The Effect of Depression on Disease Activity and Treatment Response in Patients with Inflammatory Arthritis: Results from a Narrative Literature Review.

Background: Inflammatory arthritis refers to a group of diseases that have a common presentation of joint pain, stiffness, and inflammation. Meanwhile, major depressive disorder is a mental health disorder characterized by anhedonia and low mood. Inflammatory arthritis patients have high rates of major depressive disorder, estimated at being up to 38.8%. Depression leads to a significant reduction in patient's health-related quality of life, treatment adherence, and many other measures of health, both subjective and clinical. Purpose: This literature review explores the effect that depression has on treatment response for the drugs used in inflammatory arthritis. Methods: A systematic search using PubMed was conducted identifying articles which were each reviewed for relevance and eligibility. Results: Depression was negatively associated with treatment response to all classes of drugs used to manage inflammatory arthritis, with an increased disease activity and/or number of swollen/tender joints, as well as a reduced rate of remission being recorded for patients with depression compared to those without. However, this effect on treatment response was less clear when conventional synthetic Disease Modifying Anti-rheumatic Drugs were studied, possibly because their anti-inflammatory effects have wide impacts on the whole immune system, whereas biologic Disease Modifying Anti-rheumatic Drugs have very specific targets. Conclusion: Inflammatory arthritis patients have a significantly lowered response to most drugs when they have depression. Screening and treating depression may attenuate this association. It is recommended that further research focuses on screening for and treating depression in inflammatory arthritis patients.

Fertility issues in women of childbearing age with spondyloarthritis.

The topic of fertility in women with spondyloarthritis (SpA) has been scarcely investigated to date. Recent systematic reviews and registry studies have brought renewed attention to the plight of women of childbearing age with rheumatic diseases, in particular SpA. Fertility may be impacted by physical impairment, hormonal imbalances and psychological distress. Several studies observed a reduction in anti-Müllerian hormone in women with SpA, reflecting a reduced ovarian reserve (OR). Furthermore, disease activity and the use of certain therapies can alter fertility, and this is reflected in a prolonged time-to-pregnancy (TTP), a validated outcome measure that can evaluate the status of subfertility. The employment of glucocorticoids or non-steroidal anti-inflammatory drugs has also been linked to reduced fertility, whereas the use of biologics, especially tumour necrosis factor inhibitors (TNFi), is not associated with a prolonged TTP. In all women of childbearing age with rheumatic diseases, preconception counselling is paramount, and a referral to a reproductive specialist should be considered in the presence of multiple factors that may influence fertility. A comprehensive evaluation involving a multidisciplinary team of rheumatologists, gynaecologists, and often psychologists is warranted. In this narrative review, we collected the currently available literature focusing on fertility issues in women affected by SpA, providing data on fertility outcomes, hormonal imbalance, and therapeutic concerns.

Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 100-Week Results from the KEEPsAKE 2 Randomized Clinical Trial.

INTRODUCTION: Long-term therapeutic options providing durable response and tolerability are needed for psoriatic arthritis (PsA). The ongoing KEEPsAKE 2 trial is evaluating risankizumab treatment in patients with active PsA who previously had inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and/or 1-2 biologic DMARDs (bDMARD-IR). Herein, we report results through 100 weeks of treatment. METHODS: KEEPsAKE 2 is a global phase 3 trial. Patients with active PsA were randomized 1:1 to double-blind subcutaneous risankizumab 150 mg or placebo (weeks 0, 4, and 16). At week 24, all patients received open-label risankizumab every 12 weeks until end of study. Efficacy endpoints included achieving ≥ 20% improvement in PsA symptoms using American College of Rheumatology criteria (ACR20), attaining minimal disease activity (MDA; meeting ≥ 5/7 criteria of low disease activity and extent), and improving in other measures. RESULTS: At the cutoff date, 345/443 (77.9%) patients were ongoing in the study. ACR20 was achieved in 57.1% and 52.5% of the continuous risankizumab and placebo/risankizumab cohorts, respectively, at week 100 and in 60.0% and 55.8%, respectively, at week 52. In week 52 responders, maintenance of ACR20 at week 100 was achieved in 74.8% (continuous risankizumab) and 78.7% (placebo/risankizumab) of patients. In the continuous risankizumab and placebo/risankizumab cohorts, respectively, MDA was achieved by 33.0% and 33.3% of patients at week 100 and by 27.2% and 33.8% at week 52. Among MDA responders at week 52, maintenance of MDA response was achieved by 83.6% and 73.0% of the continuous risankizumab and placebo/risankizumab cohorts, respectively. Risankizumab was well tolerated through week 100. CONCLUSIONS: Risankizumab demonstrated durable efficacy and tolerability through 100 weeks; most patients who achieved ACR20 and MDA responses at week 52 maintained this achievement through week 100. There were no new safety signals in patients who had csDMARD-IR and bDMARD-IR. TRIAL REGISTRATION: ClinicalTrials.gov NCT03671148.

