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Introduction: Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week 24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or psoriasis at baseline. Methods: This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W). Efficacy outcomes were analyzed through week 24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA < 3%, moderate = 3% ≤ BSA ≤ 10%, severe = BSA > 10%. The primary outcomes assessed were the proportion of patients achieving American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. Secondary outcomes included musculoskeletal, disease activity, skin and nail, and health-related quality-of-life measures. Results: Similar proportions of patients achieved ACR20/ACR50/ACR70 over time across all severity subgroups and treatment arms. More than one-third of IXE-treated patients achieved ACR20 at week 4, or ACR50 at week 24, with no significant differences according to psoriasis severity at baseline. Disease activity outcomes were similar through week 24 with both IXEQ4W and IXEQ2W, regardless of psoriasis severity at baseline. There were no significant differences over 24 weeks in the proportions of IXE-treated patients with mild, moderate, or severe baseline psoriasis who achieved Minimal Disease Activity (MDA). Across all severity subgroups, IXE demonstrated Psoriasis Area Severity Index 100 response as early as week 4, and approximately one-third of IXE-treated patients achieved total skin clearance at week 24. Conclusion: IXE demonstrated rapid and consistent efficacy in joint, skin, and nail for patients with PsA, regardless of baseline psoriasis severity. Trial Registration: SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To evaluate the drug treatment trends in patients with incident juvenile idiopathic arthritis (JIA) in 2006–2014. In Finland, patients are entitled to a special reimbursement for medication if their condition meets certain criteria. We gathered all reimbursement decisions with the ICD-10 diagnosis of M08 for patients under 16 years of age from a nationwide register maintained by Kela, the Social Institution of Finland. A total of 2439 incident cases of JIA were identified. We surveyed their reimbursable drugs purchased for the first time for JIA upon a doctor's prescription in 3-year cohorts (2006–2008, 2009–2011, 2012–2014). Changes of drug treatment for JIA became more active during our study years. Between 2006–2008 and 2011–2014, the introduction of methotrexate (MTX) for the first time within the first 3 months increased from 73% (2006–2008) to 90% (2011–2014) of the patients, IRR (incidence rate ratio) was 1.23 (95% CI 1.10–1.37). The use of parenteral MTX increased even more; IRR was 1.97 (95% CI 1.61–2.41). During the first 2 years of their disease, 18% of the first cohort received subcutaneous biologic agents, while the corresponding proportion in the last cohort was 31%. Biologic agents were more likely to be introduced for patients with early (3 months) MTX administration than for patients without early MTX introduction; HR (hazard ratio) 2.19 (95% CI 1.63–2.93). During the follow-up, MTX administration became more prevalent for the treatment of JIA soon after diagnosis, mostly because of the increase in the use of parenteral MTX. Key Points • The drug therapy for treating juvenile idiopathic arthritis has changed during recent years. • Methotrexate, some other conventional DMARDs, and biologic DMARDs are introduced earlier. [ABSTRACT FROM AUTHOR]

Purpose of Review: Psoriatic arthritis (PsA) is an immune-mediated systemic inflammatory disorder with heterogeneous clinical features. Treatment for PsA has progressed rapidly, especially over the past two decades. Herein we review relevant studies and key developments in treatment options for PsA from the past 5 years. Recent Findings: Conventional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate showed some efficacy for several domains of PsA, albeit less than that achieved with TNF inhibitors (TNFi). TNFi have been shown to be efficacious in treatment across all domains of PsA, particularly preventing radiographic damage, and are highly efficient early in the disease course. Inhibitors of IL-12/23, IL-17A, IL-23, phosphodiesterase 4, T cell costimulation, and janus kinases (JAK) have proven efficacious in the treatment of peripheral arthritis of PsA patients. The introduction of biosimilars to TNFi is expected to impact the treatment algorithm for PsA treatment by increasing access to biologic drugs. Newer treatment modalities including IL-23-specific inhibitors, IL-17A and IL-17F dual inhibitors, and jakinibs (janus kinase inhibitors) with different specificity are currently being developed for treatment of PsA. Summary: The recent development of new therapeutic agents for PsA has led to better control of PsA across all of its disease domains. The future of PsA management will likely usher in treatment with different mechanisms of action, allow for more access to care, and hopefully see the possibility of precision medicine to help select the optimal treatment approach for individual PsA patients. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) reactivation is a common complication of immunosuppressive treatment in high prevalence countries. Biological disease-modifying antirheumatic drugs (bDMARDs) cause this adverse event more often than conventional immunosuppressants. The incidence of HBV reactivation during treatment for rheumatic diseases in Germany is unclear. Furthermore, it remains open how to treat and monitor patients at risk during immunosuppressive therapy with bDMARDs. We examined 2054 patients from a German tertiary rheumatology center in order to analyze the prevalence of HBc-antibody-positivity and the incidence of HBV reactivation in German rheumatology patients treated with immunosuppressants. Of 1317 patients treated with bDMARDs and 737 conventional synthetic DMARD (csDMARDs) patients between 2008 and 2017, 86 had a history of HBV infection (anti-HBc positive). Only two patients were suffering from chronic infection (HBsAg positive). Three patients were treated pre-emptively with entecavir, and eight patients after HBV DNA reappearance. No liver failure occurred due to HBV reactivation. Compared to anti-HBc-positive patients without reactivation, the reactivation group included more patients exposed to three or more classes of bDMARDs (p = 0.017). The median HBs antibody titer was significantly lower in the reactivation group (15.0 IU/l vs. 293.5 IU/l; p = 0.001). This study shows that bDMARDs and csDMARDs can safely be administered to patients with a history of HBV, provided they are closely monitored. Low titers of anti-HBs antibodies and a history of ≥ 3 classes of immunosuppressants increase the risk of HBV reactivation. These data highlight major differences to high prevalence regions. [ABSTRACT FROM AUTHOR]

