Biological/targeted synthetic DMARDs do not arrest bone loss in patients with rheumatoid arthritis: a multicenter prospective observational study.

OBJECTIVE: To elucidate the differential effects of biological/target synthesized DMARDs (b/tsDMARDs) on bone metabolism in patients with rheumatoid arthritis (RA) in a real-world cohort. METHODS: This was a multicentre prospective observational study of RA patients enrolled at the time of 1st b/tsDMARDs administration. Bone mineral density (BMD) and bone turnover markers (BTMs) were measured during the 52-week observation. The study was designed to enrol all eligible RA patients. The end-points were differences in changes in BMD according to b/tsDMARD type, and the correlation between BMD and BTMs. RESULTS: A total of 1,164 patients were enrolled in this study. b/tsDMARDs improved RA disease activity from mean CDAI 25.5 at baseline to 4.5 at week 26. Patients not receiving anti-osteoporotic agents (anti-OP) at baseline with no history of fracture experienced a significant decrease in both femoral neck (F: mean 0.666-0.655 g/cm3) and radial (R: 0.518-0.514) BMD at week 26. Despite maintaining low CDAI levels during weeks 26-52 (5.3-4.4), there was a continued decline in BMD (F: 0.653, R: 0.509. Weeks 52). None of b/tsDMARDs type preserved BMD. Conversely, patients receiving anti-OP at baseline maintained stable BMD throughout the study (Weeks 0/26/52. F: 0.551/0.551/0.555, R: 0.415/0.416/0.415). Although BTMs were changed by b/tsDMARDs, the changes were unrelated to those in BMD. CONCLUSION: Our study suggested the progression of osteoporosis in RA patients during b/tsDMARDs treatment without anti-OP. BTMs may not reflect BMD change. Regular monitoring of BMD in RA should be considered for early management of osteoporosis.

Usefulness of ultrasound as a predictor of elderly-onset rheumatoid arthritis with polymyalgia rheumatica-like onset.

OBJECTIVES: Differentiation between polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis (EORA), especially in elderly patients, is often difficult due to similarities in symptoms and serological kinetics. In this study, we aimed to analyse the predictors of EORA with PMR-like onset. METHODS: Seventy-two patients diagnosed with PMR, who attended our hospital for routine care and underwent musculoskeletal ultrasonography at that time were evaluated. Synovitis was evaluated semi-quantitatively (0-3) by grey scale (GS) and power Doppler (PD) in 24 joints [both hands (wrist, metacarpophalageal, and proximal interphalangeal joints) and both shoulder joints]. RESULTS: Overall, 18 patients had rheumatoid arthritis (25.0%); the mean age was 75.0 years, and 34.7% and 65.3% were male and female, respectively. In PMR and PMR/EORA groups, multivariate logistic analysis showed that rheumatoid factor positivity, GS ≥2 of hand joints, and PD ≥1 of hand joints were independent factors with significant differences. At least one of the three factors had a sensitivity of 88.9% and specificity of 92.6%. CONCLUSIONS: The presence of at least one of the criteria: rheumatoid factor positivity, GS ≥ 2, and PD ≥ 1 of hand joints, suggested the possibility of developing EORA within 1 year of PMR diagnosis.

A case of giant cell arteritis complicated by polymyalgia rheumatica with scalp necrosis and refractory jaw claudication.

Scalp necrosis is a rare complication of giant cell arteritis (GCA); however, it is a predictor of severe disease. In this case study, a patient presented with GCA complicated by polymyalgia rheumatica with scalp necrosis. An 86-year-old woman was admitted to the hospital for pulsating headache, scalp pain, jaw claudication, and generalised pain. Bilateral temporal arteries were found to be distended and pulseless, and scalp necrosis was observed in the parietal region. Simultaneous high-resolution contrast-enhanced magnetic resonance imaging (MRI) sequences of the head, shoulder, and hip showed staining around the bilateral shallow temporal arteries, shoulder, and hip joints, which was confirmed as GCA with polymyalgia rheumatica using other examination findings. After treatment with early induction remission therapy, scalp necrosis healed, but jaw claudication persisted. Six months after the start of treatment, scalp necrosis was cured to full hair growth. Despite remission induction therapy combined with tocilizumab, the patient had persistent jaw claudication for several months. At that time, a high-resolution contrast-enhanced MRI re-examination was useful in assessing disease activity. GCA with scalp necrosis may cause prolonged jaw claudication reflecting the progression of ischaemic lesions, whereas the disease activity can be accurately assessed by combining MRI studies.

