The latest advances in the use of biological DMARDs to treat Still's disease.

INTRODUCTION: Currently, the therapeutic management of Still's disease, a multisystemic inflammatory rare disorder, is directed to target the inflammatory symptoms and signs of patients. The treatment varies from glucocorticoids to disease-modifying antirheumatic drugs (DMARDs), both conventional synthetic and biological (bDMARDs). Usually, in refractory patients, bDMARDs are administered. AREAS COVERED: Among bDMARDs, IL-1 and IL-6 inhibitors are frequently used, as data reported from both clinical trials and 'real-life' experiences. Recently, innovative therapeutic strategies have suggested an early administration of bDMARDs to increase the rate of clinical response and drug-free remission. Some new targets have been also proposed targeting IL-18, IFN-γ, and JAK/STAT pathway, which could be applied to Still's disease and its life-threatening evolution. EXPERT OPINION: Many lines of evidence improved the knowledge about the therapeutic management of Still's disease with bDMARDs. However, many unmet needs may be still highlighted which could provide the basis to arrange further specific research in increasing the rate of clinical response. In fact, Still's disease remains a highly heterogeneous disease suggesting possible diverse underlying pathogenic mechanisms, at least partially, and consequent different therapeutic strategies. A better patient stratification may help in arranging specific studies to improve the long-term outcome of Still's disease.

Management and treatment of children, young people and adults with systemic lupus erythematosus: British Society for Rheumatology guideline scope.

The objective of this guideline is to provide up-to-date, evidence-based recommendations for the management of SLE that builds upon the existing treatment guideline for adults living with SLE published in 2017. This will incorporate advances in the assessment, diagnosis, monitoring, non-pharmacological and pharmacological management of SLE. General approaches to management as well as organ-specific treatment, including lupus nephritis and cutaneous lupus, will be covered. This will be the first guideline in SLE using a whole life course approach from childhood through adolescence and adulthood. The guideline will be developed with people with SLE as an important target audience in addition to healthcare professionals. It will include guidance related to emerging approved therapies and account for National Institute for Health and Care Excellence Technology Appraisals, National Health Service England clinical commissioning policies and national guidance relevant to SLE. The guideline will be developed using the methods and rigorous processes outlined in 'Creating Clinical Guidelines: Our Protocol' by the British Society for Rheumatology.

Cardiovascular risk of Janus kinase inhibitors compared with biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis without underlying cardiovascular diseases: a nationwide cohort study.

Objectives: Despite the ethnic differences in cardiovascular (CV) risks and recent increase in the prescription of Janus kinase (JAK) inhibitors, limited evidence is available for their CV outcomes in Asian patients with rheumatoid arthritis (RA). We aimed to compare the major adverse CV events (MACEs) of JAK inhibitors to those of biologic disease-modifying antirheumatic drugs (bDMARDs) in Korean patients with RA without baseline CV disease (CVD). Methods: In a nationwide retrospective cohort study, patients newly diagnosed with RA without a history of CVD between 2013 and 2018 were identified using the National Health Insurance Service database. The cohort was followed up until the end of 2019 for the development of MACEs. Hazard ratios (HRs) for MACEs such as myocardial infarction, stroke, coronary revascularization, or all-cause death, were estimated using Cox proportional hazard regression in a propensity score-matched cohort. Results: In total, 4,230 matched patients with RA were included (846 JAK inhibitor users and 3,384 bDMARD users). The crude incidence rate (95% confidence intervals, CI) per 100 patient-years for MACEs was 0.83 (0.31-1.81) and 0.74 (0.53-1.02) in the JAK inhibitor and bDMARD groups, respectively. The risk of MACEs was not significantly different between JAK inhibitor and bDMARD users with an adjusted HR (95% CI) of 1.28 (0.53-3.11). There were no significant differences in the risk of MACEs between JAK inhibitors and bDMARDs in each subgroup according to the types of bDMARDs, age, sex, Charlson comorbidity index score, and comorbidities. Conclusion: Compared to bDMARDs, JAK inhibitors were not associated with the occurrence of MACEs in Korean patients with RA without a history of CVD.

