OBJECTIVE:Herpes zoster (HZ) is a common adverse event associated with Janus kinase inhibitors (JAKi); however, direct comparisons using real-world data are lacking, which we aimed to clarify. METHODS:We retrospectively analyzed data from the multicenter ANSWER cohort, including 1,096 treatment courses from 765 patients with RA (84.1% female; mean age, 63.9 years; mean follow-up, 18.2 months) who initiated treatment with tofacitinib, baricitinib, peficitinib, upadacitinib, or filgotinib. Incidence rates (IRs) of HZ were calculated per 100 patient-years using exact Poisson method. Time-to-event and treatment retention analysis were performed using Kaplan-Meier methods, and hazard ratios (HRs) were estimated using Cox proportional hazards models adjusted for patient characteristics. RESULTS:During follow-up, HZ occurred in 88 treatment courses. The IRs per 100 person-years were 5.84 for tofacitinib, 6.21 for baricitinib, 3.79 for peficitinib, 7.38 for upadacitinib, and 1.73 for filgotinib. In the adjusted Cox model, filgotinib (reference) was associated with a significantly lower hazard of HZ compared with tofacitinib (HR, 7.68; 95% CI, 1.71-34.6; P=0.008), baricitinib (HR, 6.35; 95% CI, 1.48-27.1; P=0.013), and upadacitinib (HR, 4.75; 95% CI, 1.11-20.3; P=0.036), whereas no significant differences were observed in treatment retention. Patient-related variables, including age, sex, prior HZ, and vaccination history, were not significantly associated with HZ risk. CONCLUSION:Filgotinib showed a lower observed risk of HZ compared with tofacitinib, baricitinib, and upadacitinib. Given the limited number of events and observational design, further large-scale studies with longer follow-up are warranted to confirm these findings.

OBJECTIVES:To investigate the effectiveness of denosumab (DMAb), teriparatide (TPTD) and romosozumab (ROMO) in patients with glucocorticoid-induced osteoporosis (GIOP). METHOD:This multicenter, retrospective cohort study employed propensity score matching to select 42 patients per treatment group [92.1% female, mean age 73.5 years, 35.7% osteoporosis treatment naive, oral glucocorticoids (prednisolone equivalent) 5.4 mg/day, baseline bone mineral density (BMD) T-scores: lumbar spine (LS) -2.5]. Bone turnover markers (BTMs) and BMD were assessed over 12 months. RESULTS:DMAb suppressed BTM levels, whereas TPTD increased them. ROMO showed a dual effect, with increased and decreased levels of formation and resorption markers, respectively. At 12 months, LS BMD increases were greater with ROMO (9.5%) and tended to be higher with TPTD (8.4%) compared with DMAb (4.4%) (P = 0.008 for ROMO vs DMAb). At 6 months, total hip BMD increased with DMAb (2.6%) and ROMO (1.8%) but decreased with TPTD (-0.6%; P = 0.01 for DMAb vs TPTD; P = 0.042 for ROMO vs TPTD); no significant differences were observed at 12 months (3.2%, 2.6%, 2.2%, respectively). DMAb showed significant increases in femoral neck BMD at 6 (2.2%) and 12 (3.0%) months from baseline. CONCLUSION:BTM levels reflected expected pharmacological actions of each drug. ROMO showed greater LS BMD gains than DMAb, while TPTD demonstrated a similar response, whereas DMAb may provide earlier benefits at cortical-rich sites. These findings underscore the importance of site-specific, individualized treatment strategies for GIOP.

