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Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥ 1 biologic disease-modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2. Methods Pts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks; PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient’s assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information; however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to ≥ 1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension. Disclosure P.J. Mease: Consultancies; Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB. Grants/research support; Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB. A. Setty: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. K. Papp: Consultancies; Consultant of: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche. Member of speakers’ bureau; Speakers bureau: AbbVie, Akros, Allergan, Almirall, Amgen, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, Janssen, Kyowa. Grants/research support; Grant/research support from: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, G. F. Van den Bosch: Consultancies; Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB. S. Tsuji: Consultancies; Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, and UCB. Grants/research support; Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, and UCB. M. Keiserman: Consultancies; Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB. Grants/research support; Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB. X. Bu: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. L. Chen: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. R. Mccaskill: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. E. Mcdearmon-Blondell: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. P. Wung: Shareholder/stock ownership; Financial Disclosures: Employee of AbbVie and may hold stock or options. W. Tillett: Consultancies; Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, MSD, Novartis, Pfizer, and UCB. Member of speakers’ bureau; Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Grants/research support; Grant/research support from: AbbVie, Celgene, Eli Lilly, and Janssen.

The purpose of this study was to clarify the clinical characteristics of spondyloarthritis (SpA) patients with inflammatory bowel disease (IBD) compared to those without IBD. Furthermore, among patients with SpA and IBD, we aimed to clarify what clinical characteristics lead rheumatologists to diagnose "IBD-related arthritis." Utilizing SpA and psoriatic arthritis (PsA) patients' data from an international, cross-sectional, observational study, we analyzed information on demographics and disease characteristics, dichotomizing patients by IBD status. The presence or absence of IBD was determined based on data collection of treating rheumatologists. Patients with SpA (including PsA) and IBD were also categorized based on treating rheumatologists' definitive diagnosis in regard to SpA type, and compared by whether the patients had IBD-related arthritis or not. Among 4465 SpA patients, 287 (6.4%, 95%CI 5.7-7.2%) were identified with IBD. Compared to SpA patients without IBD, patients with SpA and IBD had a longer diagnostic delay (5.1 vs. 2.9 years, p 0.001). In patients with SpA and IBD, 111 (38.7%, 95%CI 33.0-44.6%) were diagnosed with IBD-related arthritis. Multivariable analyses showed that HLA-B27 positivity [OR = 0.35, (95%CI 0.15-0.80)], psoriasis [OR = 0.14, (95%CI 0.04-0.50)], IBD as first symptom of SpA [OR = 3.32, (95%CI 1.84-6.01)], and need for IBD-specific treatment [OR = 5.41, (95%CI 2.02-14.50)] were independently associated with the definitive diagnosis of IBD-related arthritis. Collaboration with gastroenterologists is needed to shorten the diagnostic delay in patients with SpA and IBD. The recognition of the factors for the diagnosis of "IBD-related arthritis" may lead to the elucidation of the pathogenesis.

Objective To investigate the influence of nutritional status on severe infection complications in patients with rheumatoid arthritis (RA) Methods This retrospective cohort study on 2108 patients with RA evaluated the prognostic nutritional index (PNI) as an index of nutritional status. Patients were classified into the high or low PNI group according to the cutoff PNI value (45.0). Based on propensity score matching analysis, 360 patients in each group were selected for comparing the incidence of serious infection, clinical findings, and PNI scores. Results The incidence of infection was significantly higher in the low PNI group than in the high PNI group (p Conclusions Patients with RA and malnutrition had a higher incidence of severe infection; thus, evaluating and managing nutritional status is necessary for the appropriate and safe treatment of elderly patients with RA.

Although concurrent occurrence of spondyloarthritis (SpA) and ulcerative colitis (UC) is sometimes seen, the profiles of cytokines have been poorly understood in UC-associated SpA. We herein report a case of UC-associated SpA successfully treated with infliximab. Profiles of cytokines in the serum and colonic mucosa were characterized by an enhanced expression of IL-6 but not TNF-α. Successful induction of remission by infliximab was associated with the downregulation of IL-6 expression but no significant alteration in TNF-α expression. These findings suggest that some cases of UC-associated SpA might be driven by IL-6, and infliximab might be effective in cases lacking enhanced TNF-α responses.

Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO) syndrome is a rare inflammatory osteoarticular disorder, which encompassed many diseases, including pustulotic arthro-osteitis (PAO). Musculoskeletal manifestations, including osteitis, synovitis, and hyperostosis, are the hallmarks of the SAPHO syndrome and affect a variety of regions of the body. Recent survey indicated that more than 80% of cases of SAPHO syndrome in Japan were PAO, originally proposed by Sonozaki et al. in 1981, whereas severe acne was the most commonly reported skin ailment amongst participants with SAPHO syndrome in Israel. Prevalence of SAPHO syndrome remains unavailable, whereas the prevalence of palmoplantar pustulosis (PPP) was reported to be 0.12% in Japan, and 10–30% of patients with PPP had PAO. SAPHO syndrome and PAO are predominantly found in patients in the third through fifth decades of life, and a female predominance is seen in both groups. The diagnosis is typically made by a rheumatologist or dermatologist. Identification of a variety of the clinical, radiological, and laboratory features outlined, as well as diagnostic criteria, are used to make the diagnosis. Goals of treatment seek to maximize health-related quality of life, preventing structural changes and destruction, and normalizing physical function and social participation. Finally, we review the non-pharmacological and pharmacological managements.

Marked varus or valgus hindfoot deformities in 3 patients with ankle osteoarthritis or rheumatoid arthritis were treated by corrective surgery using total ankle arthroplasty or distal tibia oblique osteotomy. All cases achieved not only sufficient correction and satisfactory clinical/radiographic hindfoot improvement but also improvements in both knee alignment and function.Corrective surgery for hindfoot deformity can potentially change or improve ipsilateral knee alignment and function, representing an unexpected benefit of hindfoot realignment.

Increasing of intermetatarsal angle between the first and second metatarsals (M1-M2A) has been reported as a risk factor for recurrence of hallux valgus (HV) deformity, on the other hand, increasing of intermetatarsal angle between the second and fifth metatarsals (M2-M5A) has been reported as a risk factor for resubluxation of the metatarsophalangeal (MTP) joint of the lesser toe after rheumatoid forefoot surgery. In this study, parameters related to increasing M2-M5A were investigated, as compared with M1-M2A and M1-M5A.Radiographic parameters including M1-M2A, M1-M5A, and M2-M5A were retrospectively evaluated for 119 lower limbs from 68 patients with rheumatoid arthritis (RA). To clarify the clinical importance of these intermetatarsal angles, relationships with results from the timed up-and-go (TUG) test were also investigated.M1-M5A showed no correlation with mid-hind foot parameters, whereas M1-M2A and M2-M5A correlated with valgus/varus parameters. An increased M1-M2A was associated with lateral shift of the loading axis in the tibial plafond, whereas an increased M2-M5A was associated with medial shift, but M1-M5A showed no associations. M2-M5A/M1-M2A was significantly lower (1.7) in the normal TUG group than in the delayed TUG group (2.8) (p=0.045).Different patterns of spread are seen for the forefoot. One has a predominantly increased M1-M2A with lateral shift of the loading point in the tibial plafond, whereas the other has a predominantly increased M2-M5A with medial shift of the loading point in the tibial plafond. M2-M5A also should be calculated, and M2-M5A/M1-M2A might be meaningful in understanding physical mobility in RA patients.

This study investigated modified scarf osteotomy as a salvage procedure after resection arthroplasty or silicone implant arthroplasty to preserve mobility of the first metatarsophalangeal (MTP) joint after hallux valgus surgery in patients with rheumatoid arthritis (RA). We investigated three feet with rheumatoid forefoot deformities that showed recurrence of forefoot deformity or breakage of the implant after resection or silicone implant arthroplasty in the first MTP joint. All feet were treated using modified scarf osteotomy with capsular interposition. All cases achieved obvious correction after modified scarf osteotomy despite resection of the first MTP joint and consequently showed both radiographic and clinical improvements. Modified scarf osteotomy offers potential as a definitive salvage procedure after resection arthroplasty or silicone implant arthroplasty for forefoot deformity in patients with RA, because the procedure can realign the first MTP joint obviously with preservation of the range of motion. Concomitant medial capsular interposition into the newly formed first MTP joint is also recommended where possible, to protect the edges of the proximal basal phalanx and distal first metatarsal and also to smoothen the motion of newly formed first MTP joint.

Background When soft tissue balance is not acceptable at total ankle arthroplasty (TAA) for rheumatoid varus deformity, medial malleolar osteotomy has been performed. At the same time, the shape of the ankle joint changes after soft tissue balancing with such an osteotomy, however there is few information for the radiographic findings after the osteotomy. Thus, radiographic changes in the coronal view of such cases were investigated. Methods JSSF-RA foot and ankle scale and SAFE-Q scores were determined along with pre/postoperative radiographic parameters of the ankle joint in 70 ankles (65 patients) with rheumatoid arthritis followed for a mean of 7.9 years (range, 2–16 years) after TAA. Seven ankles were excluded because those underwent lateral or lateral/medial malleolar osteotomy. Twenty-seven ankles underwent medial malleolar osteotomy, and compared with 36 ankles without osteotomy. Results All ankles achieved bone union after medial malleolar osteotomy, and the tibial medial malleolus (TMM) angle was significantly decreased [30.3°–19.1°] following significant valgus correction [TC angle: −2.7° to 0.5°]. The gap due to medial soft tissue tightness was significantly improved by medial malleolar osteotomy [4.95° to 0.7°]. Lateral malleolar fractures sometimes occurred (19%: 5/27 ankles) at valgus correction, but they healed completely without any internal fixation. Conclusion Medial malleolar osteotomy was useful in rheumatoid varus ankle for not only controlling the soft tissue balance, but also providing a stabilized shape of the ankle joint. Lateral malleolar fractures were caused by valgus correction following medial malleolar osteotomy in some cases, but all fractures were completely healed without any internal fixation.

