Risk factors associated with relapse after methotrexate dose reduction in patients with rheumatoid arthritis receiving golimumab and methotrexate combination therapy.

AIM: To identify risk factors for relapse after methotrexate (MTX) dose reduction in rheumatoid arthritis (RA) patients receiving golimumab (GLM)/MTX combination therapy. METHOD: Data on RA patients ≥20 years old receiving GLM (50 mg) + MTX for ≥6 months were retrospectively collected. MTX dose reduction was defined as a reduction of ≥12 mg from the total dose within 12 weeks of the maximum dose (≥1 mg/wk average). Relapse was defined as Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) score ≥3.2 or sustained (≥ twice) increase of ≥0.6 from baseline. RESULTS: A total of 304 eligible patients were included. Among the MTX-reduction group (n = 125), 16.8% of patients relapsed. Age, duration from diagnosis to the initiation of GLM, baseline MTX dose, and DAS28-CRP were comparable between relapse and no-relapse groups. The adjusted odds ratio (aOR) of relapse after MTX reduction was 4.37 (95% CI 1.16-16.38, P = 0.03) for prior use of non-steroidal anti-inflammatory drugs (NSAIDs), and the aORs for cardiovascular disease (CVD), gastrointestinal disease and liver disease were 2.36, 2.28, and 3.03, respectively. Compared to the non-reduction group, the MTX-reduction group had a higher proportion of patients with CVD (17.6% vs 7.3%, P = 0.02) and a lower proportion of prior use of biologic disease-modifying antirheumatic drugs (11.2% vs. 24.0%, P = 0.0076). CONCLUSION: Attention should be given to RA patients with history of CVD, gastrointestinal disease, liver disease, or prior NSAIDs-use when considering MTX dose reduction to ensure benefits outweigh the risks of relapse.

Successful early introduction of mepolizumab for peripheral neuropathy with a peripheral circulatory disorder in a patient with myeloperoxidase anti-neutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis.

A 26-year-old woman presented with abdominal pain, diarrhoea, vomiting, fever, and progressive paralysis in the lower limbs. She had a history of bronchial asthma and experienced sinusitis, progressive peripheral neuropathy, polyarthritis, and leukocytosis with prominent eosinophilia. The patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA). Abdominal pain was considered to be an ischaemic enteritis associated with EGPA. She was administered 1,000 mg/day of methylprednisolone for 3 days and intravenous immunoglobulin (400 mg/kg/day of γ-globulin for 5 days) followed by 50 mg (1 mg/kg)/day of oral prednisolone due to rapidly progressing peripheral neuropathy. Her symptoms temporarily improved; however, peripheral neuropathy recurred after a week, and the eosinophil count increased. Eighteen days after following the resumed treatment, 300 mg of mepolizumab, a humanised monoclonal antibody, was administered. Subjective symptoms, nerve conduction velocity, and skin perfusion pressure (an index of peripheral circulation in the lower extremities) improved after 4 weeks. Although mepolizumab has been approved for EGPA, there is no evidence of its efficacy against peripheral neuropathy. Early introduction of mepolizumab may contribute to an the early improved progressive peripheral neuropathy with eosinophilia.

Comparison of Composite Measure Remission Targets in Psoriatic Arthritis.

OBJECTIVE: To identify (1) which composite measure is the most stringent target of remission; and (2) which disease component target proves the most difficult to achieve in the different states of minimal disease activity (MDA), Composite Psoriatic Disease Activity Index (CPDAI), Disease Activity Index for Psoriatic Arthritis (DAPSA), and clinical DAPSA (cDAPSA) in patients with psoriatic arthritis (PsA). METHODS: There were 258 patients with PsA recruited. Disease remission was evaluated comparing 4 different composite measures and using remission cutoffs as previously proposed (very low disease activity [VLDA], CPDAI ≤ 2, DAPSA ≤ 4, cDAPSA ≤ 4). RESULTS: Patients met VLDA criteria (MDA 7/7) in 9.0% of visits, DAPSA remission in 19.8%, cDAPSA remission in 23.4% and CPDAI remission in 30.2%. Of 258 patients, MDA criteria (≥ 5/7) were fulfilled in 46.5%. Of those in MDA, VLDA criteria were reached in 25.0%. Patients met the pain visual analog scale (VAS) target in 57.5% of visits when they were in MDA, 43.3% when in low disease activity (MDA 5-6/7), and 44.8% when in CPDAI remission. Multivariate regression analysis revealed that pain VAS was the least likely target to be achieved. Patients with inflammatory-type back pain had significantly higher pain scores; further, a significant relationship was seen between Bath Ankylosing Spondylitis Disease Activity Index and pain VAS. CONCLUSION: Based on our analysis, VLDA proved the most stringent target of disease remission in PsA compared to CPDAI, DAPSA, and cDAPSA. The pain VAS target of ≤ 1.5 cm was the most difficult component to achieve. CPDAI ≤ 2 was found to be the least stringent remission target; however, measurements of axial involvement, which contributed to the elevated pain VAS score in patients not achieving VLDA, were included as a domain in CPDAI only.