Risankizumab, a biologic disease-modifying antirheumatic drug, helps control the body's immune system to reduce symptoms of psoriatic arthritis (a disease that inflames the joints of people who have the skin condition psoriasis). The ongoing KEEPsAKE 2 study is evaluating how well risankizumab works and how safe it is for treating adult patients with active psoriatic arthritis who previously experienced inadequate response to one or more specific types of disease-modifying anti-arthritis drugs. Patients were randomly assigned to receive either risankizumab or an inactive drug; after 24 weeks, all patients received risankizumab. At study week 100, 57% of patients who were assigned to receive continuous risankizumab since the start of the study experienced a 20% or more improvement in a measure of psoriatic arthritis symptoms using criteria established by the American College of Rheumatology (ACR20); a similar proportion of patients achieved a 20% improvement at both weeks 24 and 52. Similarly, 56% and 53% of patients who switched from inactive drug to risankizumab achieved ACR20 at weeks 52 and 100 (more than before switching to risankizumab at week 24). Minimal disease activity (MDA) was evaluated by assessing joint and skin symptoms, affected body surface area, pain, and physical function. At week 100, 33% of patients achieved MDA (both groups), which was similar to week 52. Most patients who achieved ACR20 or MDA at week 52 maintained responses at week 100. Improvements with risankizumab were seen in several other measures of treatment outcomes through week 100. Risankizumab was generally safe through 100 weeks.

Impact of body composition on clinical outcomes in patients with active radiographic axial spondyloarthritis under biological therapy.

OBJECTIVE: To assess the association of body composition, evaluated by bioimpedance analysis (BIA), with disease activity, physical function, and mobility in patients with axSpA undergoing bDMARD treatment for one year. METHODS: Patients with AS (radiographic axSpA) were enrolled in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to be candidates for bDMARD therapy at baseline presenting high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs. Outcomes (disease activity, function, and mobility) and body composition parameters were assessed at baseline and every 6 months thereafter. Body composition was assessed by BIA. The association between body composition parameters and outcomes over 1 year was analyzed using longitudinal generalized estimating equations. RESULTS: Seventy-four patients with radiographic axSpA were included in current analysis with a mean age of 36.5 years, disease duration of 6.2 years and ASDAS-CRP score of 3.4 at baseline. Fat mass value and fat mass index were positively associated with disease activity (ASDAS: ß = 0.01, 95% CI [-0.01, 0.03] and ß = 0.04, 95% CI [-0.01, 0.08], respectively) and functional disability (BASFI). Visceral adipose tissue (VAT) was associated with reduced spine mobility (BASMI: ß = 0.20, 95% CI [0.07, 0.33]). Additionally, increase in VAT and fat mass parameters was linked to worse disease activity and functional disability in women, while they were strongly associated with reduced spinal mobility in men. CONCLUSIONS: Higher levels of body fat and VAT were positively associated with increased disease activity, functional disability, and reduced spinal mobility in patients with radiographic axSpA treated with bDMARDs.

Analysis of survival rate and persistence predictors of baricitinib in real-world data from a large cohort of rheumatoid arthritis patients.

Objectives: The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate. Methods: This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan-Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence. Results: Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07-1.49, p = 0.006. Conclusion: Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.

Prediction of ineffectiveness of biological drugs using machine learning and explainable AI methods: data from the Austrian Biological Registry BioReg.

