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Objective Group‐level analyses from the phase 3 DISCOVER‐2 trial of guselkumab demonstrated robust and durable improvements across psoriatic arthritis (PsA) domains. To specifically evaluate continuous disease control in individual patients, persistence of clinically relevant improvements was assessed, both at consecutive guselkumab dosing visits and over time. Methods Post hoc analyses included biologic‐naïve patients randomized to 100 mg of guselkumab at week 0, week 4, and then every 8 weeks (Q8W). Improvements in joint (minimal clinically important improvement [MCII] in Disease Activity Index for PsA [DAPSA; ≥7.25], clinical DAPSA [cDAPSA; ≥5.7]), skin (Investigator's Global Assessment [IGA] 0/1), and overall disease activity (patient global assessment of arthritis and psoriasis [PtGA Arthritis+Psoriasis; MCII ≥ 15 mm], PsA Disease Activity Score [PASDAS; MCII ≥ 0.8]) were assessed. Proportions of patients with maintenance of DAPSA and cDAPSA MCII at consecutive Q8W guselkumab dosing visits (ie, at weeks 4 and 12, weeks 12 and 20, etc through week 52) and patient‐level durability of response through week 100 (Kaplan‐Meier) were determined. Results Among 248 patients randomized to guselkumab Q8W, 93% to 99% maintained clinical improvement in joint disease at consecutive Q8W dosing visits through week 52 across time periods. Among guselkumab patients achieving MCII by week 24, estimated probabilities of maintenance of clinical improvement 100 weeks post achievement ranged from 68% (IGA 0/1) to 89% (PASDAS MCII). Median times to loss of improvement were not reached; estimated mean weeks of maintenance of improvement were 58.6, 52.4, 75.7, 83.6, and 76.7, respectively, for DAPSA, cDAPSA, IGA, PtGA Arthritis+Psoriasis, and PASDAS. Conclusion Guselkumab provided highly durable patient‐level improvements, both at consecutive Q8W dosing visits for joint disease activity and over time across PsA domains according to physician‐ and patient‐driven assessments.

Abstract Background The efficacy and safety of upadacitinib in patients with ankylosing spondylitis (AS) and inadequate response/intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR) were evaluated through 1 year in the SELECT-AXIS 2 study. Here, we assess 2-year efficacy, safety, and imaging outcomes in SELECT-AXIS 2. Methods Patients who received continuous upadacitinib, and those who switched from placebo to upadacitinib at week 14, could enter the open-label extension (OLE). Efficacy endpoints included Assessment of SpondyloArthritis international Society (ASAS) and Axial Spondyloarthritis Disease Activity Score (ASDAS) responses, and changes from baseline in measures of disease activity, back pain, function, and quality of life. Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). As observed (AO) and AO with non-responder imputation (AO-NRI) analyses were used for binary endpoints; AO with mixed-effects model for repeated measures (AO-MMRM) for continuous endpoints; and AO-analysis of covariance for mSASSS. Treatment-emergent adverse events (TEAEs) in patients receiving ≥ 1 upadacitinib dose through week 104 are presented as events (E)/100 patient-years (PY). Subgroup analyses were performed by prior tumor necrosis factor/interleukin-17 inhibitor exposure and bDMARD lack of efficacy/intolerance. Results Of 420 patients who entered the bDMARD-IR AS study, 409 entered the OLE, and 331 (continuous upadacitinib, n = 163; placebo to upadacitinib, n = 168) completed week 104. Improvements in efficacy measures were sustained through the OLE, with similar response rates between the continuous upadacitinib and placebo to upadacitinib groups at week 104. At week 104, 64.9% and 61.7% of patients, respectively, had achieved ASAS 40% response (AO-NRI). Mean changes from baseline were similar between the two groups at week 104 across measures (ASDAS: -2.1 and -2.0; total back pain: -4.9 and -4.6, respectively; AO-MMRM). Over 93.0% of patients showed no radiographic progression (mSASSS mean change from baseline