Guselkumab improves joint pain in patients with pustulotic arthro-osteitis: A retrospective pilot study.

Pustulotic arthro-osteitis (PAO) is an osteoarticular complication of palmoplantar pustulosis (PPP). Although guselkumab, an anti-interleukin-23p19 antibody, has been shown to be effective for PPP, its efficacy for PAO is still not well understood. We conducted a retrospective observational study to evaluate the effectiveness of 28-week guselkumab treatment for five PAO patients in daily clinical practice. Four patients had sternoclavicular arthritis, and one had only sacroiliitis. Guselkumab improved pain visual assessment scale scores in all five patients by 54.2% (11.1-87.5%) on average at week 28 compared with baseline, and discontinuation or dose reduction of analgesics was possible in four of them. Three patients showed clinically significant improvement in Bath Ankylosing Spondylitis Disease Activity Index of 2 or more. On the other hand, beneficial change in Ankylosing Spondylitis Disease Activity Score of 1.1 or more was observed in only one patient. Bone scintigraphy demonstrated decreased uptake in sternoclavicular joints after guselkumab treatment in all four patients with sternoclavicular arthritis. Improvement of Palmoplantar Pustulosis Area and Severity Index was also confirmed. Guselkumab can be a treatment option for intractable PAO.

Salivary Gland Focus Score Is Associated With Myocardial Fibrosis in Primary Sjögren Syndrome Assessed by a Cardiac Magnetic Resonance Approach.

OBJECTIVE: The risk of clinically manifested major cardiovascular (CV) events in primary Sjögren syndrome (pSS) remains unclear. This study aimed to assess myocardial fibrosis in pSS and investigate the associated disease characteristics by cardiac magnetic resonance imaging (cMRI). METHODS: We performed a cross-sectional study of patients with pSS without cardiac symptoms. Labial gland biopsy was documented in 44 patients (85%). Patients without CV risk factors underwent contrast-enhanced cMRI. Late gadolinium enhancement (LGE) was used to assess myocardial fibrosis. Myocardial edema was assessed using T2-weighted imaging (T2WI). We compared the left ventricular (LV) geometry and function between the groups with and without LGE. Further, we explored the associations of cMRI abnormalities with pSS characteristics. RESULTS: Fifty-two women with pSS (median age 55, IQR 47.0-65.7 yrs) were enrolled in the study. LGE was observed in 10 patients (19%), two of whom showed high intensity on T2WI. High intensity on T2WI was observed in 3 patients (5.8%). LV mass index and LV mass/end-diastolic volume tended to be higher in the LGE-positive group than in the LGE-negative group (P = 0.078 and 0.093, respectively). Salivary gland focus score (FS) ≥ 3 was independently associated with LGE-positive in the multivariable analysis (OR 11.21, 95% CI 1.18-106.80). CONCLUSION: Subclinical myocardial fibrosis, as detected by cMRI, was frequent in patients with pSS without cardiac symptoms. Abnormal cMRI findings were associated with salivary gland FS ≥ 3.

Impact of biological treatment on left ventricular dysfunction determined by global circumferential, longitudinal and radial strain values using cardiac magnetic resonance imaging in patients with rheumatoid arthritis.

AIM: To evaluate left ventricular (LV) dysfunction in patients with rheumatoid arthritis (RA) and to determine the impact of biological treatment on LV function in these patients using global circumferential strain (GCS), global longitudinal strain (GLS) and global radial strain (GRS) values assessed by feature tracking cardiac magnetic resonance (FT-CMR) imaging. METHODS: Eighty patients with RA and 20 controls without cardiovascular disease underwent non-contrast CMR imaging. Patients with RA received conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs (bDMARDs). Global strains were calculated in 16 LV segments. RESULTS: No significant differences in cardiovascular risk factors were found between the RA group and controls. GCS was 21% lower in the RA group compared with controls (P < 0.001) and was 14% lower in the csDMARDs group compared with the bDMARDs group (P = 0.002), whereas, there was no significant difference in GLS and GRS between the RA group and the controls. In regard to strain rates, diastolic GCS and GRS rates were significantly lower in the RA group (P < 0.001, 0.011, respectively). In univariate analyses, GCS was significantly associated with the Simplified Disease Activity Index, bDMARDs, swollen joint count, anti-cyclic citrullinated peptides antibodies and matrix metalloproteinase-3, but in multivariable analysis, only bDMARDs was significantly associated with GCS (P = 0.021). CONCLUSION: Global circumferential strain, GLS and GRS assessed by FT-CMR can reveal subclinical LV dysfunction in patients with RA. Furthermore, they can be used to determine the normalization of LV regional dysfunction induced by bDMARDs possibly related to disease activity reduction.