OBJECTIVES: Machine learning models can support an individualized approach in the choice of bDMARDs. We developed prediction models for 5 different bDMARDs using machine learning methods based on patient data derived from the Austrian Biologics Registry (BioReg). METHODS: Data from 1397 patients and 19 variables with at least 100 treat-to-target (t2t) courses per drug were derived from the BioReg biologics registry. Different machine learning algorithms were trained to predict the risk of ineffectiveness for each bDMARD within the first 26 weeks. Cross-validation and hyperparameter optimization were applied to generate the best models. Model quality was assessed by area under the receiver operating characteristic (AUROC). Using explainable AI (XAI), risk-reducing and risk-increasing factors were extracted. RESULTS: The best models per drug achieved an AUROC score of the following: abatacept, 0.66 (95% CI, 0.54-0.78); adalimumab, 0.70 (95% CI, 0.68-0.74); certolizumab, 0.84 (95% CI, 0.79-0.89); etanercept, 0.68 (95% CI, 0.55-0.87); tocilizumab, 0.72 (95% CI, 0.69-0.77). The most risk-increasing variables were visual analytic scores (VAS) for abatacept and etanercept and co-therapy with glucocorticoids for adalimumab. Dosage was the most important variable for certolizumab and associated with a lower risk of non-response. Some variables, such as gender and rheumatoid factor (RF), showed opposite impacts depending on the bDMARD. CONCLUSION: Ineffectiveness of biological drugs could be predicted with promising accuracy. Interestingly, individual parameters were found to be associated with drug responses in different directions, indicating highly complex interactions. Machine learning can be of help in the decision-process by disentangling these relations.

Effectiveness of sequential lines of biologic and targeted small-molecule drugs in psoriatic arthritis: a systematic review.

OBJECTIVE: To assess current evidence for effectiveness of sequential lines of biologic and targeted small-molecule disease-modifying anti-rheumatic drugs (b/tsDMARDs) when used beyond first-line for psoriatic arthritis (PsA). METHODS: A systematic search of the literature (Medline, Embase, bibliographic searches) was undertaken (October and December 2022) to find studies meeting the criteria of assessing effectiveness of b/tsDMARDs beyond first-line in adults with PsA (PROSPERO CRD42022365298). Risk of bias assessment was undertaken (ROBINS-I/Cochrane RoB2). RESULTS: Of 2666 abstracts identified and following a full text review of 177 psoriatic disease studies, 12 manuscripts and two abstracts were eligible. Of the 12 manuscripts, 11 were observational and one was a sub-analysis of a RCT (n = 16 081: average age 49.5 years, female 53.3%). Two abstracts (n = 7186) were included. All studies comparing first- and second-line (three studies) found a reduced response in second-line. On average, DAPSA remission (most reported outcome, eight studies) was achieved in 26%, 19% and 10% first-, second- and third-line TNFi, and 22%, 13% and 11% first-, second- and third-line other bDMARDs, respectively. Responses varied to third-line bDMARDs; four studies found comparable second- and third-line responses, five studies found diminishing responses in sequential lines. CONCLUSION: Predominantly observational studies, inherently at high risk of bias, indicate bDMARDs can be effective to third-line in PsA, but that response is reduced after first line. There is very limited data for more advanced lines of b/tsDMARD. Prospective studies are required to better understand clinical response to advanced lines of treatment in PsA.

The efficacy of tofacitinib combined with bDMARDs in the treatment of ankylosing spondylitis patients with inadequate response to bDMARDs: a retrospective study.