Abstract Background Axial spondyloarthritis (axSpA) is a chronic inflammatory disease which mainly affects the spine and sacroiliac joints, causing longstanding back pain, stiffness, and limited mobility. AxSpA is an underrecognized disease in non-rheumatology practices because of its heterogeneous clinical features that may be difficult to identify. Main body Sports medicine practitioners are well positioned to suspect and recognize axSpA among their patients with chronic back pain and refer them to a rheumatologist. Early referral to a rheumatologist is important for timely diagnosis, prompt treatment, and improved long-term outcomes for patients with axSpA. Physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs) remain the first-line treatment for and the cornerstone of axSpA management. For patients with inadequate response to or intolerance of NSAIDs, biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (ts) DMARDs are indicated. These drugs can reduce pain, inflammation, fatigue, and disability and can improve health-related quality of life. The goal of this review is to improve awareness of axSpA among sports medicine practitioners and other non-rheumatologists so that these providers ensure timely referral of patients with suspected axSpA to rheumatologists for appropriate treatment and better outcomes. We also provide an update on current treatment possibilities for axSpA and describe how rheumatologists use treatment guidelines and disease activity measures to identify and optimally treat patients with active axSpA. Conclusion Sports medicine practitioners have an excellent opportunity to identify patients with suspected axSpA and refer them to rheumatologists in a timely manner, as well as monitor symptoms among patients diagnosed with axSpA to identify inadequately controlled disease.

B Truong,1,* N Rich-Garg,2,* BD Ehst,1 AA Deodhar,2 JH Ku,2 K Vakil-Gilani,2 A Danve,2 A Blauvelt,1,3 1Department of Dermatology, Oregon Health and Science University, 2Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, 3Oregon Medical Research Center, Portland, OR, USA *These authors contributed equally to this work Innovation: What is already known about the topic: psoriasis (PsO) is a common skin disease with major impact on quality of life (QoL). Patient-reported data on QoL from large number of PsO patients with and without psoriatic arthritis (PsA) are limited. What this study adds: In a large cohort referred to a university psoriasis center, patients with PsO and concomitant PsA (~30% in this group) had greater degrees of skin and nail involvement and experienced greater negative impacts on QoL. Despite large numbers of patients with moderate-to-severe disease, use of systemic therapy by community practitioners was uncommon. Background: PsO and PsA are common diseases that have marked adverse impacts on QoL. The disease features and patient-reported QoL data comparing PsO and PsA patients are limited. Objective: To identify and compare demographics, clinical disease characteristics, and QoL scores in a large cohort of PsO patients with and without PsA. Methods: All PsO patients seen in a psoriasis specialty clinic, named the Center of Excellence for Psoriasis and Psoriatic Arthritis, were enrolled in an observational cohort. Demographic, QoL, and clinical data were collected from patient-reported questionnaires and from physical examinations performed by Center of Excellence for Psoriasis and Psoriatic Arthritis dermatologists and a rheumatologists. Cross sectional descriptive data were collected and comparisons between patients with PsO alone and those with concomitant PsA are presented. Results: A total of 568 patients were enrolled in the database. Mean age of PsO onset was 28 years and mean disease duration was 18 years. Those with family history had an earlier onset of PsO by ~7 years. Mean body surface area involvement with PsO was 14%. Mean body mass index was 30.7. Prevalence of PsA was 29.8%. PsA patients had a higher mean body surface area compared to patients with PsO alone (16.7% vs 13.4%, P

Abstract Introduction Patterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA). Methods Post hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients. Results Among patients with highly active PsA (baseline cDAPSA = 44.1–45.0, PASDAS = 6.4–6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3–2.5; P

