Prognosis and prognostic factors of lung cancer complications in patients with rheumatoid arthritis.

AIM: To clarify the prognosis and prognostic factors for lung cancer in patients with rheumatoid arthritis (RA). METHODS: In this retrospective longitudinal study, we investigated the medical records of patients with RA among 1422 patients diagnosed with lung cancer and registered in a hospital-based cancer registry between January 2013 and May 2022. The Kaplan-Meier method and Cox proportional hazards model were used to analyze survival and identify predictive factors. RESULTS: Of 26 patients with RA complicated with lung cancer (median age, 69 years), the 2-year overall survival rates for stages I-II were 90%-100%, and those for stages III-IV were 20%, respectively. Positivity of anti-citrullinated protein/peptide antibody, smoking history, interstitial lung disease, poorly controlled RA, stage III and IV lung cancer, histological types other than adenocarcinoma and squamous cell carcinoma, and RF ≧ 50 IU/mL were associated with increased mortality. After the surgical resection of stage I and II lung cancer, 5 of the 16 patients experienced cancer recurrence after resumption of RA treatment, and the histology of the recurrent cancers was mostly squamous cell carcinoma. CONCLUSIONS: Early detection of lung cancer is needed, especially in patients with RA who have a history of smoking, seropositivity, or interstitial lung disease. Even after surgical resection, it should be noted that squamous cell carcinoma is prone to recurrence.

GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.

Here we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population. Further analysis shows that rs10917688 is marked with H3K4me1 in primary B cells. A meta-analysis with a European GWAS detects 30 additional significant loci. Polygenic risk scores constructed with the effect sizes of the meta-analysis suggest the potential portability of genetic associations beyond populations. Prioritizing the top 5% of SNPs of IRF8 binding sites in B cells improves the fitting of the polygenic risk scores, underscoring the roles of B cells and IRF8 in the development of systemic sclerosis. The results also suggest that systemic sclerosis shares a common genetic architecture across populations.

Computed tomography for malignancy screening in patients with rheumatoid arthritis before initiation of disease modifying antirheumatic drug.

OBJECTIVES: This study aimed to clarify the usefulness of screening for malignancies using CT before the initiation of biologic and targeted synthetic DMARDs (b/tsDMARDs) in patients with active RA. METHODS: We examined 2192 patients with RA who underwent plain CT scans prior to the initiation of b/tsDMARDs. The sensitivity for detecting malignancy was measured and compared with that of regular screening (physical examination and X-ray). We then evaluated the clinical characteristics, prognosis and treatment of patients with RA with concomitant malignancies. Additionally, we determined the incidence rate of malignancy in patients with RA who were initiated on b/tsDMARDs after CT screening. RESULTS: Of the 2192 patients, 33 (1.5%) were diagnosed with malignancy after CT screening. Whereas regular screening detected only seven malignancies, CT screening further detected 26 (including 19 at the early stage). On the other hand, 86% of the malignancies detectable by regular screening were at an advanced stage. Patients diagnosed with early-stage malignancies received RA treatments that included b/tsDMARDs after curative resection; 80% of these patients achieved low disease activity after 1 year. This rate was comparable to the patients without malignancy detection after screening (70%). The 5 year incidence of malignancy after the initiation of b/tsDMARDs after CT screening was lower than that of the RA cohort without CT screening (standardized incidence ratio: 0.35). CONCLUSION: Screening in patients with RA using CT before the initiation of b/tsDMARDs allows for the early detection and treatment of malignancy, resulting in safer and more stable b/tsDMARD treatments.

Abatacept ameliorates both glandular and extraglandular involvements in patients with Sjögren's syndrome associated with rheumatoid arthritis: Findings from an open-label, multicentre, 1-year, prospective study: The ROSE (Rheumatoid Arthritis with Orencia Trial Toward Sjögren's Syndrome Endocrinopathy) and ROSE II trials.

OBJECTIVE: To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). MATERIALS AND METHODS: We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed. RESULTS: 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients. CONCLUSION: Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.

Illustrations of rheumatoid arthritis symptoms to promote communications between patients and physicians.

