalazine, and azathioprine. She was hospitalized at six weeks of gestation with severe acute colitis requiring the use of infliximab (IFX) to induce remission. She had a spontaneous abortion at nine weeks of gestation after the second dose of IFX. Since there was no endoscopic improvement after six months of IFX treatment, VDZ treatment was initiated. During the VDZ infusion period, the patient discovered that she was pregnant with twins, leading to the discussion of the risks and benefits of continuing the VDZ. The patient presented with disease clinical remission with the use of VDZ, and the babies were born at 34 weeks of gestation without complications. Breastfeeding was also performed without complications. Conclusion: Continued VDZ medication is safe during pregnancy and breastfeeding, with adverse events similar to anti-TNF therapy.

[The effectiveness of targeted therapy of various genetically engineered biological drugs in the treatment of bronchial asthma].

This article presents the experience of successfully switching therapy from omalizumab 150 mg to benralizumab 30 mg/1 ml in a patient with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs. The effectiveness of biological therapy was evaluated when switching from omalizumab 150 mg subcutaneously at a dose of 600 mg for 36 weeks. Therapy for the drug benralizumab 30 mg/1 ml subcutaneously the first three injections monthly, the rest a month later for 52 weeks with bronchial asthma (BA), a severe uncontrolled course with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs in a patient Ch., born in 2004. Switching therapy from omalizumab 150 mg to benralizumab 30 mg/1 ml allowed to achieve complete control of asthma symptoms (AST = 23 points), to achieve the absence of asthma exacerbations during 52 weeks, restore respiratory function to normal values, as well as improve the quality of life. The study reflects the good tolerability, high efficacy and safety of biological therapy when switching from one genetically engineered biological drug (GIBP) omalizumab 150 mg to another GIBP benralizumab 30 mg/1 ml in severe uncontrolled asthma with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs. Therapy with benralizumab 30 mg/1 ml in severe BA has demonstrated a more effective clinically significant improvement in the course of the disease, control of symptoms of the disease. Reduction of exacerbations, normalization of respiratory function indicators, complete control of the disease has been achieved. Consequently, the use of different biological molecules for the therapy of BA with a combined allergic and eosinophilic phenotype contributes to achieving disease control, improving the patient's quality of life and reducing the dose of oral glucocorticosteroids. The targeted biological drug benralizumab 30 mg/1 ml has a targeted effect on the key links in the pathogenesis of severe uncontrolled asthma with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs and reduces the burden of severe disease.

The failure of biological treatment in axial spondyloarthritis is linked to the factors related to increased intestinal permeability and dysbiosis: prospective observational cohort study.

BACKGROUND: A significant number of patients with axial spondyloarthritis (axSpA) do not respond to biological therapy. Therefore, we decided to investigate the specificity of this group of patients and, in particular, whether haptoglobin (Hp), its polymorphism and zonulin, in addition to other clinical features, are predictors of poor response to biological treatment. METHODS: 48 patients with axSpA who were unsuccessfully treated with standard drugs were converted to biological treatment, and from this time on, a 12-week follow-up was started to assess the failure of biological treatment (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decrease < 2 points). Predictors of treatment failure were identified using logistic regression analysis. RESULTS: 21% of subjects had biological treatment failure. Patients who had a higher zonulin level, a history of frequent infections, were older, had inflammatory bowel disease (IBD), had a lower Hp level at the time of inclusion in biological therapy showed an increased risk of treatment failure. CONCLUSIONS: The results of the study support the hypothesis that the effectiveness of biological treatment of axSpA is limited by changed microbiota and intestinal epithelial barrier dysfunction, as an increased risk of biological treatment failure was observed in patients who were older, had higher zonulin level, IBD and repeated courses of antibiotics due to frequent infections. Therefore, starting biological treatment should be followed by reducing intestinal permeability and regulating the disturbed gut microbiome.

Childhood-Onset Non-Infectious Uveitis in the "Biologic Era". Results From Spanish Multicenter Multidisciplinary Real-World Clinical Settings.

OBJECTIVE: To characterize and describe clinical experience with childhood-onset non-infectious uveitis. STUDY DESIGN: A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared. RESULTS: IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae [28%], cataracts [16%], band keratopathy [14%], ocular hypertension [11%] and cystoid macular edema [10%]) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (p < 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae [31%] and cataracts [9.6%]) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use. CONCLUSION: Prognosis of childhood uveitis has improved in the "biologic era," particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.