Rituximab in remission induction and maintenance therapy for microscopic polyangiitis associated with gastric cancer: A case report.

We herein report a case of a patient with gastric cancer-associated microscopic polyangiitis (MPA) who was treated with combination glucocorticoids and rituximab (RTX) for remission induction and maintenance, and finally to discontinue glucocorticoids without recurrence of gastric cancer or MPA in a year. A 69-year-old man was suspected of having MPA because of fever, high C-reactive protein levels, neuritis, and a high titer of myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA). Upper gastrointestinal endoscopy indicated early-stage gastric cancer, for which he underwent surgery preceded by immunosuppressive therapy for vasculitis. Histopathological images showed vasculitis in the vicinity of the cancerous tissue, suggesting an association between gastric cancer and vasculitis. Postoperatively, fever and inflammatory response improved, but MPO-ANCA increased further and the patient developed alveolar hemorrhage. He resulted in remission with high-dose glucocorticoids and RTX, and he received maintenance therapy with RTX without additional immunosuppressive agents. After 1 year of treatment, he was able to discontinue glucocorticoids without recurrence of gastric cancer or vasculitis. There is no established treatment for malignancy-associated vasculitis other than glucocorticoids. Although more cases need to be accumulated in the future, RTX is expected to be useful in malignancy-associated vasculitis.

Association between ultrasound images and patient-reported outcomes in the treatment of rheumatoid arthritis: a retrospective study.

BACKGROUND: Improvements in the treatment of rheumatoid arthritis (RA) have made it possible to achieve treatment goals. It has been reported that both residual synovitis caused by RA and the patients' subjective symptoms remain even after achieving the treatment goals; however, there are limited reports showing a relationship between them. Furthermore, no studies have evaluated the relationship between patient-reported outcomes (PROs) and subclinical synovitis measured by musculoskeletal ultrasonography (MSUS) in the treatment of RA. This study aimed to investigate residual symptoms and residual synovitis due to remission (REM) or low disease activity (LDA). METHODS: We performed MSUS on 300 patients with RA who attended our hospital for routine care, and we analysed them cross-sectionally by disease activity. Grayscale (GS) and power Doppler (PD) synovitis was evaluated in 22 bilateral hand joints using MSUS. We first performed univariate and multivariate analysis by dividing the data by disease activity. Next, we analysed each PRO in the obtained MSUS results. RESULTS: A multivariate analysis of high disease activity (HDA)/moderate disease activity (MDA) vs. LDA/ REM group identified tender joint count (TJC), pain visual analog scale (VAS) score, and presence or absence of GS score ≥ 2. The one-way analysis of the relationship between the presence or absence of GS score ≥ 2 and each PRO showed a significant difference. In contrast, a multivariate analysis of LDA vs. REM group identified TJC and fatigue VAS score. In REM, PROs alone were relevant, and there was no correlation with MSUS. CONCLUSION: We found that the residual inflammation in the ultrasound images was associated with PROs in the LDA group, but not in the REM group. Trial registration Retrospectively registered.

Rapidly progressive glomerulonephritis after introduction of certolizumab pegol: a case report.

Tumour necrosis factor (TNF) inhibitors are used against a variety of connective tissue diseases, including rheumatoid arthritis. Contrarily, although rare, TNF inhibitors are known to induce autoimmune diseases, such as systemic lupus erythematosus and psoriasis as a paradoxical reaction. We experienced a case of rapidly progressive glomerulonephritis after introduction of certolizumab pegol. The patient was a 30-year-old woman who was previously diagnosed with rheumatoid arthritis in X-8. She received treatment with methotrexate (8 mg/week) and infliximab (3 mg/kg/8 weeks), following which she showed low disease activity and remission. In September X-1, methotrexate and infliximab were discontinued and certolizumab pegol was introduced because she desired to bear children. In March X, the patient experienced renal dysfunction, and urinary protein analysis revealed positivity for myeloperoxidase anti-neutrophil cytoplasmic autoantibody. Renal biopsy showed crescentic glomerulonephritis, and the patient was diagnosed with rapidly progressive glomerulonephritis due to TNF inhibitor-induced microscopic polyangiitis. As she desired to bear children, rituximab was introduced in addition to corticosteroids, which led to remission of the symptoms. TNF inhibitors should be discontinued in patients who develop rapidly progressive glomerulonephritis, and these patients should be treated with immunosuppressive drugs, such as massive corticosteroids and cyclophosphamide. In the present case, rituximab was useful for not only the treatment, but also for the preservation of fertility.