To compare the characteristics of rheumatoid arthritis (RA) patients receiving either biosimilar or originator infliximab and to identify the effectiveness and safety of biosimilar infliximab in RA patients in real-world practice. RA patients who started either biosimilar or originator infliximab were selected using the prospective biologic disease-modifying anti-rheumatic drugs (DMARDs) registry: BIOlogics Pharmacoepidemiologic StudY (BIOPSY). Baseline characteristics of the two groups were compared, and short-term treatment outcomes, including DAS28-ESR and HAQ-DI scores, were compared after initiation of biosimilar or originator infliximab. The drug retention rates of the two groups were also compared. A total of 100 RA patients, 55 biosimilar, and 45 originator infliximab users were included in this analysis. Baseline characteristics of age, disease duration, and previous or current medications were similar in the two groups. Baseline DAS28-ESR was higher in the originator infliximab group (6.3 ± 1.1 vs. 5.8 ± 1.1, p = 0.02). The early DAS28-ESR remission rates observed 7.9 ± 1.8 months after starting biosimilar and originator infliximab were 15.0 and 25.0%, respectively ( p = 0.47). The change in HAQ-DI did not differ between the two groups (0.4 ± 0.7 vs. 0.4 ± 0.8, p = 0.94). Patients treated with biosimilar infliximab in clinical practice had lower disease activity at the start of treatment than those receiving originator infliximab. Biosimilar infliximab was well-tolerated, safe, and of similar clinical effectiveness to originator infliximab. Larger number of patient and longer follow-up data will be needed to confirm the effectiveness and safety of biosimilar infliximab in clinical practice. [ABSTRACT FROM AUTHOR]

Patients with rheumatoid arthritis (RA) are at increased risk of infection. In this study, we determined the risk of and risk factors for Staphyococcus aureus ( S. aureus) sepsis in RA. We assembled a retrospective nested case-control subset of RA patients with S. aureus sepsis from the Barnes-Jewish Hospital Medical Informatics database, confirmed the diagnoses, and collected data electronically and by chart review. We used multivariate logistic regression to identify independent risk factors for S. aureus sepsis, with risk expressed as odds ratios (ORs). We extracted data on the length of hospitalization and 30-day and 1-year mortality from the Medical Informatics database for all cases and controls. There were 48 confirmed S. aureus sepsis cases and 232 confirmed controls in the RA cohort. In multivariate analysis, indwelling central venous catheter (OR 15.97; 95 % CI 5.09-50.10; p < 0.01) and congestive heart failure (OR 2.89; 95 % CI 1.26-6.63; p = 0.01) were independently associated with risk of S. aureus sepsis, while treatment with disease-modifying anti-rheumatic drugs (DMARDs), both biologic and non-biologic, was not. S. aureus sepsis was associated with increased 30-day and 1-year mortality (OR 7.37; 95 % CI 2.86-19.0; p < 0.01 for 30-day and OR 5.24; 95 % CI 2.51-10.94; p < 0.01 for 1-year mortality) and longer hospitalization ( p < 0.01). Treatment with biologic DMARDs was not associated with longer hospitalization ( p = 0.89). Indwelling central venous catheters and congestive heart failure increased the risk of S. aureus sepsis in this observational cohort of patients with RA. Treatment with biologic and non-biologic DMARDs did not increase this risk. [ABSTRACT FROM AUTHOR]

Biologic disease modifying anti-rheumatic drugs have transformed the management of rheumatoid arthritis (RA) since their introduction into clinical practice over a decade ago. Following large-scale clinical trials, a number of biologics, with different mechanisms of action, have been licensed for the condition. In this review, we will summarise the current evidence for biologic use in RA with an emphasis on their efficacy and tolerability. In addition, we will provide a commentary on the current limitations and unmet needs in this area and discuss the future of biologic intervention. [ABSTRACT FROM AUTHOR]