Antirheumatic Research Articles

Comparative Effectiveness of Bimekizumab and Risankizumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

The relative efficacy of bimekizumab and risankizumab in patients with PsA who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR) was assessed at 52weeks (Wk52) using matching-adjusted indirect comparisons (MAIC). Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons. In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95% confidence interval]: 1.52 [1.11, 2.09]) and ACR70 (1.80 [1.29, 2.51]). In patients who were TNFi-IR, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR20 (1.78 [1.08, 2.96]), ACR50 (3.05 [1.74, 5.32]), ACR70 (3.69 [1.82, 7.46]), and MDA (2.43 [1.37, 4.32]). Using MAIC, bimekizumab demonstrated a greater likelihood of efficacy in most ACR and MDA outcomes than risankizumab in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52. NCT03895203, NCT03896581, NCT03675308, NCT03671148.

Comparative Effectiveness of Bimekizumab and Ustekinumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

A matching-adjusted indirect comparison (MAIC) was conducted to assess the relative efficacy at 52weeks (Wk52) of bimekizumab 160mg every 4weeks (Q4W) and ustekinumab 45 or 90mg every 12weeks (Q12W) in patients with psoriatic arthritis (PsA) who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or who had a previous inadequate response or an intolerance to tumor necrosis factor inhibitors (TNFi-IR). Relevant trials were systematically identified. Individual patient data from the bimekizumab trials BE OPTIMAL (NCT03895203; N = 431) and BE COMPLETE (NCT03896581; N = 267) were matched with summary data on patients receiving ustekinumab in the PSUMMIT 1 trial (NCT01009086; 45mg, N = 205; 90mg; N = 204) and a subgroup of TNFi-IR patients receiving ustekinumab in the PSUMMIT 2 trial (NCT01077362; 45mg, N = 60; 90mg, N = 58), respectively. Patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of the ustekinumab trial patients. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Non-placebo-adjusted comparisons of recalculated bimekizumab and ustekinumab outcomes for the American College of Rheumatology (ACR) 20/50/70 response criteria (non-responder imputation) were analyzed. In patients who were bDMARD naïve, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (odds ratio [95% confidence interval] 45mg: 2.14 [1.35, 3.40]; 90mg: 1.98 [1.24, 3.16]), ACR50 (45mg: 2.74 [1.75, 4.29]; 90mg: 2.29 [1.48, 3.55]), and ACR70 (45mg: 3.33 [2.04, 5.46]; 90mg: 3.05 [1.89, 4.91]). In patients who were TNFi-IR, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (45mg: 4.17 [2.13, 8.16]; 90mg: 4.19 [2.07, 8.49]), ACR50 (45mg: 5.00 [2.26, 11.05]; 90mg: 3.86 [1.70, 8.79]), and ACR70 (45mg: 9.85 [2.79, 34.79]; 90mg: 6.29 [1.98, 20.04]). Using MAIC, bimekizumab showed greater efficacy than ustekinumab in achieving all ACR responses in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52. NCT03895203, NCT03896581, NCT01009086, NCT01077362.

Management of Rheumatoid Arthritis By Development of Nanocarriers and their Significance Over Conventional Dosage Forms

Background: Rheumatoid Arthritis is one of the most common auto-immune diseases that cause inflammation. It is characterized by pain, stiffness, tenderness, and swelling in joints, which may even lead to heart, lungs, or brain-related problems where age is the major factor involved, as around 55% older adults have been affected by it. Treatments including non-steroidal anti- inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) etc., that are modified and formulated as nanocarriers for enhanced bioavailability, majorly aim at enhancing the rate and extent of drug reaching the bloodstream such as solid-lipid nanoparticles, liposomes, polymeric- micelles, polymeric nanoparticles etc. are used in the management of rheumatoid arthritis. Methods: The following tools (Pubmed, Scopus, Google search engine, Google Scholar, Medline Search Engine, Elsevier) were used in the literature search. Results: Through the literature review, the development of nanocarrier shows a promising approach in the management of rheumatoid arthritis as compared to the conventional drug treatment such as biologic agents and non-steroidal anti-inflammatory drugs etc. Conclusion: Rheumatoid Arthritis is a condition that occurs when the immune system, which normally helps to protect the body from infection and disease, attacks its own tissues. The disease causes pain, swelling as well as loss of function in joints. Therefore, life-long management is required by reducing the dose frequency and dosage regimen, which can be effectively approached by the development of a nano-carrier for significant drug uptake and low toxicity.

