Therapeutic Utility and Adverse Effects of Biologic Disease-Modifying Anti-Rheumatic Drugs in Inflammatory Arthritis.

Targeting specific pathologic pro-inflammatory cytokines or related molecules leads to excellent therapeutic effects in inflammatory arthritis, including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Most of these agents, known as biologic disease-modifying anti-rheumatic drugs (bDMARDs), are produced in live cell lines and are usually monoclonal antibodies. Several types of monoclonal antibodies target different pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-17A, IL-6, and IL-23/12. Some bDMARDs, such as rituximab and abatacept, target specific cell-surface molecules to control the inflammatory response. The therapeutic effects of these bDMARDs differ in different forms of inflammatory arthritis and are associated with different adverse events. In this article, we summarize the therapeutic utility and adverse effects of bDMARDs and suggest future research directions for developing bDMARDs.

A Capillary Electrophoresis-Based Method for the Measurement of Hydroxychloroquine and Its Active Metabolite Desethyl Hydroxychloroquine in Whole Blood in Patients with Rheumatoid Arthritis.

A capillary electrophoresis method was developed to detect and measure hydroxychloroquine (HCQ) and its active metabolite desethyl hydroxychloroquine (DHCQ) in whole blood in patients with rheumatoid arthritis. The best separation in terms of peak area reproducibility, migration time, peak shape, and resolution of adjacent peaks was obtained in a 60 cm, 75 µm i.d. uncoated fused-silica capillary using a background electrolyte mixture of an aqueous 55 mmol/L TRIS solution brought to pH 2.6 with phosphoric acid and methanol (85:15) and a voltage and a temperature of separation of 20 kV and 30 °C, respectively. Analytes were separated in less than 12 min, with excellent linearity (R2 ≥ 0.999) in the concentration range of 0.5-8 µmol/L. The recovery of analytes spiked in whole blood was 99-101% for HCQ and 98-99% for DHCQ. Analysis of five samples from patients with rheumatoid arthritis receiving HCQ 400 mg daily yielded mean steady-state concentrations of 2.27 ± 1.61 and 1.54 ± 0.55 µmol/L for HCQ and DHCQ, respectively, with a HCQ to DHCQ ratio of 1.40 ± 0.77.

Behçet's disease uveitis: is there a need for new emerging drugs?

Introduction: Behçet's disease uveitis (BDU) is a potentially blinding disorder. Systemic treatment with disease-modifying anti-rheumatic drugs (DMARDs) is mandatory in patients with intraocular inflammation involving the posterior segment of the eye. Areas covered: This article discusses existing systemic treatment with corticosteroids and conventional and biologic DMARDs as well as adjunctive local therapy in BDU. An overview is provided for a wide range of biologic DMARDs that have shown promise or investigated in clinical trials. Most recently introduced biologic DMARDs and targeted synthetic DMARDs are also reviewed for their potential in the treatment of BDU. Expert opinion: The prognosis of patients with BDU has remarkably improved after the introduction of biologic DMARDs. An expanding therapeutic armamentarium will allow treatment of most refractory cases. The ultimate goal is to provide drug-free remission with preservation of 20/20 vision.

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers.

Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer's disease or myasthenia gravis will be discussed.

Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study.

BACKGROUND: Many patients with rheumatoid arthritis (RA) achieve disease remission with modern treatment strategies. However, having achieved this state, there are no tests that predict when withdrawal of therapy will result in drug-free remission rather than flare. We aimed to identify predictors of drug-free remission in RA. METHODS: The Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study was a unique, prospective, interventional cohort study of complete and abrupt cessation of conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA of at least 12 months duration and in clinical and ultrasound remission discontinued DMARDs and were monitored for six months. The primary outcome was time-to-flare, defined as disease activity score in 28 joints with C-reactive protein (DAS28-CRP) ≥ 2.4. Baseline clinical and ultrasound measures, circulating inflammatory biomarkers, and peripheral CD4+ T cell gene expression were assessed for their ability to predict time-to-flare and flare/remission status by Cox regression and receiver-operating characteristic (ROC) analysis respectively. RESULTS: 23/44 (52%) eligible patients experienced an arthritis flare after a median (IQR) of 48 (31.5-86.5) days following DMARD cessation. A composite score incorporating five baseline variables (three transcripts [FAM102B, ENSG00000228010, ENSG00000227070], one cytokine [interleukin-27], one clinical [Boolean remission]) differentiated future flare from drug-free remission with an area under the ROC curve of 0.96 (95% CI 0.91-1.00), sensitivity 0.91 (0.78-1.00) and specificity 0.95 (0.84-1.00). CONCLUSION: We provide proof-of-concept evidence for predictors of drug-free remission in RA. If validated, these biomarkers could help to personalize immunosuppressant withdrawal: a therapy paradigm shift with ensuing patient and economic benefits.