In recent years, total ankle arthroplasty (TAA) has been increasingly selected for the treatment of ankle arthropathy associated with rheumatoid arthritis because it allows early weight-bearing and preservation of ankle range of motion. However, salvage strategies for talar component subsidence after TAA depend on the implant system used, and ankle arthrodesis is frequently selected for cases treated with the FINE Total Ankle System (NAKASHIMA HEALTHFORCE CO.). Implant removal followed by ankle arthrodesis inevitably results in loss of ankle motion and substantial bone defects. Furthermore, removal of a cemented implant often requires extensive bone debridement, which may further increase the risk of non-union and deterioration of activities of daily living due to prolonged non-weight-bearing. We report a case of talar component subsidence of approximately 10 mm after TAA treated with the FINE Total Ankle System, successfully managed by revision TAA using the largest available talar component (size 6L) combination with bone grafting and medial malleolar osteotomy. This approach preserved ankle range of motion and was associated with favourable mid-term clinical and radiographic outcomes in the present case. Revision TAA using the largest available talar component with bone grafting may be considered a potential salvage option for carefully selected patients with talar component subsidence after TAA using the FINE Total Ankle System.

Aims:Forefoot deformities are common in patients with rheumatoid arthritis (RA) and often impair quality of life. Patient-reported outcome measures (PROMs), including the Self-Administered Foot Evaluation Questionnaire (SAFE-Q), are increasingly used to assess surgical outcomes; however, the preoperative conditions needed to achieve favourable postoperative PROMs remain unclear. This study aimed to identify factors associated with postoperative SAFE-Q scores (mean score across five sub-scales, maximum 100) and determined preoperative cutoff values predictive of achieving predefined postoperative SAFE-Q thresholds (≥ 70 or ≥ 90). Methods:In this multicentre, retrospective case series, 101 feet in 80 patients (including 21 bilateral cases) with RA who underwent forefoot surgery between July 2015 and July 2023 were analyzed (mean age at surgery 65.8 years (SD 10.7); 79 female patients). Inclusion criteria were symptomatic forefoot deformities with available SAFE-Q data pre-surgery and at ≥ one year post-surgery. Procedures included modified scarf osteotomy and offset shortening osteotomies for the metatarsals. SAFE-Q scores, Japanese Society for Surgery of the Foot scores, radiological parameters, and disease activity were evaluated pre- and postoperatively. Multiple regression identified preoperative factors associated with postoperative SAFE-Q scores, and significant variables were further assessed using receiver operating characteristic (ROC) analyses to determine preoperative cutoff values for postoperative SAFE-Q thresholds (≥ 70 and ≥ 90). Results:Postoperatively, the median SAFE-Q score was 84.8 (IQR 73.0 to 92.3), a significant improvement over the preoperative median score of 48.9 (IQR 34.9 to 67.5; p < 0.001). Multivariable analysis showed that older age and lower preoperative SAFE-Q scores were associated with lower postoperative SAFE-Q scores (β -0.286 (95% CI -0.486 to -0.086) and 0.505 (95% CI 0.319 to 0.691), respectively). ROC analysis identified cutoffs of 54.0 for preoperative SAFE-Q (area under the curve (AUC) 0.644) and 70 years for age (AUC 0.722) when predicting a postoperative score ≥ 90. Conclusion:Higher preoperative SAFE-Q scores and younger age at surgery were linked to improved postoperative outcomes. Although their predictive accuracy is limited, these thresholds may help estimate postoperative function and support preoperative counselling and shared decision-making.