OBJECTIVES: To develop an illustrative tool presenting visualized rheumatoid arthritis (RA) symptoms using pictures to promote a better understanding between patients and physicians. METHODS: The tool named 'Okomarigoto Sheet' was developed through an Internet survey of patients with RA and certified rheumatologists by repeated in-person interviews. RESULTS: An Internet survey on the reality of communication between patients with RA and physicians in 200 patients and 200 certified rheumatologists revealed various local and systemic symptoms of RA and difficulties in sharing those symptoms between patients and physicians during a short consultation. Interviews from patients and certified rheumatologists suggested that illustrations of symptoms would be helpful for better communication between them; therefore, an illustrative tool presenting visualized RA symptoms was drafted. The draft illustrations were refined through multiple rounds of interviews with the patients. The final version of the tool was discussed and evaluated at a joint meeting of patients and rheumatologists. CONCLUSIONS: A picture sheet presenting RA symptoms was developed. Future prospective studies should evaluate the usefulness of the sheet in clinical practice to promote better communication between patients and physicians.

Role of DNA dioxygenase Ten-Eleven translocation 3 (TET3) in rheumatoid arthritis progression.

BACKGROUND: Rheumatoid arthritis (RA) patients present with abnormal methylation patterns in their fibroblast-like synoviocytes (FLS). Given that DNA demethylation is critical for producing DNA methylation patterns, we hypothesized that DNA demethylation may facilitate RA progression. Therefore, we designed this study to examine the role of DNA dioxygenase family, Ten-Eleven translocation (TET1/2/3), in the pathological process of RA. METHODS: Synovial tissues and FLS were obtained from patients with RA and Osteoarthritis. K/BxN serum-induced arthritis was induced in Wild-type (WT) and TET3 heterozygous-deficient (TET3+/-) C57BL/6 mice. RESULTS: We found that both TET3 and 5-hydroxymethylcytosine (5hmC) were upregulated in synovitis tissues from RA patients and confirmed this upregulation in the cultured FLS derived from synovitis tissues. Tumor necrosis factor α (TNFα) upregulated TET3 and 5hmC levels in cultured FLS, and the stimulated FLS exhibited high cell mobility with increased transcription of cellular migration-related factors such as C-X-C motif chemokine ligand 8 (CXCL8) and C-C motif chemokine ligand 2 (CCL2) in a TET3-dependent manner. In addition, TET3 haploinsufficiency lowered RA progression in a mouse model of serum-induced arthritis. CONCLUSIONS: Based on these findings, we can assume that TET3-mediated DNA demethylation acts as an epigenetic regulator of RA progression.

Remission of Granulomatosis with Polyangiitis Only After Resection of a Pulmonary Nodule.

Granulomatosis with polyangiitis (GPA) is characterized by necrotizing granulomatous lesions and is classified as ANCA-associated vasculitis (AAV). We herein report a case of GPA that was remitted by resection of a pulmonary lesion without immunosuppressive therapy. We detected activated neutrophils and neutrophil extracellular traps (NET) formation in resected lung tissue by immunofluorescence. Activated neutrophils and NETs might be involved in the pathophysiology of AAV and induce the vicious cycle of ANCAs and NETs. In cases of GPA with no other severe lesions, the reevaluation of the disease activity after diagnostic resection is crucial for considering the need for immunosuppressive therapy.

TRAPS mutations in Tnfrsf1a decrease the responsiveness to TNFα via reduced cell surface expression of TNFR1.