A Model to Predict Future Biologic or Targeted Synthetic DMARD Switch at a Subsequent Clinic Visit in Rheumatoid Arthritis.

INTRODUCTION: To understand factors leading to biologic switches and to develop a readily usable model with data collected in clinical care at preceding visits, with the overall aim to predict the probability of switching biologic at a subsequent clinic visit in patients with rheumatoid arthritis (RA). METHODS: Participants were adults with RA participating in the CorEvitas RA registry. The study matched patients who switched biologics or targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) with control patients who had not switched biologics/tsDMARDs; the cohort was divided into a training and test set for prediction model development and validation. Using the training set, the best subset regression, lasso, and elastic net methods were used to determine the best potential models. Area under the ROC curve (AUC) was used for the final selection of the best model, and estimated coefficients of this model were applied to the test dataset to predict switching. RESULTS: A total of 5050 patients were included, of whom 3016 were in the training set and 2034 were in the test dataset. The average age was 59.6 years, the majority were female (3998, 79.2%), and the average duration of RA at the time of switch or control visit was 12.8 years. The final model included prior Clinical Disease Activity Index (CDAI) by category, prior patient pain measurement, change in CDAI from baseline, age group, and number of prior biologics, all of which were significantly associated with switching biologics. The AUC was 0.690 for this model with the training dataset. The model was then applied to the test data with similar performance; the AUC was 0.687. CONCLUSION: We have developed a simple model to determine the probability of switching biologics for RA at the following clinic visit. This model could be used in practice to provide clinicians with more information about their patient's trajectory and likelihood of switching to a new biologic.

Prescription Trends of Biologic DMARDs in Treating Rheumatologic Diseases: Changes of Medication Availability in COVID-19.

Biologic disease-modifying antirheumatic drugs (DMARDs) are very effective in treating rheumatic diseases with a good patient tolerance. However, high cost and individualistic approach requires dedication of the physician. Therefore, the aim of this study was to determine how the COVID-19 pandemic has affected the prescription of biologic DMARDs in rheumatology at the University Hospital of Split. The data collection was conducted through an archive search in the Outpatient Clinic for Rheumatology in the University Hospital of Split, Split, Croatia. The search included the period before and after the start of the COVID-19 pandemic in Croatia (31 March 2020). Collected data included age, sex, ICD-10 code of diagnosis, generic and brand name of the prescribed drug, date of therapy initiation, and medication administration route. In the pre-COVID-19 period, 209 patients were processed, while in the COVID-19 period, 185 patients were processed (11.5% fewer). During pre-COVID-19, 231 biologic medications were prescribed, while during COVID-19, 204. During COVID-19, IL-6 inhibitors were less prescribed (48 (21%) vs. 21 (10%) prescriptions, p = 0.003), while IL-17A inhibitors were more prescribed (39 (17%) vs. 61 (30%) prescriptions, p = 0.001). In ankylosing spondylitis (AS), adalimumab was prescribed more during pre-COVID-19 (25 vs. 15 patients, p = 0.010), while ixekizumab was prescribed less (1 vs. 10 patients, p = 0.009). In rheumatoid arthritis, tocilizumab was prescribed more in the pre-COVID-19 period (34 vs. 10 patients, p = 0.012). Overall, the prescription trends of biologic DMARDs for rheumatologic diseases did not vary significantly in the University Hospital of Split, Croatia. Tocilizumab was prescribed less during COVID-19 due to shortages, while ixekizumab was more prescribed during COVID-19 due to an increase in psoriatic arthritis patients processed and due to being approved for treating AS.

Cost-utility analysis of biologic disease-modifying antirheumatic drugs (bDMARDs), targeted synthetic DMARDs (tsDMARDs) and biosimilar DMARDs (bsDMARDs) combined with methotrexate for Thai rheumatoid arthritis patients with high disease activity.