Short-term effectiveness of ixekizumab to refractory psoriatic arthritis with spondyloarthritis: two case reports.

Psoriatic arthritis (PsA) manifests not only skin lesion but also peripheral and axial joint involvements, thus the disease is considered to be part of spondyloarthritis. In patients with active spondyloarthritis, tumour necrosis factor inhibitors biologics are often considered, but there is not sufficient evidence about other type of biologics. Ixekizumab (IXE) is a humanised monoclonal antibody, which acts against interleukin-17A, a cytokine involved in psoriasis pathogenesis. IXE was administered to two patients with refractory PsA, manifested via extended skin lesions and complicated by axial joint involvement. The effectiveness and imaging results during 12 weeks of treatment were assessed. IXE improved disease activity in both a tumour necrosis factor inhibitors biologics-inadequate responder and a bio-naïve patient and, consequently, IXE probably plays a key role in treatment of axial disease of PsA.

Severe pulmonary arterial hypertension and interstitial pneumonia related to systemic lupus erythematosus successfully treated with mycophenolate mofetil: A novel case report.

BACKGROUND: Pulmonary arterial hypertension (PAH) and interstitial pneumonia (IP) are relatively rare complications of systemic lupus erythematosus (SLE) and are associated with a poor prognosis. Overcoming these complications is a challenge for improving the prognosis. CASE REPORT: A 41-year-old woman was diagnosed with SLE complicated by IP at the age of 21 years and with antiphospholipid syndrome at the age of 32 years at another hospital. She had been administered prednisolone (PSL) at a dose ≥15 mg daily, as well as various immunosuppressants and antiplatelet/anticoagulation therapy. On day I of hospitalization, She presented to our emergency outpatient department with fever, marked dyspnea, and skin ulcer on the left lower leg and was admitted the same day. Chest radiography revealed marked cardiomegaly and interstitial shadow, and right heart catheterization showed elevation in the mean pulmonary arterial pressure to 47 mmHg, indicating PAH. While oxygen therapy was started, high-dose steroid therapy and mycophenolate mofetil (MMF) were administered for treatment of SLE complicated by PAH/IP, and prostacyclin (prostaglandin I2), endothelin receptor antagonist, and PDE5 inhibitor were administered for PAH. Both SLE disease activity and PAH/IP improved and were maintained with no exacerbation for 2 years. The PSL dose could eventually be reduced to 5 mg/day. CONCLUSION: In SLE complicated by PAH/IP, reports on the efficacy of MMF are scarce, and our findings suggested that MMF may be a treatment option in such cases.

Fifty-Two-Week Results of Clinical and Imaging Assessments of a Patient with Rheumatoid Arthritis Complicated by Systemic Sclerosis with Interstitial Pneumonia and Type 1 Diabetes despite Multiple Disease-Modifying Antirheumatic Drug Therapy That Was Successfully Treated with Baricitinib: A Novel Case Report.

Baricitinib is a Janus kinase 1/2 (JAK1/2) inhibitor used in the treatment of rheumatoid arthritis. A 71-year-old woman with rheumatoid arthritis complicated by systemic sclerosis and type 1 diabetes that were resistant to multiple disease-modifying antirheumatic drugs started treatment with baricitinib. After baricitinib administration, the disease activity of her rheumatoid arthritis was attenuated from the early stage of treatment, and the effect was maintained for up to 52 weeks. In addition, the skin sclerosis in systemic sclerosis showed an improvement. Regarding the influence on type 1 diabetes, the required daily dose of insulin and hemoglobin A1c (HbA1c) levels decreased. To date, no studies have demonstrated the effectiveness of baricitinib on systemic sclerosis or type 1 diabetes. We report that baricitinib was effective for systemic sclerosis and type 1 diabetes, as well as for rheumatoid arthritis, for up to 52 weeks.