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autoinflammatory periodic fever syndrome associated with heterozygous mutations in TNFRSF1A, which encodes TNF receptor type I (TNFR1). Although possible proinflammatory mechanisms have been proposed, most previous studies were performed using in vitro overexpression models, which could lead to undesirable inflammatory responses due to artificial overexpression. It is crucial to reproduce heterozygous mutations at physiological expression levels; however, such studies remain limited. In this study, we generated TRAPS mutant mice and analyzed their phenotypes. Three Tnfrsf1a mutant strains were generated by introducing T79M, G87V, or T90I mutation. T79M is a known mutation responsible for TRAPS, whereas G87V is a TRAPS mutation that we have reported, and T90I is a variant of unknown significance. Using these murine models, we investigated whether TRAPS mutations could affect the inflammatory responses in vivo and in vitro. We found that none of the mutant mice exhibited detectable inflammatory phenotypes under standard housing conditions for 1 year. Interestingly, TRAPS mutant (T79M and G87V) mice had reduced mortality rates after the administration of lipopolysaccharide (LPS) and D-galactosamine, which induce TNFα-dependent lethal hepatitis. Moreover, TRAPS mutations strongly suppressed the development of TNFα-mediated arthritis when crossed with human TNFα transgenic mice. In in vitro primary bone marrow-derived macrophage cultures, the T79M and G87V mutations attenuated the inflammatory responses to TNFα compared with the wild-type, whereas these mutations did not alter the responsiveness of these cells to LPS. The T90I mutant macrophages behaved similarly to wild type in response to LPS and TNFα. The TNFR1 levels were increased in whole-cell lysates of TRAPS mutant macrophages, whereas the cell surface expression of TNFR1 was significantly decreased in TRAPS mutant macrophages. Taken together, TRAPS mutations did not augment the inflammatory responses to TNFα and LPS; instead, they suppressed the response to TNFα via decreased cell surface expression of TNFR1. The stimulation of lymphotoxin-α, adenosine triphosphate, and norepinephrine in primary macrophages or various stimuli in murine splenocytes did not induce detectable inflammatory responses. In conclusion, TRAPS mutations suppressed responsiveness to TNFα, and TRAPS-associated inflammation is likely induced by unconfirmed disease-specific proinflammatory factors.

Allogeneic stem cell transplantation for trisomy 8-positive myelodysplastic syndrome or myelodysplastic/myeloproliferative disease with refractory Behçet's disease: Case report and the review of literature.

We had two cases of trisomy 8-positive myelodysplastic syndrome (MDS) with incomplete Behçet's disease (BD) in which the remissions of both diseases were maintained by allogeneic stem cell transplantation (allo-SCT). Among MDS with BD patients, sometimes it is difficult to control the symptoms of BD with standard therapies such as corticosteroids and tumor necrosis factor (TNF) inhibitors. Although there should be careful consideration regarding indications for transplantation, our two cases, in which refractory BD was completely controlled by allo-SCT, suggest that allo-SCT can be one of the treatment options for higher-risk MDS with BD patients.

Nailfold microvascular abnormalities are associated with a higher prevalence of pulmonary arterial hypertension in patients with MCTD.

OBJECTIVE: MCTD manifests with microvasculopathy and overlapping clinical features of SLE, SSc and idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the clinical significance of microvasculopathy in patients with MCTD using nailfold videocapillaroscopy (NVC). METHODS: Fifty patients with newly diagnosed and untreated MCTD were enrolled in this multicentre, prospective and observational study. Clinical features and NVC findings were assessed at baseline and after 1 year post-intervention, along with disease controls [SLE (n = 40), SSc (n = 70) and IIM (n = 50)]. RESULTS: All MCTD patients presented Raynaud's phenomenon and were positive for anti-U1 RNP antibodies, and 22.0% (11/50) had pulmonary arterial hypertension (PAH). The prevalence of NVC scleroderma patterns in MCTD was 38.0%, which was lower than SSc (88.6%) but higher than SLE (10.0%). In addition, when we divided MCTD patients into two groups by presence or absence of NVC scleroderma patterns, we found a higher prevalence of PAH in patients with NVC scleroderma patterns. Namely, NVC scleroderma patterns were observed in all MCTD patients with PAH, and in 21.0% of those without PAH. After intensive immunosuppressive therapy, NVC scleroderma patterns disappeared in half of the MCTD patients but were not changed in SSc patients. CONCLUSIONS: MCTD differed from SLE, SSc and IIM in terms of the prevalence and responsiveness of NVC scleroderma patterns to immunosuppressive therapy. Detection of nailfold microvascular abnormalities in MCTD could contribute to predicting PAH and help us to understand further aspects of the pathogenesis of MCTD.

A case of mixed connective tissue disease complicated by pulmonary hypertension and ascites after addition of pulmonary vasodilators.