Abstract Introduction There are limited data on the use of advanced therapies to treat psoriatic arthritis (PsA) in Russia. Guselkumab, an interleukin (IL)-23p19-subunit inhibitor, demonstrated efficacy in patients with PsA in the phase 3 DISCOVER-1 and -2, and COSMOS trials. This analysis evaluated the efficacy and safety of guselkumab in patients with PsA in Russia. Methods This post hoc analysis of DISCOVER-1 and -2 included 1002 biologic-naïve patients with active PsA from Russia (n = 317) and the rest of the world (RoW; n = 685). Patients received guselkumab 100 mg every 4 weeks (Q4W), or at week 0 and 4 then Q8W, or placebo then guselkumab Q4W at week 24 (Russian: n = 119, 88, and 110, respectively; RoW: n = 216, 246, and 223, respectively). Outcomes through week 52 were pooled (DISCOVER-1 and -2); outcomes from week 52 to 100 represent DISCOVER-2 only. Results In patients from Russia, ≥ 20% improvement in the American College of Rheumatology (ACR20) criteria response rates were higher with guselkumab vs. placebo at week 24, increased through week 52, and were consistent across all guselkumab-treated groups at week 100. Similar trends were generally observed for ACR50, ≥ 90% improvement in Psoriasis Area and Severity Index (PASI90), achievement of Disease Activity in Psoriatic Arthritis (DAPSA) low disease activity/remission and minimal disease activity, enthesitis and dactylitis resolution, ≥ 0.35 improvement in Health Assessment Questionnaire–Disability Index (HAQ-DI) score, improvement in patient-reported pain, and measures in patients with axial PsA (including Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS], and patient-reported spinal pain). Efficacy responses were similar between patients from Russia and the RoW across all endpoints and timepoints. The safety profile of guselkumab in patients from Russia was consistent with previous findings. Conclusion This analysis demonstrated that the safety and efficacy profiles of guselkumab across all PsA domains and patient-reported outcomes in patients from Russia were similar to those in patients from the RoW. Trial Registration Numbers NCT03162796 and NCT03158285.

Objective Upadacitinib improved the signs and symptoms of non‐radiographic axial spondyloarthritis (nr‐axSpA) versus placebo over 14 weeks in the primary analysis of the SELECT‐AXIS 2 nr‐axSpA study. Here, we evaluated the efficacy and safety of upadacitinib through 1 year in patients with nr‐axSpA in SELECT‐AXIS 2. Methods Patients aged at least 18 years diagnosed with nr‐axSpA who fulfilled the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria and were receiving stable background therapy were randomized to upadacitinib 15 mg once daily or placebo for the 52‐week double‐blind period. Efficacy was assessed using non‐responder imputation incorporating multiple imputation (NRI‐MI) and as‐observed analyses for binary endpoints, and mixed‐effects model repeated measures for continuous endpoints. Results Of 314 randomized patients, 259 (upadacitinib, n = 129; placebo, n = 130) completed 52 weeks of treatment. More patients receiving upadacitinib versus placebo achieved ≥40% improvement in ASAS at week 52 (63% vs 43%, NRI‐MI; nominal P < 0.001). Similar treatment effects were observed for the achievement of axSpA Disease Activity Score inactive disease (33% v 11%, NRI‐MI; nominal P < 0.001). Overall, patients receiving upadacitinib versus placebo showed greater improvement in disease activity, inflammation, pain, function, enthesitis, and quality of life through 52 weeks. Adverse events were generally comparable between the treatment groups. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, inflammatory bowel disease, or deaths were reported in those receiving upadacitinib. Conclusion Treatment with upadacitinib showed sustained efficacy versus placebo with no new safety findings identified through 1 year. These results support the continued favorable benefit–risk profile of upadacitinib treatment for nr‐axSpA.

Clear cell adenocarcinoma (CCAC) of cervix is a rare subtype of endocervical adenocarcinoma that accounts for 4% of all cervical adenocarcinoma with many morphological mimickers. Retrospectively study cases of cervical clear cell adenocarcinoma of the cervix. Clinical profile and pathological features of CCAC of the cervix diagnosed between 2018-2022 were retrospectively analyzed.The database of the Department of Pathology of our institute was systematically searched for patients diagnosed with clear cell adenocarcinoma of the cervix during 2018-2022.A total of 19 patients were studied with the mean age of patients being 53.72 years (range 25 -84 yrs,standard deviation-25.9) and median tumor size being 5.6cm. Lymph node metastasis was identified in 33.3% and distant metastasis were seen in 20% of the cases. Staging could not be done in 4 cases.FIGO staging of the cases included IB1(2 cases), IB2(2 cases), IIB (3 cases),IIIA (1 case)IIIB(4 cases),and IV(3 cases). On histopathological evaluation, heterogeneous architectural pattern comprising of tubulocystic, solid, and papillary patterns were seen in 13 cases (13/19,68.4%). Pure tubulocystic (3/19,15.7%), pure papillary (2/19,10.5%), and pure solid patterns (1/19,5.3%) were also identified. Tumor cells with clear cytoplasm ranged from 5% to 95%. Nuclear atypia was moderate to marked in all the cases (19/19,100%). Mitotic activity varied from 1/10hpf to 20-22/10hpf. By immunohistochemistry, tumor was positive for Napsin A in all the cases,p16INK4a was negative in majority of cases (15/19,78.9%) and ER was negative in 14 cases (14/19,73.7%) .p53 showed wild type staining except for one case . Clear cell adenocarcinoma being a rare subtype of cervical adenocarcinoma, needs to be differentiated from other Human Papilloma Virus(HPV) independent adenocarcinomas (gastric and mesonephric types) and benign entities such as endocervical glandular Arias-Stella reaction. Judicious use of a panel of immunostains is often helpful.