Introduction: The meniscus is an essential structure of the knee joint, performing functions such as load transmission, shock absorption, joint stability, and joint lubrication. The deterioration of meniscal function due to trauma or degenerative changes causes meniscal-related symptoms and leads to cartilage damage and osteoarthritis. Current treatments target not the meniscus itself, but the entire knee joint or intra-articular tissues, and non-surgical treatments that directly access the meniscal tissues are not widely used. This study aimed to evaluate the effects of the intrameniscal injection technique on meniscal tissue and cells. Methods: Four healthy porcine menisci and 10 human menisci from patients after total knee arthroplasty were injected with different solutions to investigate the required injection force, intrameniscal distribution of the injected solution, and biological effects on the meniscal cells. The initial force exerted by the syringe piston was measured by a pressure gauge. After the injection of Fast Green FCF solution, the distribution was observed, measured, and analyzed in 3 indicators: Width, Stained Area, and Calculated Volume. Other meniscal tissues were injected with recombinant interleukin-1 beta (rIL-1β), dexamethasone or papain, cultured and harvested for qRT-PCR or histology analysis. Results: Statistically significantly greater force was required for the intrameniscal (24.9 ± 4.3 N) versus adipose (1.1 ± 0.2N) or muscle tissue (0.8 [interquartile range 0.6-1.1] N) using a 1 mL syringe (p < 0.01), while less force was required when using a microsyringe (0.5 [interquartile range 0.4-0.5] N) versus 1 mL syringe (p < 0.0001). When different injection volumes were compared, the indicators were significantly higher after a 10-μL versus 5-μL injection (p < 0.05). When the same amount of Fast Green FCF solution was injected, the indicators were larger in the degenerative human versus healthy porcine menisci. The injection of rIL-1β promoted inflammatory factor and matrix proteinase transcription in meniscal cells. In contrast, the injection of dexamethasone into meniscal tissue cultured in rIL-1β-containing medium suppressed this transcription. The injection of papain resulted in decreased Safranin O staining and a changed picrosirius red staining pattern. Conclusion: These results provide new insights that may serve as a basis for the more useful clinical application of intrameniscal injections. Level of evidence: V, Mechanism-based reasoning/Lab Studies.

INTRODUCTION:The meniscus is an essential structure of the knee joint, performing functions such as load transmission, shock absorption, joint stability, and joint lubrication. The deterioration of meniscal function due to trauma or degenerative changes causes meniscal-related symptoms and leads to cartilage damage and osteoarthritis. Current treatments target not the meniscus itself, but the entire knee joint or intra-articular tissues, and non-surgical treatments that directly access the meniscal tissues are not widely used. This study aimed to evaluate the effects of the intrameniscal injection technique on meniscal tissue and cells. METHODS:Four healthy porcine menisci and 10 human menisci from patients after total knee arthroplasty were injected with different solutions to investigate the required injection force, intrameniscal distribution of the injected solution, and biological effects on the meniscal cells. The initial force exerted by the syringe piston was measured by a pressure gauge. After the injection of Fast Green FCF solution, the distribution was observed, measured, and analyzed in 3 indicators: Width, Stained Area, and Calculated Volume. Other meniscal tissues were injected with recombinant interleukin-1 beta (rIL-1β), dexamethasone or papain, cultured and harvested for qRT-PCR or histology analysis. RESULTS:Statistically significantly greater force was required for the intrameniscal (24.9 ± 4.3 N) versus adipose (1.1 ± 0.2N) or muscle tissue (0.8 [interquartile range 0.6-1.1] N) using a 1 mL syringe (p < 0.01), while less force was required when using a microsyringe (0.5 [interquartile range 0.4-0.5] N) versus 1 mL syringe (p < 0.0001). When different injection volumes were compared, the indicators were significantly higher after a 10-μL versus 5-μL injection (p < 0.05). When the same amount of Fast Green FCF solution was injected, the indicators were larger in the degenerative human versus healthy porcine menisci. The injection of rIL-1β promoted inflammatory factor and matrix proteinase transcription in meniscal cells. In contrast, the injection of dexamethasone into meniscal tissue cultured in rIL-1β-containing medium suppressed this transcription. The injection of papain resulted in decreased Safranin O staining and a changed picrosirius red staining pattern. CONCLUSION:These results provide new insights that may serve as a basis for the more useful clinical application of intrameniscal injections. LEVEL OF EVIDENCE:V, Mechanism-based reasoning/Lab Studies.