BACKGROUND: New biologic disease-modifying antirheumatic drugs (bDMARDs), targeted synthetic DMARDs (tsDMARDs) and biosimilar DMARDs (bsDMARDs) all showed greater clinical benefits in the treatment of patients with rheumatoid arthritis (RA) with high disease activity, but imposed higher costs than standard treatment. This study evaluated the cost-effectiveness of 11 alternative treatment strategies for RA patients with high disease activity whose treatment with three conventional synthetic DMARDs (csDMARDs) failed. METHODS: A Markov model was constructed using a societal perspective to estimate relevant costs and health outcomes in terms of quality-adjusted life years (QALYs) for a lifetime horizon (100 years), given a 3% annual discount. Alternative treatment strategies including five bDMARDs, two tsDMARDs, and four bsDMARDs in combination with methotrexate (MTX) were compared with the standard of care (SoC), i.e., cyclosporine and azathioprine. Direct and non-medical care costs were estimated by identifying the resources used, then multiplied by the standard costing menu in the year 2022. Utility and transitional probabilities were collected in three advanced tertiary hospitals. A network meta-analysis was used to estimate the efficacy of each treatment. Lifetime cost, QALYs and an incremental cost-effectiveness ratio were calculated and compared to the cost-effectiveness threshold of 160,000 THB per QALY gained (US $4,634, where 1 USD = 34.53 THB in 2022). Probabilistic and one-way sensitivity analyses were performed to estimate parameter uncertainties. RESULTS: The bDMARDs, tsDMARDs or bsDMARDs combined with MTX provided 0.09 to 0.33 QALYs gained with additional costs of 550,986 to 2,096,744 THB (US $15,957 to $60,722) compared to the SoC. The ICER ranged from 2.3 to 8.1 million THB per QALY (US $65,935 to $234,996) compared to the SoC. None of these combinations was cost-effective in the Thai context. The results were sensitive to the mortality hazard ratio of patients with high disease activity. CONCLUSIONS: Combinations of MTX with either bDMARDs, tsDMARDs or bsDMARDs were not economically attractive compared to the standard practice. However, they reduced disease activity and improved patient quality of life. The price negotiation process for these treatments must be conducted to ensure their financial value and affordability before they are included in the pharmaceutical reimbursement list.

Comparative Efficacy of Biologic Disease-Modifying Anti-Rheumatic Drugs for Non-Radiographic Axial Spondyloarthritis: A Systematic Literature Review and Bucher Indirect Comparisons.

INTRODUCTION: Biologic disease-modifying anti-rheumatic drugs (bDMARDs), including certolizumab pegol (CZP), are effective treatment options for the management of non-radiographic spondyloarthritis (nr-axSpA). In the absence of head-to-head comparisons in nr-axSpA, we conducted a systematic literature review (SLR) and indirect treatment comparison (ITC) to better understand the comparative efficacy of CZP vs. other bDMARDs. METHODS: Literature searches were conducted in October 2020 in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in patients with nr-axSpA who had failed at least one non-steroidal anti-inflammatory drug and were treated with bDMARDs. Outcomes of interest included the Assessment of Spondyloarthritis international Society (ASAS), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and Disease Activity Index (BASDAI), and spinal pain score. Comparative efficacy was examined using a series of Bucher ITCs in subgroups matched by prior exposure to bDMARDs, disease duration, baseline C-reactive protein (CRP) levels/magnetic resonance imaging (MRI) status, and timepoints, to ensure comparability between studies. RESULTS: At 12-16 weeks, treatment with CZP was significantly more likely to achieve ASAS20/40 response and ASDAS-inactive disease status vs. etanercept (ETN), ixekizumab (IXE), and secukinumab (SEC). CZP showed statistically significant improvement in BASDAI, BASFI, and total spine pain score over adalimumab (ADA), ETN, and IXE, and in BASFI over SEC. Among patients with objective signs of inflammation (OSI; elevated CRP levels and/or inflammation on MRI at baseline), CZP had a statistically significant advantage over ETN and SEC (with or without loading dose) in achieving ASAS40, whereas the comparisons with other bDMARDs did not show any statistically significant differences. CONCLUSION: In the overall matched population, CZP performed significantly better than most comparators in improving the clinical outcomes. Among patients with OSI, CZP was found to be superior to SEC (in the MRI-/CRP + and MRI + /CRP- subgroups) and ETN (in the MRI + /CRP- subgroup) and it was comparable to golimumab and IXE across the different OSI subgroups.