INTRODUCTION: Ankylosing spondylitis(AS) is a chronic inflammatory rheumatic disease primarily affecting the spine and sacroiliac joints. While biologic disease-modifying antirheumatic drugs(bDMARDs) and targeted synthetic DMARDs(tsDMARDs) are popular treatments for AS, there is limited research on their combined use. This study examined a cohort of AS patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib in conjunction with bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach. METHODS: In this study, we retrospectively collected the electronic medical records (EMR) of 15 adult patients with AS who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between January 2018 and June 2022. All patients had received at least one bDMARD treatment for more than three months and still exhibited moderate to high disease activity. Tofacitinib 5 mg bid was added to their original biological treatment. Treatment was continued for a minimum of 12 weeks following the initiation of combination therapy. Changes in ASDAS-CRP and BASDAI scores at week 12 were collected and analyzed from baseline, while changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, and 12 were also collected and analyzed. RESULTS: After 12 weeks of treatment, the overall ASDAS-CRP score decreased significantly from a baseline of 3.82 ± 1.47 (2.83 ~ 4.99) to 1.47 ± 0.48 (0.75 ~ 2.44), with remission achieved by 7 patients (46.7%) and low disease activity achieved by 5 patients (33.3%). The overall BASDAI score also showed significant improvement, decreasing from a baseline of 5.11 ± 1.42 (3.25 ~ 7 0.75) to 1.28 ± 0.70(0.20 ~ 2.55). Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation. CONCLUSION: To a certain extent, our findings provide some evidence supporting the efficacy and safety of the combination of bDMARD and JAK inhibitor tofacitinib in AS patients with inadequate response to bDMARD monotherapy. It effectively controls disease activity while maintaining a relatively low and manageable incidence of adverse events. Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence-based medical support.

Bimekizumab for the treatment of psoriatic arthritis.

INTRODUCTION: Interleukin (IL)-17A and IL-17F have overlapping roles in pro-inflammatory signaling and have been implicated in the pathogenesis of psoriatic disease. Bimekizumab is the first human monoclonal antibody to selectively inhibit IL-17F in addition to IL-17A. Bimekizumab has been studied in several phase II/III trials and has been approved for the treatment of patients with psoriatic arthritis (PsA) in the EU and UK. AREAS COVERED: A literature search identified clinical trials examining the efficacy and safety of bimekizumab for PsA, which were critically appraised. EXPERT OPINION: Clinical trials of bimekizumab in PsA have demonstrated rapid and sustained treatment responses and depth of response across the multiple disease domains. High levels of efficacy were sustained to 152 weeks in phase IIb trials, and to 52 weeks in phase III trials. Bimekizumab was generally well tolerated. As expected, due to the role of IL-17 in the immune response to fungal pathogens, there was an increase in mild-to-moderate, localized fungal infections with bimekizumab treatment, very few of which led to discontinuation. Studies over longer time periods, with relevant comparators from the IL-17A inhibitor class, and real-world data will be important to further define the role of bimekizumab among currently available treatments for PsA. [Figure: see text].

Characteristics of difficult-to-treat axial spondyloarthritis: Results of a real-world multicentric study.

OBJECTIVE: The EULAR task force recently published the difficult-to-treat RA (D2T RA) definition, however, a definition of D2T axSpA is still lacking and limitations in this definition exist. The objectives were to study the characteristics of D2T axSpA patients using the EULAR definition and to study a subgroup of patients with a predefined more stringent definition including a temporal criterion. METHODS: A multicentric retrospective study was performed. D2T axSpA was defined as failure of≥2 b/tsDMARDs with different mechanism of action. Very D2T axSpA was defined as failure of≥2 b/tsDMARDs in less than 2 years of follow-up. D2T and Very D2T axSpA patients were compared to non-D2T (nD2T) axSpA patients. RESULTS: Three hundred and eleven axSpA patients were included: 88 D2T axSpA (28.3%) and 223 non-D2T (nD2T) axSpA (71.7%). Peripheral involvement was more prevalent in the D2T group (34.9 vs. 21.4%; P=0.015). BASDAI level at baseline was higher in the D2T group (63.7±16.5 vs. 58.8±14.7; P=0.015). Fibromyalgia was found to be more frequent in the D2T group vs nD2T group (P<0.001). Twelve patients (3.8%) were categorized as very D2T axSpA. Compared to nD2T, Very D2T patients had a higher CRP level at baseline (42.0±31.3 vs. 17.8±23.1; P=0.010). IBD prevalence at baseline was higher in the very D2T group (41.7 vs. 3.1%; P<0.001). None of the very D2T patients presented a fibromyalgia. CONCLUSION: D2T axSpA was associated with higher disease activity, peripheral involvement, extra-musculoskeletal manifestations and fibromyalgia. Very D2T patients represented a minim proportion of patients after applying a more stringent definition including a temporal criterion of 2 years and might be independent from fibromyalgia.

Cancer risk with biologic and targeted synthetic DMARDs in patients with rheumatic diseases and previous malignancies: Results from the BIOBADASER register.