Selecting the optimal biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) for individual patients with rheumatoid arthritis (RA) remains an unresolved clinical challenge. We developed and externally validated a causal inference framework that integrates a double machine learning-based causal forest model with guideline-derived safety constraints for b/tsDMARD category selection. Using multi-centre registry data (4,885 treatment courses from eight Japanese rheumatology facilities), the model was trained on six facilities (n = 2,425) and externally validated on two independent facilities (n = 2,460). The framework first estimates individualised treatment effects via the causal forest with double machine learning, then applies a guideline-based safety rule that exclude JAK inhibitors for patients with multiple cardiovascular risk factors before finalising recommendations. Patients receiving treatments concordant with AI recommendations achieved significantly higher clinical disease activity index response rates than those with discordant treatments: crude analysis 33.6% vs 27.2% (absolute risk difference [ARD] = 6.4%, P = 0.002; number needed to treat = 16), propensity score-matched analysis 33.6% vs 28.2% (ARD = 5.5%, P = 0.037), and inverse probability of treatment weighting 31.6% vs 27.3% (ARD = 4.3%, P = 0.044). The system identified significant heterogeneity in conditional average treatment effects (group average treatment effects Q4–Q1: Z = 4.64, P < 0.001) and 12 clinically interpretable effect modifiers confirmed by two independent analytical methods. Treatment line-stratified analysis revealed that second-line patients derived the greatest benefit (ARD = 16.0%, number needed to treat = 6.3, P = 0.0002). These findings demonstrate that an AI framework combining data-driven causal inference with guideline-derived safety guardrails can identify patients who benefit from personalised b/tsDMARD selection in RA.

In Japan, pharmacological treatment for rheumatoid arthritis (RA), including biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi), is provided by both orthopaedic surgeons and rheumatologists. However, differences in patient characteristics, treatment selection, and outcomes between these two clinical settings have not been fully elucidated. This study aimed to compare these factors using real-world data. Using the ANSWER cohort, we identified 7268 RA treatment courses initiating bDMARDs or JAKi between August 2002 and May 2023. Patients were classified into orthopaedic surgeon–managed and rheumatologist-managed groups. Patient characteristics and treatment patterns were compared. Treatment retention due to ineffectiveness and adverse events was assessed using Cox proportional hazards models to estimate hazard ratios (HRs) adjusted for potential confounders. Compared with the rheumatologist-managed group, patients managed by orthopaedic surgeons had longer disease duration, higher seropositivity, greater functional impairment, although lower comorbidity prevalence such as hypertension, dyslipidemia, and diabetes mellitus. Methotrexate, tumor necrosis factor inhibitors, JAKi, and intra-articular injections were used more frequently, whereas oral glucocorticoids were used less frequently. After adjustment, treatment retention due to ineffectiveness was comparable between groups (HR 0.98, 95

Neglected congenital clubfoot in adults is difficult to manage. Multi-joint arthrodesis is often required but is invasive and associated with complications. We report an adult case treated with ankle arthrodesis and midfoot derotational osteotomy. A 59-year-old man with untreated idiopathic clubfoot since birth presented with severe hindfoot varus and rigid midfoot inversion, leading to wheelchair dependence. Imaging showed correctable hindfoot deformities but rigid midfoot inversion with talonavicular subluxation. Surgery consisted of Achilles tendon lengthening, ankle and subtalar arthrodesis with a retrograde intramedullary nail, and midfoot derotational osteotomy, resulting plantigrade. Bony union was confirmed at one year. At 3 years, plantigrade alignment remained without recurrence. Callosities resolved, and the patient regained pain-free walking. Clinical scores improved: Japanese Society for Surgery of the Foot ankle/hindfoot (4.0 to 66.0), Japanese Society for Surgery of the Foot midfoot (0.0 to 73.0), self-administered foot evaluation questionnaire (89.2 to 366.0). This is the first report of midfoot derotational osteotomy for neglected congenital clubfoot, offering a less invasive option for selected adults.