Five cases of seronegative persistent inflammatory monoarthritis improved with biological therapy.

Persistent inflammatory monoarthritis is defined as inflammation of one joint that continues for longer than 3 months. Most cases remain as nonspecific arthritis after several years. Persistent inflammatory monoarthritis is difficult to diagnose and treat in the early stage because there are no criteria for diagnosis and treatment. We report five seronegative persistent inflammatory monoarthritis cases that affected the left knee, right knee, left knee, left ankle, and right knee. All patients underwent joint punctures; two patients received steroid injections in the affected joint. The bacterial and mycobacterial culture were negative in all patients. Two patients received oral steroids, and two patients were administered nonsteroidal anti-inflammatory drugs; however, their symptoms did not improve, and one patient experienced progression of joint destruction. We investigated the usefulness of biological disease-modifying antirheumatic drugs for the treatment of seronegative persistent inflammatory monoarthritis. We obtained a remarkable improvement effect and prevented the advance of joint destruction.

Choosing the Appropriate Target for the Treatment of Psoriatic Arthritis: TNFα, IL-17, IL-23 or JAK Inhibitors?

Psoriatic arthritis (PsA) is a highly heterogenous disease. Apart from arthritis and psoriasis, other manifestations can also occur, including enthesitis, dactylitis, axial-, nail-, eye- and bowel- involvement. Comorbidities are also frequent in the setting of PsA, with cardiovascular disease and mental-health disorders being the most frequent. The Rheumatologist's arsenal has many different treatment options for treating PsA. Despite their effectiveness, there are some differences in terms of efficacy and safety that might affect clinician's decision for one or the other drug. Comparing biologic DMARDs and JAK-inhibitors, one could say that they have similar effectiveness in terms of musculoskeletal manifestations. However, anti-IL-17 and anti-IL-23 drugs seem to be more effective for skin manifestations. In contrast, JAK-inhibitors and etanercept might be less effective for these manifestations. Inflammatory bowel disease and uveitis are non-responsive to etanercept and anti-IL-17 drugs. As regards to comorbidities, data are scarce, but future studies will shed light on possible differential effect of bDMARDs or JAK-inhibitors. Safety is always an important drive for choosing the appropriate treatment. Infections are the most common adverse event of these drugs. Etanercept and anti-IL-17 drugs are safer for patients having latent tuberculosis, while herpes zoster is more common in individuals receiving JAK-inhibitors. Finally, venous thromboembolism risk, should be taken into account when JAK-inhibitors are used. In this review, we comparatively present, as outlined above, the various aspects that could affect the choice of the appropriate bDMARD or JAK-inhibitor for the treatment of a PsA patient.

Recent issues in JAK inhibitor safety: perspective for the clinician.

INTRODUCTION: Five jakinibs are approved for the treatment of rheumatic diseases. There has been a question of their relative safety to other medications since their approval. AREAS COVERED: A literature search was conducted in Pub Med for the integrated safety databases of these molecules in their clinical trial program, registries, and insurance claims data and in a prospective head-to-head study compared to tumor necrosis factor inhibitors in a high-risk population for cardiovascular and malignancy events. There were no differences found in the safety databases, registries or insurance claims data indicating jakinibs are more likely to cause major adverse cardiac events, malignancy, venous thrombotic episodes, infections, and mortality compared to other medications. The head-to-head trial found that there were numerically more of these events with the jakinib compared to tumor necrosis factor inhibitors. EXPERT OPINION: Cardiac events and malignancy occur more frequently in rheumatoid patients with active disease. Although the safety databases, claims data, and registries suggest that there is no difference in the risks with a jakinib versus biologics, the prospective safety study showed these events occur numerically higher in patients at the highest risk for these events. In this population, one should consider using a biologic before a jakinib.