OBJECTIVE: to investigate the occurrence and relative risk of incident malignancy in patients with rheumatic diseases and previous malignancies treated with biologic and targeted synthetic DMARDs (b/tsDMARDs). METHODS: Cohort study of patients included in BIOBADASER 3.0 up to 2021, treated with b/tsDMARDs and history of a previous malignancy. Incident cancer was defined as any cancer (new primary, local recurrence or metastases) during the drug exposure. Incidence rate ratios of cancer per 1,000 patients-year (PY) and 95 % confidence interval (CI) were estimated. Rates of incident cancer in tsDMARDs and other bDMARDs versus TNFi were compared. RESULTS: A total of 352 patients from over 9,129 patients recorded in BIOBADASER 3.0 had a history of a previous malignancy. Overall, there were 47 incident malignancies (28 solid cancers, 18 non-melanoma skin cancers and 1 melanoma). The overall rate of incident malignancy was 47.4 (95 % CI 35.6-63.1) events/1,000 PY, ranging between 24.5 events/1000 PY in the anti-CD20 group to 93 events/1000 PY in the anti-CTLA-4 group. We did not find differences in the adjusted rate of incident cancer in patients exposed to JAKi [0.5 (95 % CI 0.2-1.7)], anti-CD20 [0.4(95 % CI 0.1-1)], or anti-IL6 [1.1(95 % CI 0.5-2.4)], anti-CTLA-4 [1.5 (95 % CI 0.7-3.1) or anti-IL17 [0.7 (95 % CI 0.2-2.4) versus TNFi therapy. CONCLUSIONS: We did not find differences in the risk of incident cancer in patients with rheumatic diseases and a previous malignancy between TNFi and other b/tsDMARDs. While incident cancers in our cohort were limited, our data is reassuring, awaiting validation in future studies.

Current Status of Biological Treatment in Ankylosing Spondylitis Patients and Some Related Factors.

Background: Axial spondyloarthritis (axSpA) is a potentially disabling inflammatory arthritis of the spine, usually presenting as chronic back pain typically before the age of 45 years. It is often associated with one or more articular features, including synovitis, enthesitis, and dactylitis. It may also be associated with several non-articular features; these include uveitis, psoriasis, and inflammatory bowel diseases1. Objective: The aim of this article is to describe the status of using biological drugs and some related factors in treating ankylosing spondylitis in Vietnam. Methods: A joint prospective and retrospective cross-sectional descriptive study was conducted on 161 ankylosing spondylitis patients treated with biological drugs at the Centre for Rheumatology between January 2018 and July 2021. Data were collected at the first dose and after 3, 6, 12, 24, and 36 months, including general characteristics, clinical and para-clinical features, drug use status, and related factors. Results: Of the 161 patients, 86.3% were male, with a mean age of 31.1 ± 11.6 years and a mean disease duration of 7.6 ± 6.6 years. Most patients were started on biologics at stage II (46.6%) or III (28.6%). Moreover, 68.9% had active disease based on the Bath Ankylosing Spondylitis Disease Activity Index. The most commonly prescribed first-line therapy was anti-tumor necrosis factor (69.6%), with infliximab the most frequently prescribed drug (44.7%). The rate of biological drug treatment decreased gradually from 100% at the start to 77% after one year and 39.1% after three years. Moreover, 74% of patients changed drugs due to non-response, and 50% discontinued treatment for economic reasons. Age was associated with treatment adherence, and drug change rates were higher in female patients and patients with active disease. Age was significantly associated with drug discontinuation (p < 0.05). Conclusion: Infliximab was the most commonly prescribed first-line drug. The rate of biological therapy gradually decreased after three years. Most patients changed drugs due to non-response, and many discontinued the drugs for economic reasons. Among the individual and clinical factors, age was associated with treatment adherence.

Characteristics Of Difficult-To-Treat Psoriatic Arthritis: A Comparative Analysis.