Abstract Objectives To compare early changes in rheumatoid factor (RF) across classes of biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and assess whether early RF decline was associated with 12-month clinical remission in rheumatoid arthritis (RA). Methods We retrospectively analysed 1,423 newly initiated b/tsDMARD treatment courses from the multicentre ANSWER cohort that continued for ≥12 months and had RF measured at baseline and 3 months. Early RF decline was defined as a ≥ 20% reduction at 3 months. Multivariable regression assessed factors associated with RF change and 12-month Clinical Disease Activity Index (CDAI) remission. Twelve-month remission rates were also compared across four categories of RF reduction. Results RF reduction differed across classes, with Janus kinase inhibitors (JAKi) showing the greatest decline. Compared with tumour necrosis factor inhibitors (TNFi), JAKi were associated with a greater RF reduction (β = −14.50, 95% CI − 20.04 to − 8.97; P < 0.001). The direction was similar in multiple sensitivity analyses and remained significant in propensity score-matched analyses. Early RF decline was independently associated with 12-month CDAI remission (adjusted OR 1.39, 95% CI: 1.04–1.88; P = 0.029). A significant overall trend towards higher 12-month remission rates was observed across categories of greater RF reduction (P for trend = 0.004). Conclusions Early RF decline differed across b/tsDMARD classes and was associated with 12-month remission. Longitudinal RF dynamics may provide clinically useful prognostic information in RA.

Selecting the optimal biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) for patients with rheumatoid arthritis remains challenging. We developed and externally validated a causal inference framework combining double machine learning-based causal forests with guideline-derived safety constraints. Using multi-centre registry data from eight Japanese rheumatology facilities (4885 treatment courses), the model was trained on six facilities (n = 2425) and externally validated on two facilities (n = 2460). The framework estimates individualised treatment effects and applies a guideline-based safety rule that excludes Janus kinase inhibitors for patients with multiple cardiovascular risk factors. Patients receiving AI-concordant treatments had higher response rates than those receiving discordant treatments: 33.6% vs 27.2% in crude analysis (absolute risk difference [ARD] = 6.4%, P = 0.002; number needed to treat [NNT] = 16), with consistent effects after propensity score matching (ARD = 5.5%, P = 0.037) and inverse probability of treatment weighting (ARD = 4.3%, P = 0.044). The model identified treatment-effect heterogeneity (group average treatment effects Q4–Q1: Z = 4.64, P < 0.001) and 12 clinically interpretable effect modifiers confirmed by two analytical methods. Benefit was greatest in second-line patients (ARD = 16.0%, NNT = 6.3, P = 0.0002), supporting personalised b/tsDMARD selection.

Exercise therapy (ET) is a valuable adjunctive treatment for rheumatoid arthritis (RA). We hypothesized that ET supports maintenance of remission or low disease activity (LDA) during targeted drug therapy (TT) tapering. This pilot randomized controlled trial evaluated the feasibility, safety, and preliminary effects of individualized ET in RA patients undergoing TT tapering. Thirty-two RA patients initiating TT tapering were randomized to receive personalized ET plus usual care (intervention group, n = 16) or usual care alone (control group, n = 16) for 16 weeks. The primary exploratory outcome was the proportion of patients maintaining remission or LDA (DAS28-ESR < 3.2) by week 16 without TT re-escalation. Secondary outcomes included DAS28-ESR and its component measurements at weeks 8 and 16, health-related quality of life at week 16 (SF-12), physical activity (IPAQ), and daily step count. Safety and adherence were also assessed. All participants in the intervention group completed the 16-week ET program with high adherence. Remission or LDA was maintained in 75.0