Introduction This study aimed to investigate the current practice in the diagnosis and treatment of SAPHO syndrome among the international rheumatology and dermatology communities. Methods We conducted an electronic survey among the members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the Japan Spondyloarthritis, and Israeli Societies of Rheumatology. Results A total of 78 physicians participated in the survey: rheumatologists (83%, n = 65), dermatologists (11.5%, n = 9), and orthopedics (3.8%, n = 3). SAPHO was considered a subtype of spondyloarthritis by 48.7% (n = 38), a subtype of psoriatic arthritis by 19.2% (n = 15), a separate entity by 25.6% (n = 20), and a subtype of reactive arthritis by 6.4% (n = 5). Palmoplantar pustulosis was the most prevalent cutaneous manifestation (n = 44, 56.4%) and anterior chest pain—the most prevalent osteoarticular manifestation (n = 66, 84.6%). The majority (84.6%, n = 66) voted for the update of the present diagnostic criteria by Khan 1994. Magnetic resonance imaging was considered the preferred imaging modality for the diagnosis of SAPHO by 41% (n = 32). Conduction of bone biopsy for diagnosis of non-infectious osteitis was supported only by 10.3% (n = 8). Patient-reported outcomes were considered the most appropriate measure for the assessment of disease activity by 47.4% (n = 37). The treatment approach was overall similar among the rheumatology and dermatology communities, including non-steroidal anti-inflammatory drugs, bisphosphonates, conventional disease-modifying anti-inflammatory drugs, and biologics. Conclusions Our study underlines the controversy on diagnosis and treatment of SAPHO syndrome among specialists in rheumatology and dermatology and emphasizes an unmet need for update and validation of diagnostic criteria and treatment approach.

Novel biomarkers of rheumatoid arthritis (RA), in addition to antibodies against cyclic citrullinated peptides, are required. Metabolome analysis is a promising approach to identify metabolite biomarkers for clinical diagnosis. We adopted a comprehensive non-targeted metabolomics approach combining capillary electrophoresis time-of-flight mass spectrometry (TOFMS) and liquid chromatography TOFMS. We constructed metabolomics profiling of 286 plasma samples of a Japanese population [92 RA patients, 13 systemic lupus erythematosus (SLE) patients and 181 healthy controls). RA case–control association tests showed that seven metabolites exhibited significantly increased levels in RA samples compared with controls (P < 1.0 × 10−4; UTP, ethanolamine phosphate, ATP, GDP, ADP, 6-aminohexanoic acid and taurine), whereas one exhibited a decreased level (xanthine). The plasma levels of these eight metabolites were not significantly different between seropositive and seronegative RA patients (P > 0.05; n = 68 and 24, respectively). The four nucleotide levels (UTP, ATP, GDP and ADP) were significantly higher in the non-treatment patients in comparison between patients with and without treatment (P < 0.014; n = 57 and 35, respectively). Furthermore, we found that none of the four nucleotide levels showed significant differences in SLE case–control association tests (P > 0.2; 13 patients with SLE and the 181 shared controls) and psoriatic arthritis (PsA) case–control association tests (P > 0.11; 42 patients with PsA and 38 healthy controls), indicating disease specificity in RA. In conclusion, our large-scale metabolome analysis demonstrated the increased plasma nucleotide levels in RA patients, which could be used as potential clinical biomarkers of RA, especially for seronegative RA., Plasma nucleotide levels are new biomarkers for RA