Potential difficult-to-treat psoriatic arthritis real-world prevalence and contributing factors.

The challenge of achieving low disease activity or remission in psoriatic arthritis (PsA) is an unmet need for many patients. Persistent disease activity in PsA may require treatment adjustments due to its complex pathogenesis and varied tissue involvement, highlighting the need for dedicated definitions. This study evaluates patients' frequency and contributing factors with potential "difficult-to-treat PsA (D2TPsA)", similar to the EULAR definition of D2T rheumatoid arthritis. A retrospective study was conducted at two tertiary centres to define potential D2TPsA, defined as failure of ≥1 conventional synthetic disease-modifying anti-rheumatic drug (DMARD) and ≥2 biological or targeted synthetic DMARDs with different mechanisms of action. Of the 171 patients included in the study, 116 (67.8%) were women; the average age was 48.16 ±11.23 years. D2TPsA was detected in 33 patients (19.3%). This group exhibited a longer disease duration, higher disease burden (median number of tender and swollen joints, patient and physician global evaluation, morning stiffness, erythrocyte sedimentation rate and C-reactive protein, DAPSA), HLA-B27 positivity, and higher prevalence of peripheral involvement. Secukinumab usage and mean glucocorticosteroid dosage were significantly higher in the D2TPsA group. Comorbidities such as fibromyalgia (FM) and diabetes mellitus (DM) and the median number of comorbidities were significantly higher in D2TPsA. In multivariate analysis, FM, DM, and HLA-B27 positivity were independently associated with D2TPsA. This study underscores the impact of comorbidities on PsA disease activity and emphasises the need for further research to differentiate treatment challenges influenced by comorbidities from true treatment resistance.

Survival in patients with rheumatoid arthritis and early breast cancer treated with tumor necrosis factor inhibitors.

There have been concerns about the use of tumor necrosis factor inhibitors (TNFi) for autoimmune disease in patients with recently diagnosed cancer. We assessed the survival of patients with rheumatoid arthritis (RA) and newly diagnosed early breast cancer (BC) treated with TNFi in the first two years after BC diagnosis. We identified patients in two datasets: (1) Optum's de-identified Clinformatics® Data Mart Database (CDM), (2) Surveillance, Epidemiology, and End Results program (SEER) and Texas Cancer Registry (TCR) Medicare-linked cohort. We grouped patients according to whether they received TNFi, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) only, or no DMARDs within 2years after BC. Outcomes were overall survival (OS) and BC-specific survival (BCSS). We conducted landmark analyses at years 1 and 2, with multivariable Cox regressions using propensity scores for adjustment. In the first year after BC, 165/970 (17.0%) and 201/1246 (16.1%) patients received TNFi in CDM and SEER/TCR-Medicare respectively. In the 1year landmark, no significant differences in OS were observed between patients treated with TNFi and patients treated with csDMARDs only in CDM (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.42-1.40) or SEER/TCR-Medicare (HR = 0.84, 95% CI 0.54-1.31). BCSS (SEER/TCR-Medicare) was better in patients receiving TNFi than in those receiving csDMARDs only (HR = 0.28, 95% CI 0.08-0.98). In CDM, glucocorticoid therapy had worse OS than those without glucocorticoids (HR = 2.18, 95% CI 1.13-4.18). This was also observed in SEER/TCR-Medicare (not statistically significant). Similar results were observed for the 2year landmark. TNFi treatment during the first two years after early BC was not associated with worse survival.