Changing biological disease modifying treatment for paediatric uveitis in the real world.

IMPORTANCE: Paediatric uveitis is a severe sight-threatening uveitis due to disease progression and treatment failure. Biological agents are a promising new treatment. This study provides real-world data on their use from Sydney, Australia. BACKGROUND: Traditionally corticosteroids and non-biological immunosuppressive agents were used to treat paediatric uveitis, often with poor outcomes. DESIGN: Retrospective, chart review over an 8-year period at a tertiary referral eye hospital. PARTICIPANTS: A total of 27 paediatric uveitis patients treated with biological agents. METHODS: Chart review of demographic data and treatment outcomes. MAIN OUTCOME MEASURES: Treatment efficacy (corticosteroid-sparing effect, topical steroid cessation/reduction, reduction in systemic-steroid sparing agents, change in intraocular inflammation, visual acuity and central macular thickness); treatment failure; and adverse events. Data were collected at biological initiation, 6 weeks, 6 months and 12 months. RESULTS: Biological therapy over 1 year was effective with prednisolone dose reduced to <5 mg/day in five of six patients (83%), number of systemic steroid-sparing agents was reduced to ≤1 in two of four patients (50%) and cessation of topical steroid achieved in 12/41 of eyes (29%). Improvement of anterior chamber cells by two grades occurred in 20/25 eyes (80%), improvement of logMAR to ≤0.3 occurred in 12/18 eyes (67%) and macular oedema decreased in 4/5 eyes (80%). Treatment failure occurred in six eyes (13.01%) and five patients (18.5%) developed an adverse reaction. CONCLUSIONS AND RELEVANCE: Biological therapy was effective in paediatric patients with uveitis. Intraocular inflammation improved with maintained visual acuity, systemic corticosteroid dose decreased and there was a low frequency of adverse events.

Discontinuation of long-term adalimumab treatment in patients with juvenile idiopathic arthritis-associated uveitis.

PURPOSE: The purpose of this study was to evaluate the discontinuation of adalimumab (ADA) treatment in patients with juvenile idiopathic arthritis-associated uveitis (JIAU). METHODS: Patients in whom ADA treatment was initiated for JIAU were included in this retrospective analysis. Reasons for discontinuing ADA treatment in patients with primary treatment response were analysed. RESULTS: Within a group of 387 JIAU patients, 59 of 68 patients who were treated with ADA achieved a sufficient response to treatment within 6 months. Here, 39 patients (66.1 %) were still on therapy at their last follow-up visit (mean treatment duration of 38.3 months, range 12-91). In another 20 patients, ADA had been discontinued after 1 or 2 years or later, in 10 % (n = 2), 45 % (n = 9) and 45 % (n = 9) of patients, respectively (mean 30.6 months; range 10-65). Reasons for discontinuing ADA were reactivation of uveitis (n = 8, 3.93 per 100 patient-years) or arthritis (n = 4; 1.97 per 100 patient-years), or ≥2 years of complete disease inactivity (n = 3, 1.47 per 100 patient-years), adverse events (n = 4; 1.89 per 100 patient-years), or other (n = 1; 0.47 per 100 patient-years). CONCLUSIONS: The data show a good primary response to ADA in patients with refractory JIAU. Due to the increasing rate of adalimumab failure or adverse events during long-term treatment, further treatment options may be required.