Second-generation bicruciate stabilized (BCS) total knee arthroplasty (TKA) was developed to substitute both anterior and posterior cruciate ligaments and replicate physiological kinematics. This study aimed to evaluate if the postcam mechanism and the surface geometry function effectively. Seventeen and twelve knees implanted with BCS TKA and posterior stabilized (PS) TKA, respectively, were analyzed. In vivo kinematics during deep knee flexion were estimated from single-plane fluoroscopic images using a 2-dimensional to 3-dimensional image registration technique. Flexion angle, anteroposterior translation, femoral external rotation (ER), and postcam engagement were compared between the groups. Postoperative 2011 Knee Society Score (KSS) was obtained at the last follow-up. The medial femoral condyle in BCS was positioned more anteriorly than that in PS from minimum flexion to maximum flexion. Posterior motion of the lateral femoral condyle was observed in both groups. ER of BCS was significantly larger compared to PS from minimum flexion to 100°. However, the amount of ER from minimum flexion to maximum flexion was similar: 6.2° ± 4.5° and 7.7° ± 4.1° in BCS and PS, respectively (P = .364). Anterior postcam engagement was observed in 76.5% and 25.0% in BCS and PS, respectively (P = .006). Posterior postcam engagement was observed in all cases in BCS and PS. There were no significant differences in KSS between the groups. The kinematic differences were likely a result of variations in articular surface geometry.

To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation.In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (Changes in LS BMD at 1.5 years after final DMAb administration were -2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required.

Ankylosing midfoot inversion deformities in 3 patients with rheumatoid arthritis (RA) treated by midfoot derotational osteotomy to remove the pain due to excessive loading of the fifth metatarsal base and to obtain the plantigrade position are presented. All cases achieved sufficient correction and good clinical and radiographic improvement.Midfoot derotational osteotomy seems useful and has the possibility to be a definitive surgical procedure for ankylosing inversion deformity in patients with RA. Osteotomy should be performed from both medial and lateral sides, and careful retraction of soft tissues should always be kept in mind.

Foot/ankle problems remain important issues in rheumatoid arthritis (RA) patients. Although forefoot deformity generally takes a major place in surgical treatment, concomitant mid-hindfoot deformity is also commonly seen. In this situation, it can be easy to overlook that mid-hindfoot deformity can also induce or exacerbate clinical problems behind the forefoot events. Thus, the relationship between mid-hindfoot deformity/destruction and physical activity/ADL was investigated. Radiographic findings of 101 lower limbs (59 patients) were retrospectively evaluated. Alignment parameters in the lower extremity and joint destruction grade (Larsen grade) were measured. The timed-up-and-go (TUG) test, modified health assessment questionnaire (mHAQ), pain, self-reported scores for the foot and ankle (SAFE-Q), and RA disease activity were investigated to assess clinical status. The relationships among these parameters were evaluated. Subtalar joint destruction was correlated with TUG time (r = 0.329), mHAQ score (r = 0.338), and SAFE-Q: social functioning (r = 0.332). TUG time was correlated with the HKA (r = −0.527), talo-1st metatarsal angle (r = 0.64), calcaneal pitch angle (r = −0.433), M1-M5A (r = −0.345), and M2-M5A (r = −0.475). On multivariable linear regression analysis, TUG time had a relatively strong correlation with the talo-1st metatarsal angle (β = 0.452), and was negatively correlated with calcaneal pitch angle (β = −0.326). Ankle joint destruction was also correlated with TUG time (β = 0.214). Development of structural problems or conditions in mid-hindfoot, especially flatfoot deformity, were related with decreased physical activity in RA patients. Wearing an insole (arch support) as a preventative measure and short foot exercise should be considered from the early phase of deformity/destruction in the mid-hindfoot in the management of RA.

ObjectivesTo delineate characteristics of non-radiographic axial spondyloarthritis (nr-axSpA) in Asia versus non-Asian regions, and compare radiographic axSpA (r-axSpA) with nr-axSpA within Asia.MethodsData were collected from the Assessment of SpondyloArthritis international Society-COMOrbidities in SPondyloArthritis database. Categorising patients by region, we compared clinical characteristics between nr-axSpA from Asia vs elsewhere (Europe, the Americas and Africa). Within Asians, we additionally compared patient characteristics of those with nr-axSpA versus r-axSpA.ResultsAmong 3984 SpA cases, 1094 were from Asian countries. Of 780 axSpA patients in Asia, 112 (14.4%) had nr-axSpA, less than in non-Asian countries (486/1997, 24.3%). Nr-axSpA patients in Asia were predominantly male (75.9% vs 47.1%), younger at onset (22.8 vs 27.8 years) and diagnosis (27.2 vs 34.5 years), and experienced less diagnostic delay (1.9 vs 2.9 years) compared with nr-axSpA in non-Asian countries. Nr-axSpA in Asia exhibited higher human leucocyte antigens-B27 prevalence (90.6% vs 61.9%), fewer peripheral SpA features (53.6% vs 66.3%) and similar extra-articular and comorbid disease rates compared with those with nr-axSpA in non-Asian countries. Disease activity, functional impairment and MRI sacroiliitis were less in nr-axSpA in Asia, with higher rates of non-steroidal anti-inflammatory drug response and less methotrexate and biological disease-modifying antirheumatic drugs use. Within Asia, r-axSpA showed higher disease activity and structural damage compared with nr-axSpA, with no differences in other features.ConclusionAmong axSpA, lower frequency of nr-axSpA was observed in Asia. Our results offer an opportunity to better understand clinical characteristics and optimise diagnostic strategies, such as ensuring access and availability of MRI resources for accurate diagnosis of nr-axSpA in Asia.