Current Management of Trigger Digit in Rheumatoid Arthritis Patients: A Survey of ASSH Members.

BACKGROUND: Traditional dogma regarding management of rheumatoid arthritis (RA) patients with trigger digit symptoms holds that A1 pulley release should be avoided. Surgical release was thought to further destabilize the metacarpophalangeal joint. Biologic disease modifying anti-rheumatic drugs (DMARDs) have limited the development of hand deformities. Despite advances in RA treatment, many textbooks continue to discourage release of the A1 pulley in RA patients. The aim of this study was to determine if this belief is consistent with current trends in surgical management of trigger digits in patients with RA. METHODS: Active Members of the American Society for Surgery of the Hand (ASSH) were surveyed on their training and current practices as related to RA patients with trigger digits. RESULTS: Five hundred three surveys were completed (16% response rate). During training, 55% of ASSH Members were taught to avoid releasing the A1 pulley in RA patients. Seventy-one percent of respondents currently release the A1 pulley in RA patients with no preexisting deformities, no tenosynovial thickening, or if tenosynovectomy and flexor digitorum superficialis slip excision fail to relieve triggering. Forty percent reported that their practice has evolved toward more frequent release of the A1 pulley in RA patients. CONCLUSION: The majority of ASSH Active Members were taught during training to avoid surgical release of the A1 pulley in RA patients to prevent acceleration of finger deformities. Indications and contraindications for A1 pulley release are evolving along with the improved natural history of RA associated with the use of biologic DMARDs.

Real-Life Retention Rates and Reasons for Switching of Biological DMARDs in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis.

Aims: To determine real-life biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) retention rates in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), explore reasons for switching and to compare results to previously published data. Methods: Time-to-event analysis for mean treatment duration (estimated as the Restricted Mean Survival Time), b/tsDMARD failure, and b/tsDMARDs switching was performed for 230 patients (n = 147 RA, 46 PsA, 37 AS) who commenced their first b/tsDMARD between 2008 and 2018. Patients were managed in a dedicated "biologics" clinic in a tertiary hospital; the choice of b/tsDMARD was clinician driven based on medical factors and patient preferences. The effect of covariates on switching risk was analysed by a conditional risk-set Cox proportional-hazards model. Treatment retention data was compared to a historical analysis (2002-2008). Results: The proportions remaining on treatment (retention) were similar, throughout follow-up, for the first, second and third b/tsDMARDs across all patients (p = 0.46). When compared to RA patients, the risk of b/tsDMARD failure was halved in PsA patients [Hazard Ratio (HR) = 0.50], but no different in AS patients (HR = 1.0). The respective restricted mean (95%CI) treatment durations, estimated at 5 years of follow-up, were 3.1 (2.9, 3.4), 4.1 (3.7, 4.6), and 3.3 (2.8, 3.9) years, for RA, PsA, and AS, respectively. Age, gender, disease duration, smoking status and the use of concomitant csDMARDS were not associated with the risk of bDMARD failure. The most common reasons for switching in the first and subsequent years were secondary (n = 62) and primary (n = 35) failure. Comparison with historical data indicated no substantive differences in switching of the first biologic for RA and PsA. Conclusion: Similar retention rates of the second and third compared to the first b/tsDMARD in RA, PsA, and AS support a strategy of differential b/tsDMARDs use informed by patient presentation. Despite greater availability of b/tsDMARDs with differing mechanisms of action, retention rates of the first b/tsDMARD remain similar to previous years.

Biologic and Targeted Synthetic DMARD Utilization in the United States: Adelphi Real World Disease Specific Programme for Rheumatoid Arthritis.