B-cell depletion therapy (BCDT) has been employed to treat autoimmune disease for ~20 years. Immunoglobulin G1 (IgG1) monoclonal antibodies targeting CD20 and utilizing effector function (eg, antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis) to eliminate B cells have historically been the predominant therapeutic approaches. More recently, diverse BCDT approaches targeting a variety of B-cell surface antigens have been developed for use in hematologic malignancies, including effector-function–enhanced monoclonal antibodies, chimeric antigen receptor T-cell (CAR-T) treatment, and bispecific T-cell engagers (TCEs). The latter category of antibodies employs CD3 engagement to augment the killing of target cells. Given the improvement in B-cell depletion observed with CAR-T and TCEs compared with conventional monospecific antibodies for treatment of hematologic malignancies and the recent case reports demonstrating therapeutic benefit of CAR-T in autoimmune disease, there is potential for these mechanisms to be effective for B-cell–mediated autoimmune disease. In this review, we discuss the various BCDTs that are being developed in autoimmune diseases, describing the molecule designs, depletion mechanisms, and potential advantages and disadvantages of each approach as they pertain to safety, efficacy, and patient experience. Additionally, recent advances and strategies with TCEs are presented to help broaden understanding of the potential for bispecific antibodies to safely and effectively engage T cells for deep B-cell depletion in autoimmune diseases.

Aims and Objective: To evaluate the patients at risk of venous thromboembolism (VTE) based on Caprini VTE risk assessment scale and the effect of implementation of this scale on the use of thromboprophylaxis. Materials and Methods: A prospective study was conducted, including patients who underwent major elective surgical procedures. Demographic details were noted, and VTE prophylaxis offered if needed. According to the VTE risk assessment scale, patients were categorised into very low-, low-, moderate-, and high-risk categories. The data were analysed statistically. Results: A total of 500 patients (women = 259; men = 241) were enrolled in this study. Of them, eight women and nine men developed VTE (P = 0.691). The maximum number of patients who developed VTE belonged to 61–70 years group (n = 7). According to VTE risk assessment, 61 patients were categorised as low-risk, 217 patients as moderate-risk, and 222 patients were categorised as high-risk. A significant (P < 0.0005) correlation was found between body mass index (BMI) and VTE development. In obese patients with BMI >25, 14 patients developed VTE. Out of total, 329 patients received prophylaxis for deep vein thrombosis. Of 284 patients who received pharmacologic prophylaxis, only three developed VTE (P = 0.002). Of 145 patients who received mechanical prophylaxis, 75 had high risk and none of them developed VTE. Four patients had mortality, and a significant (P = 0.022) correlation was found between mortality and VTE development. Conclusion: According to Caprini risk assessment scale, the prophylaxis for VTE was effective in patients undergoing major elective general surgery, resulting in significant lowering of morbidity and mortality.