Objective This nationwide study aimed to reveal the prevalence of ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-ax SpA), and the positivity rate of human leukocyte antigen (HLA) among such patients in Japan. Methods The first survey was conducted in 2221 randomly selected facilities (26.3%) in September 2018, where the patients with AS/nr-ax SpA were taken care of from January to December 2017. We estimated the total number of these patients using response and extraction rates. A second survey was conducted in 117 facilities (49.8%) to assess for HLA-B27 positivity rate and clinical features. Results The estimated total numbers of the patients with AS and nr-ax SpA were 3200 (95% confidence interval [CI]: 2400–3900) and 800 (530–1100), suggesting that the prevalence values of AS and nr-ax SpA in general population were 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. Although 55.5% (76/137) of patients with AS were HLA-B27-positive, those whose age of onset was estimated to be over 50 years tended to undergo less HLA-B27 testing. Conclusion This study revealed the lower prevalence of AS/nr-ax SpA in Japan, compared to those in other countries. Further studies are required to reveal the association of HLA-B27 with the clinical features.

Objective.To delineate clinical characteristics of patients with spondyloarthritis (SpA) in Japan in comparison to other areas of the world.Methods.Using the ASAS-COMOSPA (Assessment of Spondyloarthritis international Society–COMOrbidities in SPondyloArthritis) data, an international cross-sectional observational study of patients with SpA, we analyzed information on demographics, disease characteristics, comorbidities, and risk factors. Patients were classified by region: Japan, other Asian countries (China, Singapore, South Korea, Taiwan), and non-Asian countries (Europe, the Americas, Africa). Patient characteristics, including diagnosis and treatment, were compared.Results.Among 3984 patients included in the study, 161 were from centers in Japan, 933 from other Asian countries, and 2890 from other regions. Of patients with SpA in Japan, 42 (26.1%) had peripheral SpA, substantially more than in other countries. This trend was explained by the predominance of psoriatic arthritis (PsA) among Japanese patients with SpA. In contrast to the relatively low number in Japan, 54% of patients from other Asian countries had pure axial SpA (axSpA) without peripheral features. HLA-B27 testing, considered an integral part of the classification of axSpA, was performed in only 63.6% of Japanese patients with axSpA. More than half of Japanese patients with axSpA were classified using imaging criteria.Conclusion.In our study, there was a more substantial number of peripheral SpA cases observed in Japan compared to other parts of Asia and other regions of the world. Aside from ethnic differences, increasing recognition of PsA in Japan, as well as a potential underdiagnosis of axSpA due to the insufficient use of HLA-B27 testing, may partly explain regional discrepancies.

Background Despite the high incidence of spondyloarthritis (SpA) as an extra-intestinal manifestation of Crohn's disease (CD), the immunopathogenesis of CD-associated SpA remains largely unknown. Objective We tried to explore molecular mechanisms accounting for the development of CD-associated SpA in a patient successfully treated with infliximab. Methods Peripheral blood mononuclear cells (PBMCs) before infliximab treatment were stimulated with Toll-like receptor (TLR) ligands to measure pro-inflammatory cytokine responses. Endoscopic biopsy samples before and after infliximab treatment were subjected to quantitative polymerase chain reaction. Results PBMCs from this CD-associated SpA patient exhibited higher production of pro-inflammatory cytokines upon stimulation with TLR ligands than PBMCs from healthy controls. Induction of remission by infliximab was associated with the downregulation of pro-inflammatory cytokine responses in the small intestinal mucosa, which is continually exposed to TLR ligands. Conclusions Excessive pro-inflammatory cytokine responses to TLR ligands might underlie the immunopathogenesis of CD-associated SpA.