INTRODUCTION: In patients with inadequate response or intolerance to first biologic disease-modifying antirheumatic drug (bDMARD), guidelines recommend switching to an agent of different mechanism of action or to another bDMARD. However, the reasons behind switching between bDMARD/targeted synthetic (ts)DMARD are not well documented in many studies. The objective of this study was to assess the rheumatologists' perceptions and behaviors towards choice of initial b/tsDMARD treatment and reasons for switching between bDMARDs/tsDMARDs, in the context of present treatment patterns. METHODS: This was a retrospective analysis of data collected from the 12th Adelphi Real World Disease Specific Programme for rheumatoid arthritis (RA). Qualified rheumatologists involved in treatment decision-making for ≥ 10 patients a month completed patient record forms (PRFs). Patients aged ≥ 18 years with RA diagnosis and receiving bDMARD/tsDMARD were included. The outcomes assessed were proportion of patients receiving bDMARD/tsDMARD at molecule and class levels; rheumatologist-reported reasons for choice of therapy; proportion of patients who switched bDMARDs/tsDMARDs; and rheumatologist-reported reasons for switching therapies. RESULTS: Eighty-six rheumatologists completed PRFs for 1027 patients. Of these, 621 were receiving bDMARD/tsDMARD at data collection. The majority (73%) of patients received first-line bDMARD/tsDMARD, and at first-line, 68% received a tumor necrosis factor inhibitor (TNFi) and 21% received a Janus kinase inhibitor (JAKi). The response option of strong overall efficacy was the primary reason for selecting first-line and second-line bDMARD/tsDMARD. A total of 163 patients had switched from first-line b/tsDMARD to second-line b/tsDMARD therapy. Of these, 44, 28, and 17% had switched from TNFi to another TNFi, TNFi to non-TNF biologic, and TNFi to JAKi, respectively. Lack of efficacy and worsening disease were the most frequent reasons for switching therapies. CONCLUSIONS: TNFis remain the most prescribed b/tsDMARD for first-line and second-line treatments. Strong overall efficacy was the primary reason for selecting therapy and loss of efficacy was the primary reason for switching therapy.

COVID-19 Among Patients With Inflammatory Rheumatic Diseases.

BACKGROUND: The course of novel coronavirus disease 2019 (COVID-19) has been of special concern in patients with inflammatory rheumatic diseases (IRDs) due to the immune dysregulation that may be associated with these diseases and the medications used for IRDs, that may affect innate immune responses. OBJECTIVE: In this cohort study, we aimed to report the disease characteristics and variables associated with COVID-19 outcome among Turkish patients with IRDs. METHODS: Between April and June, 2020, 167 adult IRD patients with COVID-19 were registered from 31 centers in 14 cities in Turkey. Disease outcome was classified in 4 categories; (i) outpatient management, (ii) hospitalization without oxygen requirement, (iii) hospitalization with oxygen requirement, and (iv) intensive care unit (ICU) admission or death. Multivariable ordinal logistic regression analysis was conducted to determine variables associated with a worse outcome. RESULTS: 165 patients (mean age: 50 ± 15.6 years, 58.2% female) were included. Twenty-four patients (14.5%) recovered under outpatient management, 141 (85.5%) were hospitalized, 49 (30%) required inpatient oxygen support, 22 (13%) were treated in the ICU (17 received invasive mechanic ventilation) and 16 (10%) died. Glucocorticoid use (OR: 4.53, 95%CI 1.65-12.76), chronic kidney disease (OR: 12.8, 95%CI 2.25-103.5), pulmonary disease (OR: 2.66, 95%CI 1.08-6.61) and obesity (OR: 3.7, 95%CI 1.01-13.87) were associated with a worse outcome. Biologic disease-modifying antirheumatic drugs (DMARDs) do not seem to affect COVID-19 outcome while conventional synthetic DMARDs may have a protective effect (OR: 0.36, 95%CI 0.17-0.75). Estimates for the associations between IRD diagnoses and outcome were inconclusive. CONCLUSIONS: Among IRD patients with COVID-19, comorbidities and glucocorticoid use were associated with a worse outcome, while biologic DMARDs do not seem to be associated with a worse outcome.