Abstract Background Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in tofacitinib-treated patients with AS. Methods This post hoc analysis used phase 3 trial data from patients with AS receiving tofacitinib 5 mg twice daily or placebo to week (W)16; all patients received open-label tofacitinib W16–48. Outcomes: nocturnal pain; total back pain; fatigue, spinal pain, peripheral joint pain/swelling, enthesitis, and morning stiffness (Bath AS Disease Activity Index [BASDAI] questions 1–6); BASDAI total score; AS Disease Activity Score (ASDAS). Median time to improvement events was estimated using non-parametric Kaplan-Meier models. Improvement events were defined as initial (first post-baseline observation) and continued (sustained for 2 consecutive visits) ≥ 30% and ≥ 50% improvement in back/nocturnal pain or BASDAI questions/total scores, or ASDAS improvement ≥ 1.1 and ≥ 2.0 points. Results 269 patients (tofacitinib: n = 133; placebo-to-tofacitinib: n = 136) were assessed. Median time to improvement was shorter, and more patients experienced improvements with tofacitinib vs. placebo-to-tofacitinib; differences observed from W2 (first post-baseline assessment). Median time to initial (continued) ≥ 30% pain improvement was 4 (4–8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib (8 [8] weeks post-switch). Median time to initial (continued) ≥ 50% improvement of pain, peripheral joint pain/swelling and enthesitis, morning stiffness, BASDAI total score, and fatigue was 8–24 (12–40) weeks with tofacitinib vs. 24–32 weeks (32 weeks–not estimable [NE]) with placebo-to-tofacitinib. Median time to initial (continued) ASDAS improvement ≥ 1.1 points was 4 (8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib, and NE for improvement ≥ 2.0 points with either treatment. Conclusions Improvements in AS core domains occurred more rapidly with tofacitinib vs. placebo-to-tofacitinib. Half of tofacitinib-treated patients with AS will likely experience improvements ≥ 30% in pain and ≥ 1.1 points in ASDAS during month (M)1, ≥ 50% improvement in nocturnal pain and enthesitis by M2, and in morning stiffness by M3. Results show that initiating tofacitinib as soon as possible is associated with quicker improvements in AS core domains vs. delaying treatment. Trial registration ClinicalTrials.gov, NCT03502616, 11 April 2018.

Abstract In this commentary, we review clinical data which helps inform individualized benefit–risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50 years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65 years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients

Abstract Background The transition into residential aged care is frequently associated with a reduction in physical activity, social engagement, and emotional wellbeing. Our aim was to evaluate the impact of a 26-day international cycling competition (Road Worlds Competition for Seniors), incorporating elements of exercise, audiovisual cycling footage, social engagement, and gamification, on the physical, psychological, and social well-being of aged care residents. We aimed to use findings to inform the development of a multi-modal intervention model to maximise wellbeing for older adults. Methods Residents (N = 32) participated in a mixed-methods single-group intervention pilot study that compared pre-and post-competition measures for the following wellbeing domains; physical, psychological, and social. In addition, interviews were conducted with residents (n = 27) and staff (n = 6) to explore their experiences. Results Measures identified significant improvements across multiple wellbeing domains, including functional fitness, depression, self-efficacy, and social network sizes. Findings from the interview data indicated that the multimodal components involved in the program delivery were valued by staff and residents who enjoyed the gamification, audiovisual cycling footage, social engagement, opportunities for reminiscence, and camaraderie between peers, staff, and volunteers. Conclusions Findings highlight a constellation of benefits across physical, psychological, and social domains of wellbeing and inform a model for innovative multidimensional programs in residential aged care. The benefits for residents with varying physical and cognitive abilities support the use of creative strategies that maximise inclusion and engagement for residents.

Sternal wound complications following sternotomy need a multidisciplinary approach in high-risk postoperative cardiac surgical patients. Poorly controlled pain during surgical management of such wounds increases cardiovascular stress and respiratory complications. Multimodal analgesia including intravenous opioids, non-opioid analgesics, and regional anesthesia techniques, like central neuraxial blocks and fascial plane blocks, have been described. Pecto-intercostal fascial plane block (PIFB), a novel technique, has been effectively used in patients undergoing cardiac surgery. Under ultrasound (US) guidance PIFB is performed with the aim of depositing local anesthetic between two superficial muscles, namely the pectoralis major muscle and the external intercostal muscle. The authors report a series of five cases where US-guided bilateral PIFB was used in patients undergoing sternal wound debridement. Patients had excellent analgesia intraoperatively as well as postoperatively for 24 hours with minimal requirement of supplemental analgesia. None of the patients experienced complications due to PIFB administration. The authors concluded that bilateral PIFB can be effectively used as an adjunct to multimodal analgesia with general anesthesia and as a sole anesthesia technique in selected cases of sternal wound debridement.