We present the case of a 54-year-old woman with a long history of pulmonary hypertension associated with mixed connective tissue disease. She was being treated with pulmonary vasodilators, including epoprostenol and bosetan, but her mean pulmonary arterial pressure (mPAP) gradually worsened. Although her mPAP began to improve with adding sildenafil, ascites occurred. Discontinuing newly initiated drugs and starting diuretics improved her ascites. This suggested that an intensification of the treatment with vasodilators might have led to ascites (on a background of a probable arteriovenous shunt formation) in this patient with a long history of pulmonary hypertension.

Short-Term Prognostic Factors in Hospitalized Herpes Zoster Patients and Its Associated Cerebro-Cardiovascular Events: A Nationwide Retrospective Cohort in Japan.

Background: Short-term mortality and incidence of cerebrovascular and cardiovascular events (C-CVE) during hospitalization of patients with severe herpes zoster (HZ) have not been sufficiently investigated. We aimed to investigate short-term prognosis and incidence of C-CVE associated with HZ in hospitalized patients. Methods: This retrospective cohort study from April 2016 to March 2018 included HZ inpatient cases selected from the Diagnosis Procedure Combination database-a Japanese nationwide inpatient database. HZ and C-CVE were diagnosed based on the 10th revision of the International Classification of Diseases and Injuries codes. The definition of primary exposure was that treatments were initiated within 7 days of admission, and antivirals were administered for ≥7 days. Main Outcomes were in-hospital deaths and C-CVE onset after hospitalization. Results: Among 16,811,501 in-hospital cases registered from 1,208 hospitals, 29,054 cases with HZ were enrolled. The median age was 71.0 years, 15,202 cases (52.3%) were female, and the HZ types were the central nervous system (n=9,034), disseminated (n=3,051), and ophthalmicus (n=1,069) types. There were 301 (1.0%) in-hospital deaths and 385 (1.3%) post-hospitalization onset of C-CVE. The 30-day in-hospital survival rates with or without underlying disease were 96.8% and 98.5%, respectively. Age ≥75 years (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.55-3.05), liver cirrhosis or hepatic failure (HR, 5.93; 95% CI, 2.16-16.27), chronic kidney disease (HR, 1.82; 95% CI, 1.24-2.68), heart failure (HR, 1.65; 95% CI, 1.22-2.24), and old cerebrovascular events (HR, 1.92; 95% CI, 1.10-3.34) were associated with poor short-term prognosis. Age ≥75 years (odds ratio [OR], 1.70; 95% CI, 1.29-2.24), diabetes (OR, 1.50; 95% CI, 1.19-1.89), dyslipidemia (OR, 1.95; 95% CI, 1.51-2.51), hyperuricemia (OR, 1.63; 95% CI, 1.18-2.27), hypertension (OR, 1.76; 95% CI, 1.40-2.20), heart failure (OR, 1.84; 95% CI, 1.32-2.55), and glucocorticoid administration (OR, 1.59; 95% CI, 1.25-2.01) were associated with increased risks for in-hospital C-CVE onset. Conclusions: The underlying diseases that could influence the short-term mortality of severe HZ were identified. Glucocorticoid is a possible risk factor for the in-hospital onset of C-CVE after severe HZ development.

IL-17A promotes vascular calcification in an ex vivo murine aorta culture.

BACKGROUND: Vascular calcification is characterized by mineral deposition in the vasculature, which is triggered by chronic systemic inflammation, including psoriasis. Psoriasis is an IL-17A-mediated inflammatory skin disease that is associated with exacerbated vascular calcification and high cardiovascular mortality. Although previous studies have shown that IL-17A induces vascular dysfunction in murine psoriasis models, it has not been clarified whether IL-17A induces vascular calcification. In this study, we investigated the potential vascular calcification-inducing effect of IL-17A in an ex vivo culture system. METHODS: Thoracic and abdominal aortas from mice were cultured in a medium supplemented with inorganic phosphate and were treated with inflammatory cytokines (IL-1ß, TNF-α, IL-6, and IL-17A). Vascular calcification was determined using micro-computed tomography (CT) and histological analyses. RESULTS: IL-1ß, TNF-α, and IL-6 did not significantly promote vascular calcification, whereas IL-17A significantly accelerated vascular calcification of the aorta, as indicated by the increased mineralized volume based on micro-CT analysis. Micro-CT and histological analyses also revealed that the promoting effect of IL-17A on vascular calcification was concentration dependent. CONCLUSIONS: IL-17A significantly promoted vascular calcification in ex vivo cultured aortas, which suggests that this mechanism is involved in the increased risk of cardiovascular events in IL-17A-mediated inflammatory diseases.