Occurrence of adverse events in patients with JIA receiving biologic agents: long-term follow-up in a real-life setting.

OBJECTIVE: The aim of this study was to carry out a safety evaluation of biologic agents in patients with JIA and associated uveitis. METHODS: In three tertiary centres in Finland, all adverse events (AEs) in 348 consecutive patients were collected. AEs were classified according to the Common Terminology Criteria for AEs. RESULTS: A total of 1516 patient-years (py) were included: 710 on etanercept, 591 on infliximab, 188 on adalimumab, 8 on rituximab, 5 on anakinra, 6 on tocilizumab, 6 on abatacept and 1 on golimumab. The median follow-up of an individual patient was 51 months (range 1-155). The most common of the 2902 AEs (191/100 py) observed were mild infections, infusion or injection site reactions and alanine aminotransferase elevations. At least one AE occurred in 319 (92%) patients and 121 (35%) had at least one serious AE (SAE). The rate of SAEs was 11.4/100 py on etanercept, 11.8 on infliximab, 10.1 on adalimumab, 15.7 on abatacept, 31.2 on tocilizumab and 87.5 on rituximab, higher than with most anti-TNF agents (P = 0.005). No cases of malignant neoplasms or tuberculosis were detected. New-onset uveitis occurred in 9 patients, psoriasis or psoriasiform lesions in 13 and IBD in 6. CONCLUSION: Mild and moderate AEs in patients with JIA treated with biologics were more frequent than previously reported. SAEs were observed in one-third of the patients, but SAEs seldom led to drug discontinuation.

Psoriatic arthritis: current therapy and future approaches.

PsA is a systemic inflammatory condition that affects 20-30% of patients with psoriasis. It is characterized by potential involvement of diverse tissues, including peripheral and axial joints, enthesitis, dactylitis and skin and nail disease. The degree of involvement in each domain can vary over time in individual patients and can differ substantially between PsA patients. The clinical heterogeneity along with the varying extent of severity and activity can pose significant challenges to treatment. Although some studies had suggested immunopathophysiological similarities between PsA and RA, more recently important distinctions have been defined. Similarly, although some immunomodulatory therapies have proved effective for both PsA and RA, recent data suggest distinct responses to certain targeted therapies. Herein, current DMARDs and biologic agents as well as the potential role of emerging therapeutics will be reviewed.

Plasma n-3 fatty acids and clinical outcomes in recent-onset rheumatoid arthritis.

A randomised controlled trial (RCT) of high-dose v. low-dose fish oil in recent-onset rheumatoid arthritis (RA) demonstrated that the group allocated to high-dose fish oil had increased remission and decreased failure of disease-modifying anti-rheumatic drug (DMARD) therapy. This study examines the relationships between plasma phospholipid levels of the n-3 fatty acids in fish oil, EPA and DHA, and remission and DMARD use in recent-onset RA. EPA and DHA were measured in blood samples from both groups of the RCT. The data were analysed as a single cohort, and Cox proportional hazards models were used to examine relationships between plasma phospholipid (PL) EPA and DHA and various outcome measures. When analysed as a single cohort, plasma PL EPA was related to time to remission, with a one unit increase in EPA (1% total fatty acids) associated with a 12% increase in the probability of remission at any time during the study period (hazard ratio (HR)=1.12; 95% CI 1.02, 1.23; P=0.02). Adjustment for smoking, anti-cyclic citrullinated peptide antibodies and 'shared epitope' HLA-DR allele status did not change the HR. Plasma PL EPA, adjusted for the same variables, was negatively related to time to DMARD failure (HR=0.85; 95% CI 0.72, 0.99; P=0.047). The HR for DHA and time to remission or DMARD failure were similar in magnitude to those for EPA, but not statistically significant. Biomarkers of n-3 status, such as plasma PL EPA, have the potential to predict clinical outcomes relevant to standard drug treatment of RA patients.

Biological treatment in elderly and young patients with ankylosing spondylitis: TURKBIO real-life data results.