OBJECTIVE: The EULAR task force recently published the difficult-to-treat rheumatoid arthritis (D2T RA) criteria, however, a definition of D2T patients in psoriatic arthritis (PsA) is still lacking. To date, we have little data concerning D2T PsA, especially in real-world. One of the limitations of the D2T RA EULAR definition is the absence of a temporal criterion. The primary endpoint of this work was to study the characteristics of D2T PsA patients using the EULAR definition. The second objective was to study a sub-group of patients with a predefined more stringent definition including a temporal criterion. METHODS: A retrospective study was performed in a tertiary center. D2T PsA was defined as failure of ≥ 2 b/tsDMARDs with different mechanism of action. Very D2T PsA was defined as failure of ≥ 2 b/tsDMARDs in less than 2 years of follow-up. D2T and Very D2T PsA patients were compared to nD2T PsA patients using statistical tests. RESULTS: 150 PsA patients were included (from 2004 to 2015): 49 D2T PsA and 101 nD2T PsA. D2T PsA was associated with a higher prevalence of axial involvement (p=0.030), axial and/or peripheral structural damage (p=0.007) at baseline and more bDMARDs discontinuation due to poor dermatological control (p=0.005). There was no significant difference regarding comorbidities such as obesity, smoking status, fibromyalgia or depression. In multivariate analysis, peripheral structural damage at baseline was found to be a predictive factor for D2T PsA with an OR of 2.57 (1.16 to 5.69; p=0.020). 17 PsA (11.3%) patients were categorized as Very D2T PsA. When compared to nD2T group, proportion of obesity was higher (p=0.015) and axial involvement was more prevalent in the Very D2T group (p=0.020). CONCLUSION: D2T PsA patients had a higher prevalence of axial involvement, peripheral structural damage and therapeutic discontinuation due to poor dermatological control whereas Very D2T PsA patients were more likely obese with axial involvement. Very D2T PsA represent a minim proportion among patients when applying a more stringent definition. Pending the PsA D2T definition by the European and American societies, this study highlights some characteristics that may help practitioners better identify D2T patients.

Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts.

OBJECTIVE: A lack of representation in pivotal trials currently limits guidance for the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in psoriatic arthritis (PsA) patients with a low number of actively inflamed joints. The aim of this study was to compare the effectiveness of a first bDMARD in PsA patients with low vs high number of affected joints. METHODS: PsA patients with available 66/68 joint count assessments were divided into low joint count (LJC) patients when presenting with <3 tender or < 3 swollen joints or high joint count patients (HJC) with > =3 joints in both categories. We studied drug retention as a joint count independent effectiveness variable in LJC and HJC patients in univariate and multivariable adjusted Cox regression models. RESULTS: 197 LJC patients differed not only in joint counts, but also had lower enthesitis scores, less often dactylitis, less disability and a better health related quality of life at first bDMARD initiation than 190 HJC patients. However, LJC were less often on conventional synthetic (cs) DMARDs. Despite these differences at baseline, bDMARD retention was not significantly different between LJC and HJC in both crude and adjusted analyses (Hazard Ratio (HR) 1.09 [0.76-1.58], p= 0.52). Furthermore, bDMARD retention was significantly better (HR 0.63 [0.47-0.85], p< 0.002) when administered with csDMARD co-therapy. CONCLUSIONS: Biological DMARDs were similarly effective in terms of drug retention in patients with low and high joint counts. In the setting of absent remission and a significant disease burden, bDMARDs should not be withheld from patients because they exhibit only a low joint count.

Comparative effectiveness of treatments for rheumatoid arthritis in clinical practice: A systematic review.

OBJECTIVE: To assess real-world comparative effectiveness studies of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA) through a systematic review. METHODS: We searched Medline for journal articles (2001-2021) and Embase® for abstracts presented at the European Alliance of Associations for Rheumatology and American College of Rheumatology (ACR) 2020 and 2021 annual meetings on non-randomized studies comparing the effectiveness of b/tsDMARDs using ACR-recommended disease activity measures, measures of functional status, and patient-reported outcomes (HAQ, PROMIS PF, patient pain, Patient and Physician Global Assessment of disease activity). Methodological heterogeneity between studies precluded meta-analyses. Risk of bias was assessed using the Cochrane Risk Of Bias In Non-randomized Studies of Interventions-I tool. RESULTS: Of 1283 records screened, 68 were selected for data extraction, of which 1 was excluded due to critical risk of bias. Most studies were multicenter observational cohort/registry studies (n = 60) and were published between 2011 and 2021 (n = 60). Mean or median reported RA duration was between 6 and 15 years. Disease Activity Score in 28 joints (46 studies), Clinical Disease Activity Index (37 studies), and Health Assessment Questionnaire-Disability Index (32 studies) were the most common outcomes used in clinical practice, with regional differences identified. The most common comparison was between tumor necrosis factor inhibitors (TNFis) and non-TNFi bDMARDs (35 studies). There were no evident differences between b/tsDMARDs in clinical effectiveness. CONCLUSION: This systematic review summarizing real-world evidence from a very large number of global studies found there are many effective options for the treatment of RA, but relatively less evidence to support the use of any one b/tsDMARD or drug class over another. Treatment for patients with RA should be tailored to suit individual clinical profiles. Further research is needed to identify whether specific patient subgroups may benefit from specific drug classes.

