The time of equipoise on the use of biological DMARDs in for inflammatory arthritis during pregnancy is finally over: a reappraisal of evidence to optimise pregnancy management.

Active inflammatory arthritis in pregnancy is associated with an increased risk of adverse pregnancy outcomes. Treatment of active inflammation and maintenance of low disease activity with medication reduces these risks. Therapeutic decisions on disease-modifying antirheumatic drugs (DMARDs) in pregnancy are complicated by safety concerns, which have led to inappropriate withdrawal of treatment and consequential harm to mother and fetus.

Poly-Refractory Rheumatoid Arthritis: An Uncommon Subset of Difficult to Treat Disease With Distinct Inflammatory and Noninflammatory Phenotypes.

Objective: To investigate the prevalence of poly-refractory rheumatoid arthritis (RA) defined as failure of all biological (b)/targeted synthetic (ts)-disease-modifying drugs (DMARDs). To further investigate whether patients with persistent inflammatory refractory RA (PIRRA) and noninflammatory refractory RA (NIRRA), determined by objective ultrasound (US) synovitis, have distinct clinical phenotypes in both EULAR difficult-to-treat RA (D2T-RA) and poly-refractory RA groups.

Methods: A cross-sectional study of 1,591 patients with RA on b/tsDMARDs that evaluated D2T-RA criteria and subclassified as poly-refractory if inefficacy/toxicity to at least one drug of all classes.

Breakthrough SARS-CoV-2 infections and prediction of moderate-to-severe outcomes during rituximab therapy in patients with rheumatic and musculoskeletal diseases in the UK: a single-centre cohort study.

Background: Concerns have been raised regarding the reduced immunogenicity of vaccines against COVID-19 in patients with autoimmune diseases treated with rituximab. However, the incidence and severity of breakthrough infections in unbiased samples of patients with specific rheumatic and musculoskeletal diseases are largely unknown. We aimed to assess the incidence of breakthrough SARS-CoV-2 infection, compare rates of moderate-to-severe COVID-19 with any severe infection event, and evaluate predictors of moderate-to-severe COVID-19 outcomes in patients treated with rituximab.

Single-centre experience of refractory rheumatoid arthritis.

Objectives: The aim was to evaluate the proportion of RA patients who are refractory to multiple targeted therapies (TTs) in a real-world cohort of patients in a tertiary rheumatology referral centre, to describe patterns of drug sequencing associated with the development of refractory RA (RefRA) and to identify whether there is a subgroup of RefRA patients in whom successive drugs have shown primary lack of efficacy.

Methods: Patients at a single centre were defined as refractory if they had failed two or more classes of TT and were identified from a dedicated TT clinic database. Reasons for drug failure were recorded, and patients were categorized pragmatically as having mild [failure of two biologic DMARD (bDMARD) classes], moderate [failure of at least three bDMARD classes] or severe [failure of at least two bDMARD classes and JAK inhibitor] refractory disease.

Predicting Sustained Clinical Response to Rituximab in Moderate to Severe Systemic Manifestations of Primary Sjögren Syndrome.

Objective: To assess outcomes of repeat rituximab cycles and identify predictors of sustained clinical response in systemic manifestations of primary Sjögren syndrome (pSS).

Methods: An observational study was conducted in 40 rituximab-treated patients with pSS. Clinical response was defined as a 3-point or more reduction in the European League Against Rheumatism (EULAR) Sjögren Disease Activity Index (ESSDAI) at 6 months from baseline.

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab.

Objectives: Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab.

Methods: We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres.

A Personalized Rituximab Retreatment Approach Based on Clinical and B-Cell Biomarkers in ANCA-Associated Vasculitis.

Background: Time to relapse after rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is variable, and optimal retreatment strategy has remained unclear. In AAV following rituximab induction, the study objective was to evaluate clinical and B-cell predictors of relapse in order to develop a retreatment algorithm.

Methods: A retrospective observational study was conducted in 70 rituximab-treated ANCA-associated vasculitis patients followed up for over 10 years.

Real-world experience of effectiveness of non-medical switch from originator to biosimilar rituximab in rheumatoid arthritis.

Objective: To evaluate the impact of non-medical switch from rituximab originator (RTX-O) to biosimilar (RTX-B) in patients with RA.

Methods: Between October 2017 and October 2019, all patients on RTX-O in our centre requiring re-treatment were switched to RTX-B unless declined by the patient or specified by the treating clinician. Switch strategy effectiveness was assessed retrospectively using DAS28-CRP(3) and RTX retention, with patients remaining on RTX-O as a comparator group.

Biologic Sequencing in Systemic Lupus Erythematosus: After Secondary Non-response to Rituximab, Switching to Humanised Anti-CD20 Agent Is More Effective Than Belimumab.

Rituximab is commonly used for systemic lupus erythematosus (SLE) but secondary non-depletion and non-response (2NDNR) associated with anti-drug antibodies is a notable problem with repeat rituximab cycles. Other B cell-targeted therapies include other anti-CD20 monoclonal antibodies or belimumab. To compare efficacy of switching to alternative anti-CD20 agents vs.

Effect of rituximab or tumour necrosis factor inhibitors on lung infection and survival in rheumatoid arthritis-associated bronchiectasis.