Impact of blue-collar vs. white-collar occupations on disease burden in psoriatic arthritis patients: A Swiss clinical quality management in rheumatic diseases cohort study

Biomechanical stress may exacerbate inflammation in psoriatic arthritis (PsA). This study aimed to investigate disease activity, work disability, and drug response/retention rates in PsA patients among two different occupation’s types: blue-collar workers (BCol) with manual labor versus white-collar workers (WCol) with sedentary occupations. PsA patients registered in the Swiss cohort (SCQM) were classified as BCol or WCol workers and assessed at the initiation of a biologic or targeted synthetic disease-modifying anti-rheumatic drug (b-/tsDMARD). We compared the baseline characteristics at treatment start and the DAS28-CRP for the 1-year remission. Treatment retention was investigated using Kaplan–Meier curves and Cox regression analysis. Multivariable models were adjusted for potential confounders. Of 564 patients, 29% were BCol, and 71% were WCol workers. Baseline disease activity was comparable between both groups. BCol workers were predominantly male (79.8%) and more work disabled at baseline (84.0% vs. 27.9%; p < 0.01). One hundred seventy-four treatment courses (TCs) of 165 PsA patients were included for longitudinal analysis. Occupation did not significantly influence the achievement of DAS28-CRP remission at 1 year. Kaplan–Meier analysis (n = 671) indicated longer retention for BCol workers (mean retention duration: 3.15 years vs. 2.15 years, (p = 0.006). However, adjusted Cox regression analysis did not corroborate these findings. This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients, while treatment response seems to be unaffected by the patients’ occupation type. Additional research is required to thoroughly comprehend the relationship between physical workload, disease activity, and treatment outcomes.Key Points• This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients.• The treatment response among of PsA patients seems unaffected by the patients’ occupation type.

Effectiveness of methotrexate and bridging glucocorticoids with or without early introduction of a 6-month course of etanercept in early RA: results of the 2-year, pragmatic, randomised CareRA2020 trial

ObjectivesTo investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction...

Reactivation of Hepatitis B Virus among Malignancy Patients Undergoing Chemotherapy: A Prospective Cohort Study

Abstract Introduction: Reactivation of hepatitis B virus (HBV) can occur in patients receiving short-term chemotherapy, long-term immunosuppressive therapy, or disease-modifying antirheumatic agents for rheumatological diseases and is more common in hepatitis B surface antigen-positive patients. However, there is a lack of data for reactivation among malignant patients undergoing chemotherapy in resolved HBV patients. Methodology: A prospective cohort study of 200 oncological patients on chemotherapy was conducted for the reactivation of the HBV for a year. Patients underwent a thorough physical examination; baseline assessment and biochemical test and test were repeated at each follow-up. Results: The majority were females and in the 40–60-year age group. Age and serum albumin levels were significantly different (P &lt; 0.05) among the reactivated versus the nonreactivated groups. Hepatitis B reactivation was seen in 14 (7%) patients with a maximum in the rituximab therapy group (11.26%). There was no statistically significant difference in baseline ALT levels between patients who experienced reactivation and those who did not. Conclusion: In the present study population, 7% had hepatitis B reactivation. The present study identifies old age, low serum albumin, and rituximab chemotherapy as significant risk factors for reactivation. Prophylactic antiviral therapy seems to be effective as no reactivation has occurred in this group.

Real-World Drug Survival of Biologics and Targeted Synthetic Disease-Modifying Anti-rheumatic Drugs Among Patients with Psoriatic Arthritis.

While the variety of biologics (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) available for patients with psoriatic arthritis (PsA) has proved to be efficacious in randomized clinical trials, there is a growing importance to understand the benefits and potential drawbacks of these different therapies in real-world settings, which includes bio-experienced and older patients as well. To evaluate the real-world adherence, drug survival, and discontinuation risk of bDMARDs and tsDMARDs among patients with PsA, comprising both younger and older patients. A retrospective studyusing a computerized database. Treatment-naïve and treatment-experiencedpatients with PsA, younger and older than 60 years, who initiated treatment with bDMARDs [TNF-α inhibitors (TNF-αis), IL-17 inhibitors (IL-17is), IL-12/23 inhibitors (IL-12/23i)] or tsDMARDs (the PDE-4 inhibitor apremilast) during 2015-2018 were included. Adherence was assessed using the proportion of days covered (PDC) method. Time to discontinuation was analyzed using Kaplan-Meier estimates. Risk of discontinuation was estimated by Cox proportional hazard model. We identified 427 eligible patients (22.2 % were older than 60 years), utilizing 673 treatment lines. The proportion of adherent patients (PDC ≥0.8) was similar (62.1-66.5%) across all lines of therapy and across different biologics (70.0-72.0%), while apremilast showed the lowest, in both treatment-naïve and experienced settings (43.6% and 25.5%, respectively). The Kaplan-Meier analysis showed that in the treatment-naïve TNF-αis had higher drug survival compared with apremilast (P = 0.032). Apremilast also had the lowest drug survival in the treatment-experienced group (P < 0.0001). Kaplan-Meier analysis by age groups showed similar drug survival rates in older (≥ 60 years) and younger (age < 60 years) patients, regardless of treatment-experience status. The multivariable model showed that apremilast had increased risk for discontinuation compared with TNF-αis. Adherence, drug survival and risk for discontinuation were similar for all included bDMARDs, regardless of treatment experience status, while apremilast showed lower rates and increased risk. Adherence and discontinuation rate were similar in older and younger patients. With the variety of drug modes of action available for patients with PsA, these findings may assist caregivers in selecting the appropriate treatment.