Surgical treatment for forefoot deformities in patients with rheumatoid arthritis has recently shifted toward joint-preserving procedures for all toes. In contrast, resection arthroplasty was previously more commonly performed for the lesser toes. Advances in drug therapy have improved life expectancy, resulting in an increased number of long-term survivors who had previously underwent resection arthroplasty. With increased activity levels, the recurrence of plantar callosities in the forefoot has become more frequent, often leading to gait disturbances. In general, revision surgery for such cases often involves additional bone resection; however, this approach may result in further shortening of the metatarsals and increase the risk of further recurrence. Therefore, we applied a metatarsal-shortening offset osteotomy, which we typically perform as a primary procedure, as a salvage procedure to reduce the risk of recurrence. We report three cases treated using this strategy. In all cases, the second to fifth metatarsal heads had been resected, but the resection stumps were covered with pseudo-cartilaginous tissue. This allowed a metatarsal-shortening offset osteotomy to be performed as a procedure similar to that used in primary surgery, achieving the planned correction. Consequently, both radiographic and clinical improvements were observed. These findings suggest that a metatarsal-shortening offset osteotomy may be a possible salvage option after primary resection arthroplasty for forefoot deformities in patients with rheumatoid arthritis.

OBJECTIVES:We evaluated real-world disease activity, treatment patterns and pregnancy outcomes in women with rheumatoid arthritis (RA) utilizing a multicentre Japanese cohort. Feasibility and impact of a treat-to-target (T2T) approach during pregnancy were also examined. METHODS:A retrospective observational study analysed 118 pregnancies in patients with RA from the multicentre ANSWER cohort (2013-2023) across eight Japanese academic institutions. Clinical characteristics, treatment regimens and RA Disease Activity Scores of 28 joints based on C-reactive protein (DAS28-CRP) were assessed at preconception, during each trimester and postpartum. Pregnancy and neonatal outcomes were analysed. RESULTS:Of 118 pregnancies, 92.8% achieved full-term deliveries (median birthweight: 2949 g). Remission or low disease activity was maintained in ∼85% of patients throughout pregnancy, with increased postpartum disease activity. Patients who continued biologic disease-modifying antirheumatic drugs (bDMARDs) during pregnancy (n = 35) exhibited significantly lower DAS28-CRP scores during the second and third trimesters compared with those who discontinued (n = 24) (P = 0.007 and P = 0.0002, respectively). Etanercept or certolizumab pegol use was associated with favourable disease control. Tocilizumab (n = 6) or abatacept (n = 2) was not associated with adverse maternal or neonatal outcomes. Glucocorticoid use was associated with increased disease activity. Salazosulfapyridine use correlated with increased birth weight (P = 0.003) and gestational age (P = 0.051). CONCLUSION:T2T management, including selective continuation of bDMARDs, was associated with favourable maternal disease control and reassuring pregnancy outcomes. Although the absence of long-term follow-up is a limitation, these findings provide real-world evidence supporting this approach. Larger prospective studies are required to confirm maternal and neonatal safety beyond the early postpartum.

Muscle hematomas can exacerbate inflammation, delay healing, and reduce function after muscle injury. This study examined whether early hematoma removal promoted recovery in a rat model of tibialis anterior muscle laceration. Hematomas were surgically removed 6 h after injury and compared with untreated animals. Histological analysis revealed that the hematoma removal group had a significantly reduced hematoma size 24 h after injury and a significantly reduced abnormal tissue area on days 3 and 14. Furthermore, the hematoma removal group demonstrated better muscle strength recovery at 3, 14, and 28 days post-injury. Gene expression analysis of the injured muscle tissue revealed that the expression levels of several genes related to inflammation and inflammatory pain (IL-6, IL-10, IL-1β, TNF-α, IL-1Ra, COX-1, COX-2, NGF) and macrophage marker molecules (CD68, ADGRE1, CD206, Arg1) during the acute phase were significantly lower in the hematoma removal group compared to the control group. No significant differences were observed in the transcription levels of the genes related to myogenic differentiation. In summary, early surgical hematoma removal in a rat laceration model reduced inflammation and abnormal tissue volume and promoted muscle strength recovery. This study provides new evidence suggesting that early hematoma removal after skeletal muscle injury is beneficial.