Preferences of inflammatory arthritis patients for biological disease-modifying antirheumatic drugs in the first 100 days of the COVID-19 pandemic

Background/aim: To evaluate treatment adherence and predictors of drug discontinuation among patients with inflammatory arthritis receiving bDMARDs within the first 100 days after the announcement of the COVID-19 pandemic. Materials and methods: A total of 1871 patients recorded in TReasure registry for whom advanced therapy was prescribed for rheumatoid arthritis (RA) or spondyloarthritis (SpA) within the 3 months (6­9 months for rituximab) before the declaration of COVID-19 pandemic were evaluated, and 1394 (74.5%) responded to the phone survey. Patients' data regarding demographic, clinical characteristics and disease activity before the pandemic were recorded. The patients were inquired about the diagnosis of COVID-19, the rate of continuation on bDMARDs, the reasons for treatment discontinuation, if any, and the current general disease activity (visual analog scale, [VAS]). Results: A total of 1394 patients (493 RA [47.3% on anti-TNF] patients and 901 SpA [90.0% on anti-TNF] patients) were included in the study. Overall, 2.8% of the patients had symptoms suggesting COVID-19, and 2 (0.15%) patients had PCR-confirmed COVID-19. Overall, 18.1% of all patients (13.8% of the RA and 20.5% of the SpA; p = 0.003) discontinued their bDMARDs. In the SpA group, the patients who discontinued bDMARDs were younger (40 [21­73] vs. 44 years [20­79]; p = 0.005) and had higher general disease activity; however, no difference was relevant for RA patients. Conclusion: Although the COVID-19 was quite uncommon in the first 100 days of the pandemic, nearly one-fifth of the patients discontinued bDMARDs within this period. The long-term effects of the pandemic should be monitored.

Effectiveness and safety of treat-to-target strategy in elderly-onset rheumatoid arthritis: a 3-year prospective observational study.

OBJECTIVES: To evaluate 3-year outcomes of following a treat-to-target (T2T) strategy targeting low disease activity for patients with elderly-onset RA (EORA) and to confirm safety profile of T2T. METHODS: Treatment was adjusted to target low disease activity with conventional synthetic DMARDs, followed by biologic DMARDs (bDMARDs) in 197 MTX-naïve EORA patients (mean age 74.9 years) with moderate-to-high disease activity. Non-implementation of T2T was evaluated at week 12, 24, 36, 52, 76, 104 and 128. To evaluate risks of using MTX, bDMARDs and glucocorticoids, 2122 periods of 3 months each were analysed using Bayesian hierarchical logistic regression models. RESULTS: Of the patients, 84.7% received methotrexate, 34.0% glucocorticoids with DMARDs and 41.6% bDMARDs during the observation period. Sixty-nine of the 197 patients failed to adhere to T2T because of comorbidities or the patient's own decision: 33 failed once, 19 twice, 10 three times and 6 four times or more. Simplified disease activity index (SDAI) remission and HAQ Disability Index (HAQ-DI) ≤0.5 at 3 years were achieved in 57.8% and 70.3% of the 128 patients adhering to T2T, and 34.8% and 43.5% of the 69 patients who did not adhere to T2T, respectively, and these were significantly different. Eighty-nine serious adverse events (SAEs) of any type were reported in 61 patients. MTX, bDMARDs and glucocorticoid were not associated with SAEs when adjusted for mean SDAI during the observation period and comorbidities at baseline. CONCLUSION: T2T strategy for EORA by using MTX and bDMARDs was effective with an acceptable safety profile. Adhering to T2T led to better outcomes.

Treatment strategies in axial spondyloarthritis: what, when and how?