[Effectiveness and safety of biological therapy in patients with severe asthma in a real clinical practice].

AIM: To assess effectiveness and safety of biological therapy in patients with severe asthma during 5 yr follow-up. MATERIALS AND METHODS: We recruited 129 adult outpatients (29% males) aged 18-81 yrs with severe asthma were followed up during 5 yrs and were examined for every 3-6 months. Eighty five patients were treated by conventional therapy (ICS/LABA ± tiotropium, montelukast, OCS) only and 44 pts additionally received biologicals (оmalizumab - 9 pts, мepolizumab - 8 pts, benralizumab - 11 pts, dupilumab - 16 pts). Pulmonary function tests were measured by dry spirometer (2120, Vitalograph Ltd., UK). Eosinophil count in blood was assessed by automatic haemoanalyser. Fraction of exhaled nitric oxide was measured by a chemiluminescence analyzer (LR4100; Logan Research, UK). Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and SGRQ. RESULTS: The use of biologicals led to a more significant reduction of exacerbations and OCS use, improvement of lung function, asthma control and quality of life, decrease of eosinophil and fraction of exhaled nitric oxide than conventional therapy of severe asthma (p<0.05). Systemic side effects were not registered, frequency of local adverse reactions (edema, hyperemia and itching at injection site) was 14%. CONCLUSION: Long-term use of biologicals added to conventional therapy in patients with severe asthma is characterized by high effectiveness and favorable safety profile.

A Rare Case of IgG4-Related Disease Causing Inflammatory Breast Mass Successfully Treated with Anti-CD20 Biological Therapy: A Discussion of Clinical Case with Literature Review.

We report a rare yet successful utilisation of anti-CD20 therapy using rituximab for treatment of a case of IgG4-related mastitis proven by clinical, serological, and histopathological evidence. This was affecting a mid-aged female who was referred to the rheumatology clinic by the breast surgeons to help assessing for the possibility of an underlying inflammatory process involving the breast tissue unilaterally. The clinical course was apparently complex with an onset of an induration in the right lateral superior quadrant of the breast with mild discomfort and heaviness sensation. This increased over a course of 2 weeks before presentation to the general surgery clinic. Subsequent investigations confirmed that the case was IgG4-related mastitis and a trial of steroids and disease modifying anti-rheumatic drugs (DMARDs) was partially helpful, but not to a full degree, mandating the utilisation of a more advanced mode of therapy, so rituximab was selected. LEARNING POINTS: Consider inflammatory conditions including IgG4-related disease in the differential diagnosis of lumps including breast masses.IgG4 disease is a rare condition but can have complex clinical course and significant complications that need a low threshold of suspicion in terms of diagnosis.Occasionally, a repeat study and re-reading of histopathological specimen with appropriate immunostaining can open the way for accurate diagnosis in challenging cases with an unreached diagnosis.

Type I interferon blockade with anifrolumab in patients with systemic lupus erythematosus modulates key immunopathological pathways in a gene expression and proteomic analysis of two phase 3 trials.

INTRODUCTION: Anifrolumab is a type I interferon (IFN) receptor 1 (IFNAR1) blocking antibody approved for treating patients with systemic lupus erythematosus (SLE). Here, we investigated the immunomodulatory mechanisms of anifrolumab using longitudinal transcriptomic and proteomic analyses of the 52-week, randomised, phase 3 TULIP-1 and TULIP-2 trials. METHODS: Patients with moderate to severe SLE were enrolled in TULIP-1 and TULIP-2 and received intravenous anifrolumab or placebo alongside standard therapy. Whole-blood expression of 18 017 genes using genome-wide RNA sequencing (RNA-seq) (pooled TULIP; anifrolumab, n=244; placebo, n=258) and 184 plasma proteins using Olink and Simoa panels (TULIP-1; anifrolumab, n=124; placebo, n=132) were analysed. We compared treatment groups via gene set enrichment analysis using MetaBase pathway analysis, blood transcriptome modules, in silico deconvolution of RNA-seq and longitudinal linear mixed effect models for gene counts and protein levels. RESULTS: Compared with placebo, anifrolumab modulated >2000 genes by week 24, with overlapping results at week 52, and 41 proteins by week 52. IFNAR1 blockade with anifrolumab downregulated multiple type I and II IFN-induced gene modules/pathways and type III IFN-λ protein levels, and impacted apoptosis-associated and neutrophil extracellular traps-(NET)osis-associated transcriptional pathways, innate cell activating chemokines and receptors, proinflammatory cytokines and B-cell activating cytokines. In silico deconvolution of RNA-seq data indicated an increase from baseline of mucosal-associated invariant and γδT cells and a decrease of monocytes following anifrolumab treatment. DISCUSSION: Type I IFN blockade with anifrolumab modulated multiple inflammatory pathways downstream of type I IFN signalling, including apoptotic, innate and adaptive mechanisms that play key roles in SLE immunopathogenesis.