Baseline serum PINP was significantly and independently associated with achieving a ≥ 8

A patient with rheumatoid arthritis and a flexible rocker-bottom foot deformity underwent surgery, including a flexor digitorum longus transfer, a spring ligament reconstruction, and a lateral column lengthening using calcaneocuboid distraction arthrodesis, while preserving the talonavicular and subtalar joints. Correction was achieved with the restoration of the medial longitudinal arch, and clinical outcome scores had improved at the final follow-up (1 year postoperatively). This case suggests that, even in patients with inflammatory joint diseases presenting with a rocker-bottom foot deformity, reconstruction preserving the talonavicular and subtalar joints may be considered as a treatment option when disease activity is adequately controlled with pharmacotherapy and the talonavicular and subtalar joints are not destroyed, as in the present case.

Objectives This study aimed to compare 24-month drug retention between standard-dose and reduced-dose Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) and to examine whether poor prognostic factor (PPF) burden and renal function modify treatment persistence, with primary inference restricted to patients with preserved renal function, in whom reduced dosing reflects discretionary clinical decision-making. Methods We conducted a multicentre observational study using a Japanese real-world registry of patients with RA who initiated JAKi between 2013 and 2025. Patients were classified according to their initial JAKi dosing strategy. Primary analyses were performed in patients with preserved renal function. Propensity score matching was used to adjust for confounding by indication. Drug retention over 24 months was assessed using Kaplan-Meier analyses and Cox proportional hazards models, with prespecified stratification by PPF burden (0-2 vs 3-4). Supportive analyses were conducted in patients with reduced renal function. Results Among 1135 patients, 24-month drug retention was comparable between standard-dose and reduced-dose JAKi in the matched cohort with preserved renal function. Disease activity improved similarly in both groups, and glucocorticoid use remained low without compensatory escalation. Reduced dosing performed comparably in patients with low PPF burden, whereas standard-dose initiation showed more favourable persistence in patients with multiple PPFs. In patients with reduced renal function, standard dosing was associated with higher drug retention. Conclusions In patients with preserved renal function, reduced-dose JAKi initiation was associated with 24-month treatment persistence comparable with standard dosing. Findings in PPF-stratified analyses and in patients with reduced renal function should be interpreted cautiously and warrant further investigation.

OBJECTIVE:This study aimed to compare drug retention rates according to the baseline neutrophil-to-lymphocyte ratio (NLR) in patients with RA initiating biologic/targeted synthetic DMARDs (b/tsDMARDs). METHODS:Data were obtained from 774 treatment courses with moderate to high disease activity at the initiation of b/tsDMARD therapy from the Kansai Multicentre ANSWER cohort. Patients were categorized into NLRlow group and NLRhigh group based on the median NLR value of 3.30. A multivariate Cox proportional hazards model, adjusted for potential confounders, was used to estimate hazard ratios (HRs) for drug retention over 2 years. RESULTS:Patients in the NLRhigh group exhibited significantly higher baseline Clinical Disease Activity Index (CDAI) scores (P = 0.004) and more frequent glucocorticoid use (P < 0.001) than those in the NLRlow group. In the NLRlow group, drug retention rates did not significantly differ among tumour necrosis factor inhibitors (TNFi), anti-IL-6 receptor antibodies (aIL-6R), cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4-Ig) and Janus kinase inhibitors (JAKi). In contrast, within the NLRhigh group, treatment with aIL-6R and JAKi was associated with significantly higher retention rates compared with TNFi (HR = 0.53, 95% CI: 0.32-0.88; HR = 0.36, 95% CI: 0.20-0.64, respectively). At 12 months, CDAI scores did not significantly differ among the four treatment groups in either NLR group. CONCLUSION:In patients with elevated baseline NLR values, aIL-6R and JAKi may offer superior drug retention compared with TNFi when initiating b/tsDMARD therapy.