There have been major advances in the management of axial spondyloarthritis (axSpA) with the introduction of effective biologic agents targeting TNF and IL-17A. Clinicians now have more choice but, despite treatment recommendations, are still faced with significant uncertainty when deciding on the optimal treatment strategy for an individual patient in clinical practice. Management of axSpA typically requires both non-pharmacological and pharmacological interventions. NSAIDs remain the first line drug therapies for axSpA with proven efficacy for symptomatic management but uncertainty remains regarding their optimal long-term use relating to radiographic progression and safety in axSpA. To-date there are no head-to-head trials of biologics in axSpA. Clinicians need to consider other factors, including extra-articular manifestations, comorbidities, safety and radiographic progression when deciding on which biologic to recommend for an individual patient. This article will explore the evidence relating to these factors and highlight areas of unmet need.

Real-World Analysis of Therapeutic Patterns in Patients Affected by Rheumatoid Arthritis in Italy: A Focus on Baricitinib.

INTRODUCTION: The objective of this study was to evaluate treatment patterns in patients with rheumatoid arthritis (RA), with a focus on the utilization of baricitinib, an oral highly selective Janus kinase 1 and 2 inhibitor, in an Italian real-world setting. METHODS: This observational retrospective analysis was based on data collected in selected Italian administrative databases. Patients aged ≥ 18 years with a diagnosis of RA defined by hospitalization discharge diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 714.0) or by disease exemption code 006 for RA in 2018 were included. The index date (ID) was defined as the date of first prescription for a drug indicated for RA during the inclusion period. Patients without a prescription for biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) before the ID were considered to be b/tsDMARD naïve. A further analysis was performed on patients only receiving baricitinib. RESULTS: A total of 41,290 RA patients were enrolled, of whom 55.6% were not treated with conventional synthetic DMARDs (csDMARDs) or b/tsDMARDs, 39.4% were receiving therapy with csDMARDs, and 5.0% were using b/tsDMARDs. In the latter group, 2.7% (n = 56) were receiving therapy with baricitinib. In 2018, 13.2% of csDMARD-treated patients switched to b/tsDMARDs, of whom 4.3% (n = 93) of these switched to baricitinib. In total, 149 patients (mean age ± standard deviation 57.6 ± 12.1; 12.8% male) had a baricitinib prescription, of whom 51% were b/tsDMARD naïve. At baseline, 61.7% of baricitinib users were receiving combination therapy with csDMARDs plus corticosteroids, 26.2% were receiving combination therapy with corticosteroids, and 8.1% were receiving combination therapy with csDMARDs; 4% were receiving baricitinib monotherapy. During follow-up, the proportion of patients receiving baricitinib monotherapy increased to 38.9%, while 26.9, 18.8, and 15.4% of baricitinib users received combination therapy with corticosteroids, csDMARDs plus corticosteroids, and csDMARDs, respectively. CONCLUSION: This study provides a current view of the treatment patterns in Italian patients with RA in a real-world setting of daily clinical practice, with a focus on baricitinib utilization.

Background Glucocorticoid Therapy Has No Impact on Efficacy and Safety of Abatacept or Adalimumab in Patients with Rheumatoid Arthritis.

To date, the impact of background glucocorticoids (GC) on the efficacy and safety of abatacept or adalimumab in patients with active rheumatoid arthritis (RA) is not clearly established. This post hoc analysis of (AMPLE) trial (NCT00929864) compared efficacy and safety outcomes over 2 years in patients treated with abatacept or adalimumab plus background methotrexate (MTX), who continued GC (≤10 mg/day) versus those who were not receiving GC (no-GC). Of 646 randomized patients, 317 received abatacept + MTX (161 GC, 156 no-GC) and 326 received adalimumab + MTX (162 GC, 164 no-GC). At Year 2, the adjusted mean changes from baseline in Disease Activity Score (DAS28 C-reactive protein (CRP)) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were not significantly different in the GC versus no-GC subgroups receiving abatacept or adalimumab. A similar proportion of patients achieved remission, HAQ-DI score improvement ≥0.3 and radiographic progression rates. No clinically meaningful safety differences were observed between GC versus no-GC subgroups either with abatacept or adalimumab. In patients with active RA of similar baseline disease activity treated with abatacept or adalimumab plus background MTX, there was no additional value of background GC on clinical, functional or radiographic outcomes over two years.