Clinically relevant radiographic progression in joint destruction in RA patients with abnormal MMP-3 or high levels of CRP despite 1-year treatment with infliximab.

OBJECTIVE: Identify the independently related factors of joint destruction progression in RA patients despite of infliximab treatment. METHODS: The subjects were cases who underwent infliximab treatment for one year or longer in our department (n = 244). Patients in which modified total sharp score (mTSS), joint erosion (JE), and joint space narrowing (JSN) had advanced to the standard value (3.0) or more for one year were defined as mTSS- Clinically-Relevant-Rapid Progression (CRRP) (n = 20), JE-CRRP (n = 20), and JSN-CRRP (n = 23), and the respective related factors at baseline and week 54 were defined by multiple logistic regression. RESULTS: The median disease duration was 24 months and median mTSS 9.0 at baseline. The median DAS28, CRP, and yearly progression of mTSS improved from 5.8 to 2.6, 1.2 to 0.1 mg/dL, and 4.4 to 0.0 point/year, respectively. The related factor in each of mTSS-CRRP, JE-CRRP, and JSN-CRRP was high CRP levels at baseline. At week 54, the related factor of mTSS-CRRP and JSN-CRRP was high MMP-3 titer; however, the related factor of JE-CRRP was high CRP levels. CONCLUSION: High CRP levels at baseline were an independent predictive factor of joint destruction advancement during infliximab treatment. Moreover, it was believed that abnormal MMP-3 at week 54 was the index for mTSS and JSN advancement, while high CRP levels were the index for JE advancement.

Low complements and high titre of anti-Sm antibody as predictors of histopathologically proven silent lupus nephritis without abnormal urinalysis in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to clarify the clinical characteristics and predictors of silent LN (SLN), a type of LN in SLE without abnormal urinalysis or renal impairment. METHODS: Of 182 patients who underwent renal biopsy, 48 did not present with abnormal urinalysis or renal impairment at the time of biopsy. The patients with LN (SLN group, n = 36) and those without LN (non-LN group, n = 12) were compared with respect to their baseline characteristics. Bivariate analysis comprised Fisher's exact test and the Mann-Whitney test, whereas multivariate analysis employed binomial logistic regression analysis. RESULTS: LN was histopathologically identified in 36 of 48 patients. According to the International Society of Nephrology/Renal Pathology Society classification, 72% of the SLN patients were classified as having class I/II, with a further 17% having class III/IV. Bivariate analyses indicated that platelet count, serum albumin, complement components (C3 and C4), complement haemolytic activity (CH50), anti-Sm antibody titre and anti-ribonucleoprotein antibody titre were significantly different between groups. Multivariate analysis indicated that CH50 and C3 titres were significantly lower in the SLN group, whereas anti-Sm antibody titre was significantly higher. The cut-off titre, calculated based on the receiver operating characteristic curve for CH50, was 33 U/ml, with a sensitivity and specificity of 89% and 83%, respectively. The cut-off titre for anti-Sm antibodies was 9 U/ml, with a sensitivity and specificity of 74% and 83%, respectively. CONCLUSION: Low titres of CH50 and C3 and a high titre of anti-Sm antibody were identified as predictors of SLN.

Prophylaxis for Pneumocystis pneumonia in patients with rheumatoid arthritis treated with biologics, based on risk factors found in a retrospective study.