Objectives: This study aims to investigate the effect of age on disease activity and biological treatment in patients with ankylosing spondylitis (AS). Patients and methods: A total of 811 AS patients registered in the TURKBIO registry database between 2011 and 2019 were categorized according to their age at the time of entry into the registry and assigned to one of two groups: young patients, defined as <60 years of age (n=610), and those aged ≥60 years (n=201) were recorded as elderly patients. Demographic, clinical, and laboratory characteristics, along with disease activity markers and other follow-up parameters, as well as current and prior treatments, were electronically recorded during each visit using open-source software. Results: The mean age of the elderly patients was 67±5.8 years, while the mean age of the younger patients was 49.2±10.9 years. Male predominance was lower in the older AS group compared to the younger AS group (p=0.002). During follow-up period, 397 patients (comprising 318 young and 79 elderly individuals) had a history of using at least one biological disease-modifying agent (bDMARD). There was no significant difference between the groups in terms of DMARD and bDMARD-use distributions. First tumor necrosis factor inhibitor (TNFi) retention rates were found to be similar in both groups over 10 years of follow-up. Adverse events were found to be similar in young (19.9%) and elderly (26.8%) AS patients. Conclusion: Research in the TURKBIO cohort reveals that both older and younger patients with AS exhibited similar disease activity levels with comparable treatment approaches. Moreover, the results of TNFi treatments in elderly patients were the same as those observed in younger patients, with no notable increase in safety concerns.

Cost-effectiveness analysis of upadacitinib as a treatment option for patients with rheumatoid arthritis in the Kingdom of Saudi Arabia.

AIM: To evaluate cost-effectiveness of upadacitinib (targeted synthetic-disease modifying anti-rheumatic drug [ts-DMARD]) as first-line (1 L) treatment versus current treatment among patients with rheumatoid arthritis (RA) in the Kingdom of Saudi Arabia (KSA), who had an inadequate response to prior conventional-synthetic (csDMARDs) and/or biologic-DMARDs (bDMARDs). METHODS: This Excel-based model included patients with moderate (Disease Activity Score [DAS28]: >3.2 to ≤5.1) or severe RA (DAS28 > 5.1). Cost-effectiveness of current treatment (1 L: adalimumab-originator/biosimilar; second-line (2 L): other bDMARDs/tofacitinib) was compared against a new treatment involving two scenarios (1 L: upadacitinib, 2 L: adalimumab-biosimilar [scenario-1]/adalimumab-originator [scenario-2]) for a 10-year time-horizon from societal perspective. Model outcomes included direct and indirect costs, quality-adjusted life-years (QALYs), hospitalization days, number of orthopedic surgeries, and incremental cost-utility ratio (ICUR) per QALY. RESULTS: With the current pathway, estimated total societal costs for 100 RA patients over 10-year period were Saudi Riyal (SAR) 50,450,354 (United States dollars [USD] 13,453,428) (moderate RA) and SAR50,013,945 (USD13,337,052) (severe RA). New pathway (scenario-1) showed that in patients with moderate-to-severe RA, upadacitinib led to higher QALY gain (+8.99 and +15.63) at lower societal cost (cost difference: -SAR2,023,522 [-USD539,606] and -SAR3,373,029 [-USD899,474], respectively). Thus, as 1 L, upadacitinib projects "dominant" ICUR per QALY over current pathway. Moreover, in alternate pathway (scenario-2), upadacitinib also projects "dominant" ICUR per QALY for patient with severe RA (QALY gain: +15.63; cost difference: -SAR 164,536 [-USD43,876]). However, moderate RA was associated with additional cost of SAR1,255,696 (USD334,852) for improved QALY (+8.99) over current pathway (ICUR per QALY: SAR139,742 [USD37,264]). Both scenarios resulted in reduced hospitalization days (scenario-1: -14.83 days; scenario-2: -11.41 days) and number of orthopedic surgeries (scenario-1: -8.36; scenario-2: -6.54) for moderate-to-severe RA over the current treatment pathway. CONCLUSION: Upadacitinib as 1 L treatment in moderate-to-severe RA can considerably reduce healthcare resource burden in KSA, majorly due to reduced drug administration/monitoring/hospitalization/surgical and indirect costs.