Background Arthrodesis of the first metatarsophalangeal (MTP) joint has been recommended for severe hallux valgus deformity in patients with rheumatoid arthritis (RA). However, with the progress of medical treatment of RA, joint preservation surgery has recently been performed. The aim of this study was to investigate the clinical and radiographic outcomes of modified Scarf osteotomy with medial capsule interposition for RA cases including severe destruction of the first MTP joint and to evaluate risk factors for recurrence. Methods A retrospective observational study of 76 cases (60 patients) followed for a mean of 35.3 months (range, 24 to 56 months) after a modified Scarf osteotomy was performed. Scores on the Japanese Society for Surgery of the Foot (JSSF) RA foot and ankle scale, the JSSF hallux scale, and a self-administered foot evaluation questionnaire (SAFE-Q) were determined along with preoperative and postoperative radiographic parameters. Results There was a significant improvement, from preoperatively to final follow-up, in the mean JSSF RA foot and ankle score (from 52.2 to 76.9 points) and the mean JSSF hallux score (from 38.2 to 74.5 points). There was a recurrence (hallux valgus angle [HVA] of >20°) in 12 feet (16%). The preoperative DAS28-CRP score (disease activity score [based on 28 joints in the body]-C-reactive protein score) and intermetatarsal angles between the first and second metatarsals (M1M2A) and between the first and fifth metatarsals (M1M5A) were significantly greater in the recurrence group, as were the HVA, M1M2A, M1M5A, and Hardy grade at 3 months after surgery. There was a significant negative correlation between the preoperative DAS28-CRP score and the JSSF RA foot and ankle score at final follow-up (β = -0.39, p = 0.02) and a significant positive correlation between the preoperative DAS28-CRP score and the HVA at final follow-up (β = 0.44, p = 0.001). Conclusions The modified Scarf osteotomy with medial capsule interposition for hallux valgus deformity improved clinical and radiographic outcomes in RA cases with severe destruction of the first MTP joint. Increased preoperative M1M2A and M1M5A; incomplete reduction of the sesamoid bone; and the HVA, M1M2A, and M1M5A at 3 months after surgery should be evaluated as they are associated with recurrence of the deformity. The preoperative DAS28-CRP score was associated with the clinical and radiographic outcomes after surgery. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Advances in drug therapy for rheumatoid arthritis (RA) have been encouraging us to preserve the metatarsopharangeal (MTP) joint in correction of forefoot deformities, and original metatarsal shortening offset osteotomy was recommended as one of the conventional surgical options for forefoot deformities in RA cases. The objective of this study was to evaluate short- to mid-term outcomes of modified metatarsal shortening offset osteotomy.A retrospective observational study was completed for 80 RA cases (mean follow-up period: 3.2 years) who underwent modified metatarsal shortening offset osteotomy. Both lesser toe scales and RA foot ankle scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and a postoperative self-administered foot evaluation questionnaire (SAFE-Q) at final follow-up was also checked to evaluate clinical outcomes.This procedure significantly improved clinical scores of both the JSSF [lesser toes and RA foot and ankle] scales. Of 80 feet, 24 (30%) showed recurrence of MTP joint subluxation/dislocation. Furthermore, the feet in the recurrence group showed significant varus hindfoot. On the other hand, valgus foot in the recurrence group more frequently included midfoot bony ankyloses. All of the affected feet showed the limitation of MTP joints (70°) after surgery.Modified metatarsal shortening offset osteotomy was recommended for RA forefoot disorders as one of the joint preservation surgeries in short- to mid-term follow-up. However, some modifications to avoid limitation of ROM in the MTP joint are required. It must be borne in mind that varus hindfoot and/or bony ankyloses in the mid-hindfoot can cause recurrence of dorsal dislocation/subluxation of the lesser toe MTP joint.

Objective.To investigate whether abatacept (ABA) causes more adverse events (AE) than conventional synthetic disease-modifying antirheumatic drugs (csDMARD) after orthopedic surgery in patients with rheumatoid arthritis (RA).Methods.A retrospective multicenter nested case–control study was performed in 18 institutions. Patients receiving ABA (ABA group) were matched individually with patients receiving csDMARD and/or steroids (control group). Postoperative AE included surgical site infection, delayed wound healing, deep vein thrombosis or pulmonary embolism, flare, and death. The incidence rates of the AE in both groups were compared with the Mantel-Haenszel test. Risk factors for AE were analyzed by logistic regression model.Results.A total of 3358 cases were collected. After inclusion and exclusion, 2651 patients were selected for matching, and 194 patients in 97 pairs were chosen for subsequent comparative analyses between the ABA and control groups. No between-group differences were detected in the incidence rates of each AE or in the incidence rates of total AE (control vs ABA: 15.5% vs 20.7% in total, 5.2% vs 3.1% in death).Conclusion.Compared with csDMARD and/or steroids without ABA, adding ABA to the treatment does not appear to increase the incidence rates of postoperative AE in patients with RA undergoing orthopedic surgery. Large cohort studies should be performed to add evidence for the perioperative safety profile of ABA.