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis.

BACKGROUND: Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. METHODS: We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. RESULTS: The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. CONCLUSION: We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

Subcutaneous abatacept for the treatment of rheumatoid arthritis in routine clinical practice in Germany, Austria, and Switzerland: 2-year retention and efficacy by treatment line and serostatus.

INTRODUCTION/OBJECTIVES: The ASCORE study on treatment for rheumatoid arthritis (RA) showed better retention and clinical response rates for abatacept as first-line versus later-line therapy. This post hoc analysis of ASCORE assessed 2-year retention, efficacy, and safety of subcutaneous (SC) abatacept in Germany, Austria, and Switzerland. METHODS: Adults with RA who initiated SC abatacept 125 mg once weekly were assessed. Primary endpoint was abatacept retention rate at 2 years. Secondary endpoints: proportions of patients with low disease activity (LDA)/remission per Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (≤ 3.2), Simplified Disease Activity Index (≤ 11), and Clinical Disease Activity Index (≤ 10). Outcomes were analyzed by treatment line and serostatus. RESULTS: For the pooled cohort, the 2-year abatacept retention rate was 47.6%; retention was highest in biologic-naïve patients (50.5% [95% confidence interval 44.9, 55.9]). Patients seropositive for both anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF; + / +) at baseline had a higher 2-year abatacept retention rate than patients with single seropositivity for either APCA or RF or double-seronegativity (- / -), irrespective of treatment line. At 2 years, a higher proportion of patients who were biologic-naïve were in LDA/remission than patients with one or ≥ two prior biologics. CONCLUSION: A higher proportion of patients with + / + RA (compared with - / - RA) had abatacept retention after 2 years. Early identification of patients with seropositive RA may facilitate a precision-medicine approach to RA treatment, leading to a higher proportion of patients in LDA/remission. TRIAL REGISTRATION NUMBER: NCT02090556; date registered: March 18, 2014 (retrospectively registered). Key Points • This post hoc analysis of a German-speaking subset of European patients with RA from the global ASCORE study (NCT02090556) showed that retention of SC abatacept within this subset was 47.6%, with good clinical outcomes after 2 years. • Patients with double-seropositive RA (ACPA and RF positive) had higher retention of abatacept than patients with double-seronegative RA (ACPA and RF negative). Retention and clinical responses were highest for patients who were biologic-naïve compared with patients who had one or ≥ two prior biologic treatments. • These real-world data may be useful for clinicians in informing individualized treatment pathways for patients with RA, and fostering superior disease control and clinical outcomes.

The accelerated waning of immunity and reduced effect of booster in patients treated with bDMARD and tsDMARD after SARS-CoV-2 mRNA vaccination.