CD45RA-Foxp3(high) activated/effector regulatory T cells in the CCR7 + CD45RA-CD27 + CD28+central memory subset are decreased in peripheral blood from patients with rheumatoid arthritis.

Human CD4+ T cells can be classified as either naïve, central memory (TCM), or effector memory (TEM) cells. To identify the CD4+ T cell subsets most important in the pathogenesis of rheumatoid arthritis (RA), we phenotypically defined human CD4+ T cells as functionally distinct subsets, and analyzed the distribution and characteristics of each subset in the peripheral blood. We classified CD4+ T cells into six novel subsets based on the expression of CD45RA, CCR7, CD27, and CD28. The CCR7 + CD45RA-CD27 + CD28+ TCM subset comprised a significantly smaller proportion of CD4+ T cells in RA patients compared to healthy controls. The frequency of TNF-α-producing cells in the CCR7-CD45RA-CD27 + CD28+ TEM subset was significantly increased in RA. Furthermore, within the CCR7 + CD45RA-CD27 + CD28+ TCM subset, which was decreased in periperal blood from RA, the proportions of total Foxp3+ Treg cells and CD45RA-Foxp3(high) activated/effector Treg cells were significantly lower in RA patients. Our findings suggest that the increased proportion of TNF-α-producing cells and the decreased proportion of CD45RA-Foxp3(high) activated/effector Treg cells in particular subsets may have critical roles in the pathogenesis of RA.

Systemic amyloidosis with amyloid goiter: An autopsy report.

Systemic amyloidosis is a rare but potentially lethal disease characterized by amyloid accumulation in all organs. Amyloid goiter is an extremely rare pathological lesion characterized by thyroid gland enlargement with fat deposition due to local or systemic amyloidosis. A 60 s woman with rheumatoid arthritis was found unconscious on her bed and declared dead after failed cardiopulmonary resuscitation. Postmortem computed tomography showed severe enlargement of the heart and thyroid glands, suggestive of cardiac hypertrophy and thyroidism. Histological examination revealed amorphous eosinophilic deposits with parenchymal cell destruction in all organs, including the heart and thyroid gland. Abnormal amorphous deposits in the tissues were positive for amyloid A as noted upon Congo red immunohistochemical staining and birefringence microscopy, confirming systemic amyloidosis with amyloid goiter. Serum biochemical analysis revealed increased levels of C-reactive protein; anti-cyclic citrullinated peptide antibody; creatinine kinase-myoglobin binding and N-terminal pro-brain natriuretic peptide; and thyroglobulin, free triiodothyronine, and free thyroxine, indicating systemic inflammation, active rheumatoid arthritis, heart failure, and destructive hyperthyroidism, respectively. These findings suggested that the cause of death was undiagnosed heart failure due to secondary systemic amyloid A (AA) amyloidosis related to rheumatoid arthritis. In addition, destructive hyperthyroidism caused by systemic AA amyloidosis may have also been one of the causes of death as indicated by cardiac overload. To the best of our knowledge, this is the first forensic autopsy report of cardiac amyloidosis with amyloid goiter. In conclusion, this autopsy report highlights the importance of increased awareness and early intervention for severe but treatable complications of systemic amyloidosis.

Efficacy and Safety of Upadacitinib in Patients with Psoriatic Arthritis: 2-Year Results from the Phase 3 SELECT-PsA 1 Study.