Selection of treatment regimens based on shared decision-making in patients with rheumatoid arthritis on remission in the FREE-J study.

OBJECTIVE: To compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission. METHODS: At period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at <2.6 were divided into five groups based on shared patient/physician decision-making; continuation, dose reduction and discontinuation of MTX or bDMARDs. At end of year 1, patients who achieved DAS28(ESR) <3.2 were allowed to enrol in period 2 for treatment using the de-escalation regimens for another year. The primary and secondary endpoints were the proportion of patients with DAS28(ESR) <2.6 at year 1 and 2, respectively. RESULTS: Based on shared decision-making, 81.4% elected de-escalation of treatment and 48.4% selected de-escalation of MTX. At end of period 1, similar proportions of patients maintained DAS28(ESR) <2.6 (continuation, 85.2%; MTX dose reduction, 79.0%; MTX-discontinuation, 80.0%; bDMARD dose reduction, 73.9%), although the rate was significantly different between the continuation and bDMARD-discontinuation. At end of period 2, similar proportions of patients of the MTX groups maintained DAS28(ESR) <2.6 (continuation or de-escalation), but the rates were significantly lower in the bDMARD-discontinuation group. However, half of the latter group satisfactorily discontinued bDMARDs. Adverse events were numerically lower in MTX and bDMARD-de-escalation groups during period 1 and 2, compared with the continuation group. CONCLUSIONS: After achieving sustained remission by combination treatment of MTX/bDMARDs, disease control was achieved comparably by continuation, dose reduction or discontinuation of MTX and dose reduction of bDMARDs at end of year 1. Subsequent de-escalation of MTX had no impacts on disease control but decreased adverse events in year 2.

A case of simultaneous onset of highly active systemic lupus erythematosus and IgG4-related renal disease.

The patient was a 73-year-old woman who had hair loss, purpura, and numbness of the soles for past 1 year. Three months prior, she was diagnosed with interstitial lung disease (ILD) and was admitted to our department. She was diagnosed with systemic lupus erythematosus (SLE) based on positive antinuclear antibodies 1280× (speckled type), hair loss, low white blood cell count, positive anti-cardiolipin and anti-ds-DNA antibodies, and lupus retinopathy. In addition, the patient was also diagnosed with immunoglobulin G (IgG)4-related disease (IgG4RD) based on high serum IgG4 levels, ILD, urine occult blood, protein, and cast, and renal histological findings showed endocapillary proliferative glomerulonephritis, increased IgG4 positive plasma cells, and characteristic storiform fibrosis. High-dose glucocorticoid therapy, hydroxychloroquine, and belimumab were administered, which improved the SLE symptoms of lupus retinopathy and peripheral neuropathy, as well as the IgG4RD symptoms of ILD and urinary findings. Herein, we report a rare case of simultaneous onset of IgG4-related nephropathy with active glomerular lesions and SLE, in which renal histology, including fluorescent antibodies, was crucial for diagnosis.

Difficult-to-treat rheumatoid arthritis with respect to responsiveness to biologic/targeted synthetic DMARDs: a retrospective cohort study from the FIRST registry.