Objective: To evaluate rituximab (RTX) in patients with RA-associated bronchiectasis (RA-BR) and compare 5-year respiratory survival between those treated with RTX and TNF inhibitors (TNFi).

Methods: A retrospective observational cohort study of RA-BR in RTX or TNFi-treated RA patients from two UK centres over 10 years. BR was assessed using number of infective exacerbation/year.

Predicting Severe Infection and Effects of Hypogammaglobulinemia During Therapy With Rituximab in Rheumatic and Musculoskeletal Diseases.

Objective: To evaluate predictors of serious infection events (SIEs) during rituximab (RTX) therapy and effects of hypogammaglobulinemia on SIE rates, and humoral response and its persistence after discontinuation of RTX in the treatment of rheumatic and musculoskeletal diseases (RMDs).

Methods: A retrospective longitudinal study of 700 RMD patients treated with RTX in a single center was conducted. Immunoglobulin levels were measured at baseline and at 4-6 months after each treatment cycle.

Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years' experience at a single centre.

Objective: To evaluate the effect of rituximab (RTX) in patients with RA-related interstitial lung disease (RA-ILD) and identify factors associated with outcome after treatment.

Methods: An observational study of patients with RA-ILD was conducted from a cohort of RTX-treated RA patients in a single centre for >10 years. Progression was defined by any of the following: a decrease of pre-RTX forced vital capacity (FVC) >10% or diffusion capacity of carbon monoxide (DLCO) >15% predicted, worsening of the ILD score or death from progressive ILD.

Repeat cycles of rituximab on clinical relapse in ANCA-associated vasculitis: identifying B cell biomarkers for relapse to guide retreatment decisions.

Objective: To assess clinical and B cell biomarkers to predict relapse after rituximab in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) using retreatment on clinical relapse strategy.

Methods: 35 patients with AAV received treatment with 2×1000 mg rituximab, repeated on clinical relapse (up to 5 cycles). Disease activity was assessed by Birmingham Vasculitis Activity Score (BVAS) and peripheral B cell subsets using highly sensitive flow cytometry (HSFC) as previously described; both performed at baseline and every 3 months.

An extra dose of rituximab improves clinical response in rheumatoid arthritis patients with initial incomplete B cell depletion: a randomised controlled trial.

Objectives: Since clinical non-response to 2×1000 mg rituximab has previously been found to be associated with incomplete B cell depletion, we determined, in a randomised controlled proof of concept study, whether patients with initial incomplete B cell depletion would benefit from an additional infusion of rituximab at week 4.

Methods: Patients with active rheumatoid arthritis despite methotrexate received a first infusion of rituximab 1000 mg and were tested for persistent B cells using highly sensitive flow cytometry on day 15. All received a second infusion of 1 g (according to license), but patients with persistent B cells were subsequently randomised double-blind to receive, 2 weeks later, either a third infusion of 1000 mg rituximab or placebo.

B cell biomarkers of rituximab responses in systemic lupus erythematosus.

Objective: Rituximab appears to be effective in many studies of systemic lupus erythematosus (SLE), with variable initial clinical response and time to relapse. However, results of a randomized controlled trial of rituximab were negative. This study was undertaken to evaluate the effectiveness of rituximab in SLE, using highly sensitive flow cytometry (HSFC), which can define B cell numbers 50-100 times lower than conventional techniques and predicts responses in rheumatoid arthritis.

Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion.

Objective: Studies comparing 500 mg rituximab and 1,000 mg rituximab doses in rheumatoid arthritis have yielded conflicting data on clinical outcomes, but in all of these studies a subgroup of patients has had excellent responses at the lower dose. Historically, it was considered that rituximab uniformly depleted B cells at both doses. Using highly sensitive assays, we have shown that B cell depletion is variable and predictive of clinical response.

Highly sensitive B cell analysis predicts response to rituximab therapy in rheumatoid arthritis.

Objective: In rheumatoid arthritis (RA), B cell depletion occurs in all patients treated with rituximab, but the clinical responses to rituximab are variable. A highly sensitive assay was used to test the hypothesis that B cell depletion is variable, and that incomplete depletion leads to a poorer outcome.

Methods: Sixty patients with active RA unresponsive to anti-tumor necrosis factor agents received two 1-gram infusions of rituximab.

Development of psoriasis after B cell depletion with rituximab.

The B cell-depleting monoclonal antibody rituximab is a novel therapy for the rheumatic diseases, with an increasing body of evidence regarding its safety and efficacy in an expanding range of indications. However, there is uncertainty over its potential use in, and impact on, autoantibody-negative diseases. We describe 3 patients, with no known risk factor for psoriasis, who developed psoriasis (and 1 who also developed features of psoriatic arthritis) after receiving rituximab for a variety of indications, namely, seropositive and seronegative rheumatoid arthritis and systemic lupus erythematosus.

Rituximab: novel B-cell depletion therapy for the treatment of rheumatoid arthritis.

Significant numbers of patients with rheumatoid arthritis (RA) suffer from disease that is refractory to both conventional therapy and newer biological agents such as TNF-alpha inhibitors. These patients may respond insufficiently, lose an effective response, develop toxicity or carry contraindications to such agents. Rituximab, a chimeric monoclonal antibody against CD20 that effectively depletes B cells in peripheral blood, has been licensed for the treatment of certain haematological malignancies for almost 10 years.