INTRODUCTION: Efficacy and safety of the Janus kinase (JAK) inhibitor upadacitinib (UPA) was evaluated in patients with psoriatic arthritis (PsA) through week 104 of the ongoing long-term extension of the phase 3 trial SELECT-PsA 1. METHODS: Exploratory analyses of all primary and secondary endpoints (non-responder imputation and as observed for binary endpoints; mixed-effect model repeated measures and as observed for continuous endpoints), and summary of treatment-emergent adverse events, in patients receiving UPA 15 mg (UPA15) or 30 mg (UPA30) once daily, or adalimumab 40 mg (ADA) every other week, through week 104 are reported. RESULTS: Of 1704 patients, 25.4% discontinued the study drug by week 104. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), ≥ 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), or minimal disease activity (MDA) were maintained through week 104; greater responses by nominal P value were observed with UPA15 and UPA30 versus ADA for ACR20/50/70 and MDA. Mean change from baseline in modified total Sharp/van der Heijde Score (mTSS) was similar across groups and to week 56 results. The safety profile of UPA was generally comparable to ADA and not altered from week 56 data. Rates of serious infection, herpes zoster, anemia, neutropenia, lymphopenia, and elevated creatine phosphokinase remained numerically higher with UPA15 and/or UPA30 versus ADA. Rates of malignancies excluding non-melanoma skin cancer (NMSC), major adverse cardiovascular events, and venous thromboembolism were similar across groups; rates of NMSC were higher with UPA versus ADA. Two deaths were reported with UPA15, one with UPA30, and one with ADA. CONCLUSIONS: In PsA patients, efficacy responses were similar or greater with UPA15 or UPA30 versus ADA through week 104, and inhibition of radiographic progression was maintained. No new safety risks were identified with exposure to UPA through 2 years (week 104). CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03104400.

Efficacy of JAK Inhibitors versus DMARDs in the Treatment of Polymyalgia Rheumatica in China.

Objective: This retrospective analysis was to assess the role of Janus kinases (JAK) inhibitors compared with conventional disease modifying anti-rheumatic drugs (DMRADs) in the treatment of polymyalgia rheumatica (PMR) with glucocorticoids (GCs) reduction. Methods: Clinical information was collected from PMR patients in the JAK inhibitor group and the DMARDs group from January 2020 to August 2021 at Jiaxing first Hospital. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), albumin and dose of GCs before and after treatment were compared between two groups. Results: Thirty female patients with PMR were included into this study. The dose of GCs in the JAK inhibitor group was significantly lower than in the DMARDs group at baseline and at 3 and 6 months after treatment. There were no significant differences in various laboratory parameters (including CRP, ESR, Hb and albumin) between two groups (P > 0.05) except that Hb in the DMARDs group was significantly higher than in the JAK inhibitor group at 3 and 6 months after treatment (P<0.05). One patient in the JAK inhibitor group developed herpes zoster, and received tofacitinib treatment after herpes zoster was relieved. Conclusion: Our study indicates that JAK inhibitors in the treatment of PMR are as effective as DMRADs and are also helpful for the reduction of GCs dose.

Comparative risk of herpes zoster in patients with psoriatic disease on systemic treatments: a systematic review and network meta-analysis.

Background: Numerous previous studies have examined risk of herpes zoster (HZ) in psoriatic disease; however, the results of these studies are conflicting and the relative risks associated with different treatments remain largely unknown. In this meta-analysis, we examined the relative risk of HZ associated with systemic treatments for psoriatic disease. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched to identify relevant English-language studies published up to April 2021. Data were extracted using a standardized data extraction form. Network meta-analyses (NMA) was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We examined the differences in HZ risk (incidence rate ratio; IRR) between treatments using a random-effects model for direct pairwise comparisons and NMA. The surface under the cumulative ranking area was calculated to rank the HZ risk for each treatment condition. Results: This study analyzed 13 studies including 19 treatment arms involving a total of 443,104 patients with psoriatic disease. Corticosteroids (CS) [IRR, 2.56; 95% confidence interval (CI), 1.59-4.13], a Janus kinase inhibitor (JAKi; tofacitinib) (IRR, 2.34; 95% CI, 1.03-5.32), infliximab (IRR, 2.32; 95% CI, 1.27-4.21), conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) + CS (IRR, 2.26; 95% CI, 1.23-4.17), anti-tumor necrosis factor-α (anti-TNF-α) + csDMARDs and/or CS (IRR, 2.13; 95% CI, 1.38-3.31), csDMARDs (IRR, 1.62; 95% CI, 1.18-2.22), and anti-TNF-α except infliximab (IRR, 1.61; 95% CI, 1.13-2.30) were all associated with a significantly higher HZ risk compared to controls. CS treatment possessed the highest HZ risk, followed by infliximab and JAKi (tofacitinib). Phosphodiesterase-4 inhibitor, anti-interleukin-17, -23 or -12/23, phototherapy, and acitretin showed a risk similar to controls without significant differences. Conclusion: The NMA demonstrated CS, infliximab, and JAKi (tofacitinib), and several combination treatments were associated with higher HZ risk in patients with psoriasis and psoriatic arthritis. Differences in HZ risk should be taken into consideration when considering optimal psoriasis treatment.

Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study.

BACKGROUND: To evaluate the efficacy and safety of HLX01, a rituximab biosimilar, as combination therapy with methotrexate in Chinese patients with active rheumatoid arthritis who had inadequate responses to methotrexate. METHODS: In this double-blind, placebo-controlled phase 3 trial, biologic-naïve patients with moderate-to-severe active rheumatoid arthritis and inadequate responses to methotrexate were randomized 2:1 to receive 1000 mg HLX01 or placebo intravenously on days 1 and 15. On the first day of weeks 24 and 26, patients in both groups received 1000 mg HLX01 via intravenous infusion. The primary endpoint was the American College of Rheumatology (ACR) 20 response rate at week 24. Secondary endpoints including efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics were assessed up to week 48. RESULTS: Between 28 May 2018 and 11 September 2020, 275 patients were randomized to the HLX01 group (n = 183) or the placebo group (n = 92). At week 24, the proportion of patients achieving ACR20 response was significantly greater in the HLX01 group compared with the placebo group in the intention-to-treat population (60.7% vs 35.9%; P < 0.001) and per-protocol set (60.3% vs 37.1%; P < 0.001). Most secondary efficacy endpoints favoured HLX01 when assessed at weeks 12, 24, 36 and 48. Incidences of treatment-emergent adverse events were similar between groups. Infusion-related reactions occurred more frequently following the initial two doses of HLX01 than the subsequent doses. CONCLUSIONS: HLX01 plus methotrexate improved clinical outcomes compared with placebo in Chinese patients with rheumatoid arthritis who had inadequate responses to methotrexate. This treatment regimen was well tolerated, showing comparable safety profiles to placebo. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03522415 . Registered on 11 May 2018.

Biological and Methotrexate Survival after Pregnancy in Patients With a Rheumatic Disease.

Objective: Patients with a rheumatic disease who discontinue their disease-modifying anti-rheumatic drug (DMARD) due to pregnancy often wonder if treatment will be as effective after pregnancy. This study investigates the effect of a temporary discontinuation of DMARDs due to pregnancy on the effectiveness of the same DMARD postpartum in patients with a rheumatic disease. Methods: Pregnant, rheumatic patients were derived from the Preconceptional Counseling in Active Rheumatoid Arthritis (PreCARA) cohort. DMARD-survival after pregnancy, for biological and methotrexate (MTX) therapy, was analyzed and compared to controls with stable DMARD-treatment from a retrospective cohort. Results: In total, 234 patients were included, of whom 114 patients had stable biological or MTX treatment before their pregnancy. After pregnancy, 40 out of 56 (71%) patients restarted their biological, for MTX this was 49%. One year after restart, and censoring for a following pregnancy, 88.9% of patients were still using their biological, and 85% still used their MTX (p = 0.92). Compared to the matched controls the survival after pregnancy was significantly lower 1 year after restart for both biologicals (98.3%) and MTX (99.6%); p = 0.002 and p < 0.001 respectively; 3 years after restart this significant difference was no longer observed (p = 0.50 and p = 0.33, respectively). Conclusion: Effective DMARD (biological or MTX) treatment before pregnancy that was discontinued due to pregnancy seems effective after pregnancy. Although DMARD-survival was higher in the control group 1 year after restart, the percentage of patients with effective treatment was still very good (>85%). In addition, this difference was no longer observed after 3 years.