Objectives: This study aimed to assess the duration of humoral responses after two doses of SARS-CoV-2 mRNA vaccines in patients with inflammatory joint diseases and IBD and booster vaccination compared with healthy controls. It also aimed to analyze factors influencing the quantity and quality of the immune response. Methods: We enrolled 41 patients with rheumatoid arthritis (RA), 35 with seronegative spondyloarthritis (SpA), and 41 suffering from inflammatory bowel disease (IBD), excluding those receiving B-cell-depleting therapies. We assessed total anti-SARS-CoV-2 spike antibodies (Abs) and neutralizing Ab titers 6 months after two and then after three doses of mRNA vaccines compared with healthy controls. We analyzed the influence of therapies on the humoral response. Results: Patients receiving biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) showed reduced anti-SARS-CoV-2 S Abs and neutralizing Ab titers compared with HC or patients receiving conventional synthetic (cs)DMARDs 6 months after the first two vaccination doses. Anti-SARS-CoV-2 S titers of patients with b/tsDMARDs declined more rapidly, leading to a significant reduction in the duration of vaccination-induced immunity after two doses of SARS-CoV-2 mRNA vaccines. While 23% of HC and 19% of patients receiving csDMARDs were without detectable neutralizing Abs 6 months after the first two vaccination doses, this number was 62% in patients receiving b/tsDMARDs and 52% in patients receiving a combination of csDMARDs and b/tsDMARDs. Booster vaccination led to increased anti-SARS-CoV-2 S Abs in all HC and patients. However, anti-SARS-CoV-2 S Abs after booster vaccination was diminished in patients receiving b/tsDMARDs, either alone or in combination with csDMARDs compared to HC. Conclusion: Patients receiving b/tsDMARDs have significantly reduced Abs and neutralizing Ab titers 6 months after mRNA vaccination against SARS-CoV-2. This was due to a faster decline in Ab levels, indicating a significantly reduced duration of vaccination-induced immunity compared with HC or patients receiving csDMARDs. In addition, they display a reduced response to a booster vaccination, warranting earlier booster vaccination strategies in patients under b/tsDMARD therapy, according to their specific Ab levels.

Gender-specific differences in patients with psoriatic arthritis receiving ustekinumab or tumour necrosis factor inhibitor: real-world data.

OBJECTIVE: Investigate effects of gender on disease characteristics and treatment impact in patients with PsA. METHODS: PsABio is a non-interventional European study in patients with PsA starting a biological DMARD [bDMARD; ustekinumab or TNF inhibitor (TNFi)]. This post-hoc analysis compared persistence, disease activity, patient-reported outcomes and safety between male and female patients at baseline and 6 and 12 months of treatment. RESULTS: At baseline, disease duration was 6.7 and 6.9 years for 512 females and 417 males respectively. Mean (95% CI) scores for females vs males were: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), 32.3 (30.3, 34.2) vs 26.8 (24.8, 28.9); HAQ-Disability Index (HAQ-DI), 1.3 (1.2, 1.4) vs 0.93 (0.86, 0.99); total PsA Impact of Disease-12 (PsAID-12) score, 6.0 (5.8, 6.2) vs 5.1 (4.9, 5.3), respectively. Improvements in scores were smaller in female than male patients. At 12 months, 175/303 (57.8%) female and 212/264 (80.3%) male patients achieved cDAPSA low disease activity, 96/285 (33.7%) and 137/247 (55.5%), achieved minimal disease activity (MDA), respectively. HAQ-DI scores were 0.85 (0.77, 0.92) vs 0.50 (0.43, 0.56), PsAID-12 scores 3.5 (3.3, 3.8) vs 2.4 (2.2, 2.6), respectively. Treatment persistence was lower in females than males (P ≤ 0.001). Lack of effectiveness was the predominant reason to stop, irrespective of gender and bDMARD. CONCLUSIONS: Before starting bDMARDs, females had more severe disease than males and a lower percentage reached favourable disease states, with lower persistence of treatment after 12 months. A better understanding of the mechanisms underlying these differences may improve therapeutic management in females with PsA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02627768.

Effect of Anti-TNF Treatment on Mooren's Ulcer: A Case Series and Review of the Literature.

PURPOSE: To report the efficacy of systemic anti-TNF agents in Mooren's ulcer. DESIGN: Retrospective, consecutive case series. METHODS: We report on clinical characteristics and outcome of five patients with Mooren's ulcer with anti-TNF treatment. RESULTS: During a mean follow-up of 30 months, relief of symptoms and arrest of corneal melting were observed in all eyes. Systemic corticosteroid treatment could be discontinued or reduced to threshold levels. No patient experienced adverse effects on bDMARDs. CONCLUSIONS: Our results suggest that bDMARDs are effective in Mooren's ulcer unresponsive to conventional treatment. This is in line with accumulating evidence in the current literature. Therefore, more targeted immunomodulatory approaches might be an effective first-line therapy in the future.