THE RELATIONSHIP BETWEEN TOCILIZUMAB USE AND EOSINOPHIL COUNT IN PATIENTS WITH RHEUMATOID ARTHRITIS: A RETROSPECTIVE STUDY

Objective: This study aimed to determine the relationship between tosilizumab use and eosinophil counts in patients with rheumatoid arthritis. Material and Methods: Thirty five patients diagnosed with rheumatoid arthritis (RA) receiving either synthetic disease-modifying antirheumatic drugs (DMARDs) or tocilizumab treatment were included in this study. Patient age and disease duration, disease activity parameters and eosinophil values were recorded. Results: Comparing the eosinophil counts and percentages of the DMARD group with the Tocilizumab group, any statistically significant differences were found. There was no significant difference in eosinophil counts and percentages in the DMARD group in repeated measurements. However, in the Tocilizumab group, there was a significant difference in both parameters. Conclusion: A significant increase in eosinophil counts was observed in the group receiving tocilizumab therapy at the 1st month. Therefore, during treatment monitoring, especially in the early stages, attention should also be paid to eosinophil values.

Additional Value of Ultrasound in Patients with Psoriatic Arthritis within Treatment Target.

Background: In psoriatic arthritis (PsA), musculoskeletal ultrasound is a complementary tool to physical examination, useful even in patients in remission to detect subclinical activity. Objectives: The objective of the study was to assess the ultrasound prevalence of active enthesitis and synovitis in patients who reached the therapeutic target. Methods: This cross-sectional study included patients with at least 6 months of therapy with a targeted synthetic or biological disease-modifying antirheumatic drug who were in treatment target (i.e., DAPSA < 14). Patients underwent bilateral clinical and ultrasound examination of the elbow lateral epicondyle, quadriceps insertion, distal patellar tendon insertion, and Achilles enthesis for assessing enthesitis, and hand and foot joints for assessing synovitis. Enthesitis and synovitis were considered active if the power Doppler signal showed at least a score of one. Results: The study included 51 PsA patients, women (52.9%), with an average age of 55 years. Although the patients were within the DAPSA treatment target, 21.6% had at least one painful enthesis at clinical examination, 19.6% had ultrasound evidence of at least one active enthesitis and 15.7% had ultrasound signs of at least one active synovitis. Conclusions: Among PsA patients thought to be within the therapeutic target, ultrasound detected a non-negligible percentage of active enthesitis and synovitis.

Faster steroid-free remission with tocilizumab compared to methotrexate in giant cell arteritis: a real-life experience in two reference centres.

Glucocorticoids (GCs) are still the mainstay of treatment of giant cell arteritis (GCA). Although GCs are highly effective in GCA, the high burden of toxicity of GCs as well as the disease relapse during GC tapering is well documented. To compare the efficacy and rapidity of TCZ and MTX as steroid-sparing agents in a real-life cohort of GCA patients. A retrospective analysis was conducted including patients with newly diagnosed GCA from the Rheumatology Units of Udine and Rome. The inclusion criterion was the treatment with TCZ or MTX as first steroid-sparing drug. 112 GCA patients (81 females) with a median age of 70 (IQ 65-75) years were collected. Thirty-one out of 112 (27.7%) patients were treated with TCZ (162mg/week), while 81/112 (72.3%) patients received MTX (up to 20mg/week) as a GC-sparing agent. At month 6 after GCA onset, 5/31 (16.1%) patients in TCZ group and none in MTX group were in GC-free sustained remission (p value = 0.001). Similarly, at month 12, 64.5% (20/31) and 11.1% (9/81) of patients were in sustained GC-free remission in TCZ and MTX group, respectively (p value <0.001). At month 24 of follow-up, at least one relapse of the disease occurred in 7/31 (22.6%) in TCZ-treated and 28/81 (34.6%) in MTX-treated patients, respectively (p value = 0.22). TCZ allowed a faster discontinuation of steroid therapy than MTX in GCA patients, without increasing the risk of relapse.