[Take-home messages from the 2nd COPD 2023 Biennial of the French Society of Respiratory Diseases. Placing the patient at the center of the care pathway]. / Principaux messages de la deuxième Biennale BPCO 2023 de la SPLF. Le patient au cœur du parcours de soins.

INTRODUCTION: The second COPD Biennial organized by the COPD working group of the French Society of Respiratory Diseases took place in Paris (Cochin) on 13th December 2023. STATE OF THE ART: Major trends in 2023 were discussed; they encompassed concepts, definitions, biologics, care pathways, pulmonary rehabilitation and complex situations entailed by respiratory infections, cardiovascular comorbidities and pulmonary hypertension, and modalities of oxygen therapy and ventilation. PERSPECTIVES: The different talks underlined major changes in COPD including the concepts of pre-COPD, etiotypes, health trajectories and new definitions of exacerbation. Recent results in biologics for COPD open the door to new pharmacological options. Assessment of current care pathways in France highlighted some causes for concern. For example, pulmonary rehabilitation is a key but insufficiently practiced element. Respiratory infections require careful assessment and treatments. Diagnosis and treatment of cardiovascular comorbidities and pulmonary hypertension are of paramount importance. As of late, oxygen therapy and ventilation modalities have evolved, and are beginning to afford more personalized options. CONCLUSIONS: As regards COPD, a personalized approach is crucial, placing the patient at the center of the care pathway and facilitating coordination between healthcare providers.

Beyond diagnosis: investigating hospital referral impact on biological treatment initiation, hospital admission, and surgery patterns in inflammatory bowel disease - a Danish population based study.

OBJECTIVES: Early biological treatment in patients with inflammatory bowel disease (IBD) is important in disease control. Previous studies have suggested that patients with IBD from Non-Academic Hospitals were less likely to receive biologics. The aims of this study were (1) to use the granular data in the clinical database, GASTROBIO, to study detailed differences in time from IBD diagnosis to first administration of biologics, hospital admission, and surgery in patients referred to Academic Hospitals versus to Non-Academic Hospitals, and (2) to explore differences in disease extent, behavior, and indication for biological treatment. MATERIAL AND METHODS: This was a retrospective cross-sectional descriptive population-based quality study of patients with IBD initiating biologics in the North Denmark Region between 2016 and 2018. Data from GASTROBIO were extracted, namely demographic data, time of diagnosis, biological treatments with indications, hospital admission, and surgery. RESULTS: Of the 146 patients included, 84 were from the Academic and 62 from the Non-Academic Hospitals. No significant differences in median time from diagnosis to (1) treatment, (2) hospital admission or (3) IBD surgery between the groups were observed. A higher percentage of patients with luminal Crohn's disease were treated with biologics at the Academic Hospital (78% and 66%). CONCLUSIONS: Based on the findings of this population-based study, we found no evidence that the referral area had a significant impact on the duration from diagnosis to the initiation of biological treatment, hospital admissions, or surgery. However, the data suggested that fewer patients with luminal Crohn's disease were referred to biologics from Non-Academic Hospitals.

Long-term clinical and radiological effectiveness and safety of ultralow doses of rituximab in rheumatoid arthritis: observational extension of the REDO trial.