Background:Clinical characteristics of nonradiographic axial spondyloarthritis (nr-ax-SpA) are highly variable across patients, and may potentially vary across patient populations, particularly due to differing distributions of human leukocyte antigens (HLA) and other genetic factors. The majority of nr-ax-SpA studies have been conducted in Europe, the United States, and small studies are reported from Asia [1].Objectives:To delineate clinical characteristics of patients with nr-ax-SpA in Asian countries in comparison to other areas of the world.Methods:Utilizing the ASAS-COMOSPA data, an international cross-sectional observational study of SpA patients, we analyzed information on demographics, disease characteristics, comorbidities, and risk factors. Patients were classified by region: Asia (China, Japan, Singapore, South Korea, and Taiwan), and non-Asian countries (Europe, Americas, and Africa); patient characteristics, including diagnosis and treatment, were compared.Results:Among 3984 SpA patients included in the study, 1094 were from centers in Asian countries, and 2890 from other regions. 112/780 (14.4%) of axial SpA patients in Asian countries were nr-ax-SpA, substantially less than in other countries (486/1997, 24.3%). Nr-ax-SpA patients in Asian countries compared to nr-ax-SpA in other countries were more likely male (75.9 vs 47.1%), have onset (22.8 vs 27.8 years) and diagnosis (27.2 vs 34.5 years) at younger age, and experience less diagnostic delay (1.88 vs 2.92 years) (Table 1). Nr-ax-SpA patients in Asian countries have higher prevalence of positive HLA-B27 (90.6% vs 61.9%) and fewer peripheral signs such as arthritis, enthesitis, or dactylitis (53.6% vs 66.3%) but have similar rate of extra-articular manifestations (psoriasis, IBD, or uveitis) and co-morbidities. Disease activity, functional impairment, and inflammation on MRI were less in nr-ax-SpA patients in Asian countries. NSAIDs response was higher and use of methotrexate and b-DMARDs were lower among nr-ax-SpA in Asian countries.Conclusion:Among axial SpA patients, substantially lower frequency of nr-ax-SpA was observed in Asian countries compared to other regions of the world. Nr-ax-SpA patients in Asian countries were predominantly male, and had younger disease onset with higher HLA-B27 positivity rate and less peripheral signs, and better response to NSAIDs. These results offer an opportunity to improve both early diagnosis and treatment of nr-ax-SpA patients in Asian countries.Table 1.Characteristics of nonradiographic axial SpA in Asia versus non-Asian regionsVariablesAsianon-Asian regionsp valueN112486Age at disease diagnosis, yrs27.2 [21.1, 39.6]34.5 [27.7, 41.7]Diagnostic delay, yrs1.88 [0.27, 5.56]2.92 [0.59, 9.58]0.011Male (%)85 (75.9)229 (47.1)Sacroiliitis on MRI among tested (%)49 (67.1)341 (82.2)0.005HLA B27 positivity among measured (%)96 (90.6)273 (61.9)Inflammatory Back Pain (%)107 (95.5)478 (98.4)0.076Arthritis, enthesitis, or dactylitis (%)60 (53.6)322 (66.3)0.016Psoriasis (%)12 (10.7)82 (16.9)0.142Uveitis (%)20 (17.9)81 (16.7)0.870Inflammatory bowel disease (%)5 (4.5)27 (5.6)0.817Elevated CRP (%)37 (33.0)213 (43.8)0.048Physician global assessment (0-10)2.0 [1.0, 5.0]2.0 [1.0, 4.0]0.741Patient global assessment (0-10)3.0 [1.0, 6.0]4.0 [2.0, 6.0]0.012ASDAS-CRP1.40 [0.95, 2.08]1.97 [1.21, 2.78]BASFI0.8 [0.05, 2.65]2.9 [0.8, 5.6]Good response to NSAIDs (%)80 (71.4)272 (56.0)0.004Methotrexate use (%)18 (16.1)134 (27.6)0.016Biological DMARDs use (%)27 (24.1)191 (39.3)0.004References:[1]López-Medina C, Ramiro S, van der Heijde D, et al. Characteristics and burden of disease in patients with radiographic and non-radiographic axial Spondyloarthritis: a comparison by systematic literature review and meta-analysis. RMD Open. 2019 Nov 21;5(2): e001108.Acknowledgements:This study was conducted under the umbrella of the International Society for Spondyloarthritis Assessment (ASAS) and COMOSPA study was supported by unrestricted grants from Pfizer, AbbVie and UCB.Disclosure of Interests:Keisuke Ono: None declared, Mitsumasa Kishimoto Speakers bureau: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Sho Fukui: None declared, Satoshi Kawaai: None declared, Gautam A. Deshpande: None declared, Kazuki Yoshida Consultant of: OM1, Inc., Grant/research support from: Corrona, LLC, Naomi Ichikawa: None declared, Yuko Kaneko Speakers bureau: AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, and UCB, Taku Kawasaki: None declared, Kazuo Matsui: None declared, Mitsuhiro Morita: None declared, Kurisu Tada: None declared, Naoho Takizawa: None declared, Naoto Tamura: None declared, Atsuo Taniguchi: None declared, Yoshinori Taniguchi: None declared, Shigeyoshi Tsuji: None declared, Shigeto Kobayashi: None declared, Masato Okada: None declared, Clementina López-Medina: None declared, Anna Moltó Consultant of: AbbVie, Pfizer, MSD, Novartis, Gilead, Lilly and UCB, Grant/research support from: AbbVie, Pfizer, MSD, Novartis, Gilead, Lilly and UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Employee of: Imaging Rheumatology bv. (Director), Maxime Dougados: None declared, Yoshinori Komagata: None declared, Tetsuya Tomita: None declared, Shinya Kaname: None declared.