Low-Dose Glucocorticoids in Older Patients with Rheumatoid Arthritis: What Does the Evidence Say?

The short-term use of glucocorticoids (GCs) in combination with methotrexate was recommended for the initial treatment of rheumatoid arthritis by the European League Against Rheumatism. A randomized controlled trial (GLORIA) showed that treatment of older patients with low-dose GCs in combination with disease-modifying anti-rheumatic drugs was more efficacious than disease-modifying anti-rheumatic drugs plus placebo in terms of disease activity control and prevention of joint destruction. Glucocorticoid-related adverse events were likely to increase relative to placebo, with no increase in serious adverse events and fractures over 2 years. Observational studies showed an increased risk of serious infections, cardiovascular events, and fractures associated with long-term continuation of GCs in older patients, but the adverse events may be associated not only with GC toxicity but also with poor disease control of rheumatoid arthritis. In the GLORIA study, low-dose GCs during 2 years could be tapered off safely, but many patients had a flare of disease activity after discontinuation of GCs. In the two representative large Japanese registries (IORRA and NinJa), the proportion of patients using GCs and non-tumor necrosis factor inhibitors increased with increasing age at disease onset, with a decreasing trend in methotrexate use. The proportion of patients in remission with GC treatment also increased with increasing age at onset. These suggested that it is not easy to discontinue GCs in older patients. If GCs cannot be terminated in the short term, it may be acceptable to use GCs to control disease activity for up to 2 years.

Association Between Achievement of Clinical Disease Control and Improvement in Patient-Reported Outcomes and Quality of Life in Patients With Psoriatic Arthritis in the Phase 3 SELECT-PsA 1 and 2 Randomized Controlled Trials.

We explored the relationship between achievement of clinical disease control and improvements in and normative values for patient-reported outcomes (PROs), including quality of life (QoL) measures, in patients with psoriatic arthritis (PsA). This was a post hoc analysis of 104-week data from the SELECT-PsA 1 and 2 trials in adults with PsA and inadequate response to one or more conventional synthetic (SELECT-PsA 1) or biologic (SELECT-PsA 2) disease-modifying antirheumatic drug. Patients were initially randomized to upadacitinib 15 mg once daily (QD) to placebo switched to upadacitinib 15 mg QD at week 24 or to adalimumab 40 mg every other week (SELECT-PsA 1 only), and data were pooled across treatments and analyzed. We evaluated several clinical disease control measures (minimal disease activity [MDA]; very low disease activity [VLDA]; and low disease activity [LDA] and/or remission by Disease Activity in Psoriatic Arthritis [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and Routine Assessment of Patient Index Data 3 [RAPID3]) and examined their associations with improvements and normative values for various PROs. A total of 1,069 and 317 patients were analyzed for SELECT-PsA 1 and 2, respectively. In both studies, responders (patients who achieved MDA or VLDA, and DAPSA, PASDAS, and RAPID3 LDA or remission) at week 104 achieved more marked changes from baseline, and more responders achieved normative values in PROs compared with nonresponders (most nominal P < 0.0001). Furthermore, numerically larger proportions of responders achieved minimal clinically important differences across PROs compared with nonresponders in both studies. In addition, patients who achieved MDA or VLDA were more likely to achieve DAPSA, PASDAS, and RAPID3 LDA or remission (all nominal P < 0.0001) for upadacitinib 15 mg QD and when treatment arms were pooled. Patients with PsA who achieve clinical disease control are more likely to achieve improvements and normative values in PROs and QoL measures, which reinforces disease control as a treatment target.

Effects and Safety of 5% Lifitegrast Ophthalmic Solution in Patients With Dry Eye Disease Associated With Ocular Graft-Versus-Host Disease.