BACKGROUND: The REDO trial (REtreatment with Rituximab in RhEmatoid arthritis: Disease Outcome after Dose Optimisation) showed similar disease activity for retreatment with ultralow doses (200 mg and 500 mg per 6 months) compared with standard low-dose rituximab (RTX, 1000 mg per 6 months). We performed an observational extension study of the REDO trial to assess long-term effectiveness. METHODS: Patients from the REDO trial were followed from start of the trial to censoring in April 2021. RTX use was at the discretion of patient and rheumatologist using treat to target. The primary outcome was disease activity (disease activity score in 28 joints C-reactive protein (DAS28-CRP)), analysed using a longitudinal mixed model by original randomisation and time-varying RTX dose. The original DAS28-CRP non-inferiority (NI) margin of 0.6 was used. RTX dose and persistence, safety and radiological outcomes were also assessed. FINDINGS: Data from 126 of 142 REDO patients was collected from 15 December 2016, up to 30 April 2021. Drop-outs continued treatment elsewhere (n=3) or did not consent (n=13).Disease activity did not differ by original randomisation group: 1000 mg mean DAS28-CRP (95% CI) of 2.2 (2.0 to 2.5), 500 mg 2.3 (2.1 to 2.4) and 200 mg 2.4 (2.2 to 2.5). Lower time-varying RTX dose was associated with higher DAS28-CRP (0.22 (95% CI 0.05 to 0.40) higher for 200 mg/6 months compared with 1000 mg/6 months), but remained within the NI-margin. RTX persistence was 93%. Median RTX dose was 978 mg (IQR 684-1413) per year, and no association was found between RTX dose and adverse events or radiological damage. INTERPRETATION: Long-term use of ultralow doses of RTX is effective in patients with rheumatoid arthritis responding to standard dose RTX.

Evolving role of VIADISC for chronic low back and discogenic pain: a narrative review.

INTRODUCTION: Chronic lower back pain is a leading cause of disability and healthcare spending worldwide. Discogenic pain, pain originating from the intervertebral disk, is a common etiology of chronic lower back pain. Currently, accepted treatments for chronic discogenic pain focus only on the management of symptoms, such as pain. There are no approved treatments that stop or reverse degenerating intervertebral discs. Biologic therapies promoting disc regeneration have been developed to expand treatment options. VIADISC™ NP, is a viable disc allograft supplementation that, in a recent trial, demonstrated a significant reduction in pain and increased function in patients suffering from symptomatic degenerative disc disease. AREAS COVERED: This manuscript summarizes the epidemiology and etiology of low back pain, the pathophysiology of degenerative disc disease, current treatments, and a need for newer therapies. The rationale behind intradiscal biologics for the treatment of symptomatic degenerative disc disease is also discussed. EXPERT OPINION: Characterization of the biology leading to disc degeneration has allowed for the development of intradiscal biologics. They may soon be capable of preventing and reversing disc degeneration. Clinical trials have shown promise, but further research into efficacy and safety is needed before these therapies are widely employed.

Impact of DMARD treatment and systemic inflammation on all-cause mortality in patients with rheumatoid arthritis and interstitial lung disease: a cohort study from the German RABBIT register.

OBJECTIVES: To investigate the impact of disease activity and treatment with disease-modifying antirheumatic drugs (DMARDs) on all-cause mortality in patients with rheumatoid arthritis and prevalent interstitial lung disease (RA-ILD). METHODS: Patients with RA-ILD were selected from the biologics register Rheumatoid Arthritis: Observation of Biologic Therapy (RABBIT). Using time-varying Cox regression, the association between clinical measures and mortality was investigated. The impact of DMARDs was analysed by (1) Cox regression considering cumulative exposure (ie, treatment months divided by total months) and (2) time-varying Cox regression as main approach (treatment exposures at monthly level). RESULTS: Out of 15 566 participants, 381 were identified as RA-ILD cases with 1258 person-years of observation and 2.6 years median length of follow-up. Ninety-seven patients (25.5%) died and 34 (35.1%) of these were not receiving DMARD therapy at the time of death. Higher inflammatory biomarkers but not swollen and tender joint count were significantly associated with mortality. Compared with tumour necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs (bDMARDs) exhibited adjusted HRs (aHRs) for mortality below 1, lacking statistical significance. This finding was stable in various sensitivity analyses. Joint aHR for non-TNFi biologics and JAKi versus TNFi was 0.56 (95% CI 0.33 to 0.97). Receiving no DMARD treatment was associated with a twofold higher mortality risk compared with receiving any DMARD treatment, aHR 2.03 (95% CI 1.23 to 3.35). CONCLUSIONS: Inflammatory biomarkers and absence of DMARD treatment were associated with increased risk of mortality in patients with RA-ILD. Non-TNFi bDMARDs may confer enhanced therapeutic benefits in patients with RA-ILD.