OBJECTIVES: Difficult-to-treat rheumatoid arthritis (dt-RA) is an emerging concept defined as persistency of signs and/or symptoms despite prior treatment. However, whether this refractoriness affects effectiveness and tolerance to next treatment is not fully understood. This study aimed to find cut-off values for a definition of dt-RA with respect to responsiveness to newly used biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). METHODS: A retrospective cohort study was conducted using the FIRST registry. An inadequate response to current b/tsDMARDs was defined as clinical disease activity index >10 at week 22 or termination of treatment within 22 weeks due to insufficient efficacy. Cut-off values were defined according to the number of past failures to DMARDs and current dose of glucocorticoid. Responsiveness to newly used b/tsDMARDs were compared with respect to above versus below cut-off values. RESULTS: Failures to ≥2 conventional synthetic DMARDs (csDMARDs) and ≥4 b/tsDMARDs as well as ≥3mg/day of glucocorticoid were independent cut-off values associated with poor responsiveness to newly used b/tsDMARD treatment. Concomitant use of glucocorticoid was significantly correlated with an increased hazard of infection. Failures to ≥2 csDMARDs was associated with less improvement in inflammatory symptoms, while that to ≥4 b/tsDMARDs was associated with less improvement in health assessment questionnaire and global health as well. CONCLUSIONS: We propose cut-off values of ≥2 failures to csDMARDs and/or ≥4 b/tsDMARDs as a definition of dt-RA with respect to responsiveness to use of b/tsDMARDs.

Characteristics of rheumatoid arthritis with immunodeficiency-associated lymphoproliferative disorders to regress spontaneously by the withdrawal of methotrexate and their clinical course: A retrospective, multicenter, case-control study.

OBJECTIVE: To investigate clinical characteristics and time course of lymphoproliferative disorders (LPDs) in rheumatoid arthritis (RA) patients after methotrexate (MTX) discontinuation, in those who achieved spontaneous regression (SR). METHODS: We retrospectively reviewed clinical data from RA patients with LPDs obtained from eight institutions between 2000 and 2017 and compared clinical and pathological findings between SR and non-SR groups. RESULTS: Among 232 RA patients with LPDs, 216 were treated with MTX at the onset of LPD and 144 (66.7%) achieved SR after MTX discontinuation. Higher MTX doses, high titers of anti-CCP antibodies (>13.5 U/mL), and lower LDH and soluble IL-2 receptor levels were associated with SR. Lymphocyte count was decreased at LPD onset and increased at 2 weeks after MTX discontinuation in the SR group. Epstein-Barr virus-positive mucocutaneous ulcer, reactive lymphoid hyperplasia and unclassifiable B-cell lymphoma, were more frequent in the SR than in the non-SR group. In multivariable analysis, diffuse large B-cell lymphomas was an independent predictive factor for non-SR. In the patients with SR, 73.9% achieved partial or complete regression as early as 2 weeks after MTX discontinuation. CONCLUSION: SR and non-SR in RA patients with LPDs after MTX discontinuation were associated with certain clinical characteristics.

Treatment of rheumatoid arthritis after regression of lymphoproliferative disorders in patients treated with methotrexate: a retrospective, multi-center descriptive study.

OBJECTIVES: To identify the optimal treatment for rheumatoid arthritis (RA) after the regression of lymphoproliferative disorders (LPDs). METHODS: The subjects were 232 patients with RA who developed LPD between 2000 and 2017 at seven hospitals participating in the LPD-WG study. Kaplan-Meier and Cox proportional regression analyses were performed to determine the factors associated with the rate of LPD relapse and the retention of biological disease-modifying antirheumatic drugs (bDMARDs). RESULTS: Treatment for RA was resumed in 138 patients after spontaneous regression of LPD after the discontinuation of methotrexate and in 52 patients after chemotherapy for LPD (persistent-LPD). LPD relapses occurred in 23 patients. Not DMARDs use but Hodgkin's lymphoma was identified as a risk factor for LPD relapse. In 88 RA patients treated with bDMARDs [tocilizumab, 39 patients; abatacept 20 patients; tumor necrosis factor inhibitor, 29 patients], the one-year retention rate was 67.8%. The risk factors for discontinuation of bDMARDs were persistent-LPD, non-diffuse large B-cell lymphomas (non-DLBCL), and a high clinical disease activity index (CDAI). Tocilizumab showed the highest retention rate among bDMARDs, particularly in DLBCL. CONCLUSION: Although any bDMARD could be used in patients after LPD regression, effectiveness and risk for relapse should be carefully assessed for each LPD subtype.