Introduction Graft-versus-host disease (GVHD) is a common sequela of hematopoietic stem cell transplant (HSCT). While HSCT is often curative for certain hematologic malignancies, acute and chronic GVHD remains an important cause of morbidity and mortality in post-transplant patients. Ocular involvement is one manifestation of chronic GVHD that can present similarly to chronic dry eye with tear film abnormalities, aqueous deficiency, and corneal epithelial defects through melting and perforation. Current management includes frequent use of artificial tears and oral or topical glucocorticoids as tolerated. There is a need for long-term, steroid-sparing therapeutics in the management of ocular GVHD (oGVHD). Lifitegrast is approved for the treatment of chronic dry eye and may have therapeutic potential in the treatment of oGVHD. The aim of this study was to investigate the efficacy and safety of topical lifitegrast in the management of oGVHD. Methodology A prospective randomized clinical trial (NCT04792580) was performed on 32 enrolled patients with diagnosed oGVHD. Subjects underwent a two-week washout period consisting of preservative-free artificial tears dosed twice a day, after which they were randomized to the treatment arm (5% lifitegrast ophthalmic solution) or placebo arm (vehicle solution) for four weeks. Endpoints included Symptom Assessment iN Dry Eye (SANDE) score, unanesthetized Schirmer score, Ocular Surface Disease Index questionnaire score, fluorescein staining, tear film breakup time, meibum quantity, and turbidity. Safety endpoints included intraocular pressure, visual acuity, and rate of treatment-related adverse effects. Statistical analysis was done with a t-test or Wilcoxon rank-sum test. Results The primary and secondary efficacy endpoints were met, with statistically significant reductions in mean SANDEand unanesthetized Schirmer score observed at four weeks post-randomization. No serious adverse events related to the use of either lifitegrast or vehicle were observed, and no worsening of visual acuity or intraocular pressure occurred in the intention-to-treat analysis. However, further inference was limited due to insufficient statistical power owing to significant washout and a 50% dropout rate from the all-enrolled analysis set. The most common causes of study dropout were worsening of unrelated medical conditions (not GVHD) and improvement of SANDE score or Schirmer score outside of the inclusion criteria range during the washout period. Conclusions Lifitegrast may be a useful steroid-sparing agent in the long-term management of oGVHD. This study provides further support for the clinical evidence of lifitegrast in the management of dry eye signs and symptoms, although further sufficiently powered clinical trials are warranted to better understand its efficacy in the oGVHD population. Personalized treatment options targeting distinct manifestations of oGVHD in the cornea, tear film, lid margin, and conjunctiva are needed in the effective management of this multifaceted and complex disease.

From Psoriasis to Psoriatic Arthritis: Decoding the Impact of Treatment Modalities on the Prevention of Psoriatic Arthritis.

Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis. This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group1, topical therapy; group2, phototherapy; group3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group4, biologic DMARDs which was also stratified according to biologic class. The PsA incidence rate was lower in the biologic agents' group versus the methotrexate group (HR 0.46 [95%CI 0.35-0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95%CI 1.65-2.07]). Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor.

Contemporary Concise Review 2023: Asthma.

Asthma research and management needs to meet the priorities of the end user-patients, carers and clinicians. A better understanding of the natural history of asthma and the progression of disease has highlighted the importance of early identification of patients with asthma and the potential role of early intervention. Management of mild asthma requires a consistent approach with the same detail and consideration used when managing severe disease. Evidence around treatable traits approaches continues to evolve, supporting the role of a personalized medicine in asthma. Oral corticosteroid (OCS) stewardship continues to be an urgent issue in asthma management. Strategies to taper OCS doses and the implementation of biologic therapies for their steroid sparing benefits will be important steps to address this problem. The concept of remission in asthma provides an ambitious target and treatment outcome.

Joint Damage and Low Lean Body Mass in a Cohort of Peruvian Patients With Rheumatoid Arthritis.