Level of Evidence: Level V.

Objectives: To evaluate the effectiveness of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA) who showed an inadequate response to tocilizumab (TCZ), especially patients who were ...

Adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, was retrospectively evaluated for its effect on musculoskeletal manifestations and health-related quality of life in patients with psoriatic arthritis (PsA) during daily clinical practice.Patients who initiated adalimumab therapy after March 2010 were followed for at least 24 weeks with the clinical outcome measures. Eleven patients, all men with a mean age of 45.4 years, had mean psoriasis durations of 16.2 and 8.4 years at baseline.After 24 weeks, 72.7, 63.6, and 45.5 % of the patients met the ACR 20, 50, and 70 response criteria, respectively, while 81.8 % achieved the PsA response criteria. Disease Activity Score using the 28-joint count and CRP declined from 3.2 ± 1.2 at baseline to 1.3 ± 0.4 at week 24 (P0.01). The Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index scores also decreased significantly (both P values were0.01). After 24 weeks, three out of eight dimensions of the Medical Outcomes Study 36-Item Short Form Health Survey and Physical Component Summary were significantly improved (all P values were0.05).Adalimumab exerted its effect as early as week 4, and it was sustained until the end of the 24-week observation period in the PsA patients.

Purpose Tranexamic acid (TXA) reduces blood loss in patients undergoing total knee arthroplasty (TKA). However, few studies have reported the optimum timing and dosage for administration of TXA. The purpose of this study was to evaluate the effect of repeat-dose TXA on blood loss during TKA and the necessity of autologous blood donation or postoperative autotransfusion.

Vacuum-assisted wound closure (VAC) is useful for difficult wound beds, although sites where bleeding or infection is expected are usually regarded as problematic for this therapy. This report outlines the treatment of chronic tibial osteomyelitis (Cierny- Mader type III) due to mixed infection with Nocardia spp and Bacteroi- des fragilis by postoperative VAC therapy direct to the medullary cavity, followed by wound coverage with a gastrocnemius myocutaneous skin flap.A 64-year-old man developed chronic left tibial os- teomyelitis after a work injury. The nonviable tissues were debrided, including a sequestrum. Nocardia spp and B. fragilis were isolated from surgical bone specimens, and chronic tibial osteomyelitis due to mixed infection was diagnosed. Postoperatively, VAC therapy was performed directly to the open medullary cavity of the tibia and sub- sequently covered the residual soft tissue defect with a gastrocnemius myocutaneous flap.The authors could not find any English literature on VAC therapy direct to the medullary cavity combined with transplantation of a myocutaneous flap for osteomyelitis. Nocardia spp can cause a variety of infections, among which osteomyelitis occupies a relatively small percentage.This case raises the possibil- ity of treating chronic tibial osteomyelitis caused by mixed infection with Nocardia spp and B. fragilis by applying postoperative VAC ther- apy directly to the medullary cavity and covering the residual wound with a gastrocnemius myocutaneous flap.

We aimed to evaluate the clinical efficacy of monotherapy with alendronate and combined therapy with alendronate and menatetrenone (vitamin K2 [VitK2]) in postmenopausal rheumatoid arthritis (RA) patients with osteoporosis or osteopenia. Sixty-two postmenopausal RA patients with untreated osteoporosis or osteopenia (lumbar spine bone density ≤80 % of young adult mean [YAM]) were enrolled: 39 had abnormal serum undercarboxylated osteocalcin (ucOC) levels (>4.5 ng/mL) and received combined therapy with alendronate (35 mg/week) and VitK2 (45 mg/day) (ALN + K group); 23 had normal ucOC levels (≤4.5 ng/mL) and received alendronate monotherapy (35 mg/week) (ALN group). The clinical results for the 57 patients in both groups were evaluated after 1-year treatment. The mean baseline/follow-up (FU) lumbar spine bone density (%YAM) values were 73.0/76.8 % (P