Efficacy and safety of minodronic acid hydrate in patients with steroid-induced osteoporosis.

OBJECTIVES: Minodronic acid hydrate, an oral bisphosphonate, has a greater inhibitory effect on bone resorption than do other approved drugs; however, this has been studied only in patients with primary osteoporosis. Here, we administered minodronic acid hydrate to patients with steroid-induced osteoporosis who have been treated with steroids for rheumatoid arthritis or other collagen diseases, and the efficacy and safety of minodronic acid hydrate were prospectively investigated. METHODS: Twenty-five patients treated in our rheumatology clinic received minodronic acid hydrate 1 mg/day. The changes in bone mineral density (BMD) and bone turnover markers were investigated at 3 and 6 months, and adverse events, including the presence or absence of an incident osteoporotic fracture, were examined over a period of 6 months. RESULTS: Percent changes in BMD of the lumbar spine and femur significantly increased. The values of bone turnover markers significantly decreased. There were no patients with a radiographically apparent incident fracture. Adverse events included toothache for which the patient discontinued the treatment and three cases of gastrointestinal disorder that did not lead to discontinuation, and thus minodronic acid hydrate was well tolerated. CONCLUSIONS: Here, we show that minodronic acid hydrate is effectively and safely used for treatment of steroid-induced osteoporosis.

Self-assembly formed by a short DNA probe pair: Application for highly sensitive mRNA species detection without reverse transcription.

We describe a novel technology for detecting nucleic acids: Probe Alteration Link Self-Assembly Reactions (PALSAR). PALSAR comprises DNA self-assembly of pairs of short DNA probes formed by alternate hybridization of three complementary regions in a pair of honeycomb probes (HCPs). Self-assembly occurs at designated salt concentrations and reaction temperatures and requires no enzymes. We prepared pairs of HCPs to detect mRNAs encoded by the GAPDH gene ß-actin (BA) gene, CD3D gene, CD4 gene, major vault protein (MV) gene and the signalling lymphocytic activation molecule-associated protein (SAP) gene, and succeeded in quantitatively detecting these mRNAs. PALSAR could detect mRNA directly without synthesizing cDNA. Moreover, multiple mRNAs could be detected simultaneously in a single reaction tube and there was a good correlation between the results obtained PALSAR and those by real-time PCR.

[Diagnostic value of brain biopsy in intravascular large B-cell lymphoma mimicking progressive multifocal leukoencephalopathy: case report].

We report a 68-years-old woman with systemic sclerosis and interstitial pneumonia (IP). She had developed subacute progressively encephalopathy and dementia while treated with oral cyclophosphamide and prednisolone. She admitted to our hospital because of syncope. Laboratory tests indicated slight elevated cerebrospinal fluid protein, and levels of serum C-reactive protein (CRP), levels of soluble IL-2 receptor was normal. But, magnetic resonance imaging (MRI) of the brain showed multiple infarct-like lesions mainly in the white matter, which mimics progressive multiple leukoencephalopathy (PML). Twenty days after admission, the retested MRI of the brain disclosed initial lesions progressively enlarged and numbers of the lesions were increased. The polymerase chain reaction (PCR) for JC virus of cerebrospinal fluid was negative. To make diagnosis, brain biopsy was performed. Microscopic examination revealed that small vessels were filled with lymphoma cells (CD20+, CD79+, CD3-), and intravascular lymphoma (IVL) was diagnosed. She treated with regimens of R-CHOP. After chemotherapy her consciousness and dementia were gradually improved. IVL of central nerve system (CNS) is a rare disease, and its common symptoms are ischemia, infarction and dementia. Diagnosis of IVL of CNS is difficult when the lesion mimics PML, and patient with similar laboratory examinations and radiographic findings of PML should undergo brain biopsy detected malignant cell in small vessels, which is a value of diagnosis.