To determine the association between radiologic joint damage (JD) and a lower lean body mass (LBM) in rheumatoid arthritis (RA) patients. A cross-sectional study from a single center established RA cohort. JD and appendicular LBM (arms and legs) were measured with the Sharp/van der Heijde (SvdH) score and dual x-ray absorptiometry expressed as kg/m 2 , respectively. A univariable analysis was used to determine the association between JD an LBM; then, a multivariable regression model was performed to evaluate the persistence of this association, adjusted by age, gender, disease duration, socioeconomic status (by the Graffar method), tobacco use, anticitrullinated protein antibody levels, Disease Activity Score in 28 joints for RA with erythrocyte sedimentation rate, glucocorticoid use (as prednisone equivalent), disease-modifying antirheumatic drug use, body mass index, and disability (by the multidimensional Health Assessment Questionnaire). Two hundred forty-seven patients were included; the average (SD) age was 63.0 (12.8) years, disease duration 20 (15.00) years, the total SvdH was 66 (86.75), and the aLBM was 13.6 (3.82) kg/m 2 . In the univariable analysis, a lower appendicular LBM was associated with higher SvdH score on the female population, in terms of the total ( B = -8.6, p < 0.01), bone erosion (-4.4, p < 0.01), and joint space narrowing (-4.2, p < 0.01) scores; this correlation remained in the multivariable analysis in terms of total SvdH ( B = -9.5, p < 0.01), bone erosion (-5.2, p < 0.01), and joint space narrowing (-4.3, p < 0.01). A lower LBM in female patients was associated with more severe JD independently of other variables examined. Strategies aimed at preserving LBM could have a favorable impact on the course of disease.

Association between disease activity of rheumatoid arthritis and risk of complications following total hip arthroplasty: a retrospective cohort study

BackgroundIdentifying rheumatoid arthritis patients at higher risk of complications after total hip arthroplasty could make perioperative management more effective. Here we examined whether disease activity is associated with risk of such complications.MethodsWe retrospectively analyzed data for 337 rheumatoid arthritis patients at our medical center who underwent primary total hip arthroplasty. Rheumatoid arthritis patients were categorized according to the simplified disease activity index (SDAI), the values of which at admission and follow-up were averaged together. Logistic regression was used to examine associations of mean SDAI with rates of dislocation, infection, periprosthetic fracture and aseptic loosening. As controls, 337 osteoarthritis patients who did not have systemic inflammation and who underwent the same procedure were matched across numerous clinicodemographic variables.ResultsAmong the 337 rheumatoid arthritis patients, 38 (11.3%) had postoperative complications, the rates of which varied significantly from 0 to 17.5% (p = 0.003) among the four subgroups whose disease activity based on mean SDAI was categorized as high, moderate, low or in remission. Each 1-unit increase in mean SDAI was associated with a significant increase in risk of postoperative complications (OR 1.015, 95% CI 1.001–1.029, p = 0.035). Across all rheumatoid arthritis patients, rate of complications did not differ significantly between patients who received disease-modifying anti-rheumatic drugs or other treatments. Rates of dislocation, of infection or of all postoperative complications combined were significantly lower among osteoarthritis controls than among rheumatoid arthritis patients.ConclusionGreater mean SDAI is associated with higher risk of dislocation, infection and composite postoperative complications after total hip arthroplasty in rheumatoid arthritis patients. These patients show a significantly higher rate of postoperative complications than osteoarthritis patients, likely reflecting the influence of systemic inflammation. Disease activity should be reduced as much as possible in rheumatoid arthritis patients before they undergo total hip arthroplasty.

Efficacy and Safety of Bimekizumab in Patients With Psoriatic Arthritis With or Without Methotrexate: 52-Week Results From Two Phase 3 Studies.

The objective of this study was to assess 52-week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/-MTX) treatment at baseline. We conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi-IR]), and the BE VITAL open-label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo-randomized patients received bimekizumab. Missing data were imputed using non-responder imputation, multiple imputation, or worst-category imputation. Through Week 52, similar proportions of bimekizumab-treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and -MTX (BE OPTIMAL: 54.4% +MTX, 54.7% -MTX; BE COMPLETE: 56.3% +MTX, 48.0% -MTX). Similar proportions of bimekizumab-treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and -MTX groups. Similar trends were seen in placebo/bimekizumab-treated patients. Through Week 52, the proportion of bimekizumab-treated patients with ≥1 treatment-emergent adverse event were similar between the +MTX and -MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab. Treatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD-naïve and TNFi-IR patients with PsA and was well tolerated, irrespective of concomitant MTX.