INTRODUCTION: Pneumocystis pneumonia (PCP) is one of the most prevalent opportunistic infections in patients undergoing immunosuppressive therapy. In this article, we discuss risk factors for PCP development in patients with rheumatoid arthritis (RA) during the course of biologic therapy and describe a prophylactic treatment for PCP with trimethoprim/sulfamethoxazole (TMP/SMX). We also evaluate the effectiveness and safety of the treatment. METHODS: We retrospectively analyzed 702 RA patients who received biologic therapy and compared the characteristics of patients with vs. without PCP to identify the risk factors for PCP. Accordingly, we analyzed 214 patients who received the TMP/SMX biologic agents as prophylaxis against PCP at the start of treatment to evaluate their effectiveness and safety. RESULTS: We identified the following as risk factors for PCP: age at least 65 years (hazard ratio (HR) = 4.37, 95% confidence interval (CI) = 1.04 to 18.2), coexisting pulmonary disease (HR = 8.13, 95% CI = 1.63 to 40.0), and use of glucocorticoids (HR = 11.4, 95% CI = 1.38 to 90.9). We employed a protocol whereby patients with two or three risk factors for PCP would receive prophylactic treatment. In the study with 214 patients, there were no cases of PCP, and the incidence of PCP was reduced to 0.00 per 100 person-years compared with that before the procedure (0.93 per 100 person-years). There were no severe adverse events induced by the TMP/SMX treatment. CONCLUSIONS: RA patients with two or three risk factors for PCP who are receiving biologic therapy can benefit from safe primary prophylaxis.

Efficacy and safety of reducing duration of infliximab infusion.

OBJECTIVE: To evaluate the safety and efficacy of reducing the duration of infliximab infusion for rheumatoid arthritis (RA) treatment. METHODS: The first 6 infliximab infusions were each administered over a 2-h period. If no adverse reaction was observed, infusion times were shortened to 1 h starting with the seventh infusion with further shortening to 30 min starting with the thirteenth infusion. Subjects were divided into two groups: shortened infusion time group, in which infusion times were shortened as above; and constant infusion time group, in which infusion time was 2 h. Incidence of infusion reactions and improvement in disease activity score for 28 joints (DAS-28) erythrocyte sedimentation rate (ESR) for total infusions were compared for the seventh to twelfth and thirteenth to eighteenth infusions. RESULTS: The incidences of infusion reactions after the seventh to twelfth and thirteenth to eighteenth infusions in the shortened infusion time group were 0.53% and 0.58%, respectively. In the constant infusion time group, these were 0.70% and 0.67%, respectively. Furthermore, shortening the infusion duration did not affect the DAS-28 (ESR) improvement rate. CONCLUSIONS: We established that this stage-wise shortening of infusion duration, first to 1 h and then to 30 min, did not compromise the safety or efficacy of treatment.

Study on the safety and efficacy of tocilizumab, an anti-IL-6 receptor antibody, in patients with rheumatoid arthritis complicated with AA amyloidosis.

OBJECTIVES: Although treatment of rheumatoid arthritis (RA) has progressed by the use of biologics, amyloid A (AA) amyloidosis is still an intractable complication in patients with RA. In the present study, safety and efficacy of 1-year treatment with an anti-IL-6 receptor antibody tocilizumab (TCZ) on RA and AA amyloidosis were estimated. METHODS: TCZ (8 mg/kg every 4 weeks) was administered to five RA patients complicated with AA amyloidosis. The primary end point was improvement in renal dysfunction and the secondary end point was CDAI at 1 year after the treatment. RESULTS: An improvement in the renal dysfunction, including urinary protein secretion, was found, in four patients including two patients who were refractory to etanercept, with a remarkable decrease of SAA concentration, and the progression of organ dysfunction was prevented at 1 year in all patients treated with TCZ. The mean clinical disease activity index decreased from 33.9 to 4.7 (p = 0.012) in five patients treated with TCZ for 1 year. Three non-serious adverse events were observed in two patients. CONCLUSIONS: TCZ ameliorates renal dysfunction in RA patients complicated with AA amyloidosis who are refractory to conventional therapies, thereby suggesting that TCZ has a potential to regulate AA amyloidosis.

Effect of interleukin-6 receptor inhibitor, tocilizumab, in preventing joint destruction in patients with rheumatoid arthritis showing inadequate response to TNF inhibitors.

OBJECTIVES: To examine the effectiveness of tocilizumab (TCZ) in preventing joint destruction in patients with inadequate response to tumor necrosis factor inhibitors (TNF-IR) by assessing X-rays. METHODS: RA patients were extracted from the Retrospective actemra investigation for optimal needs of RA patients (REACTION) study. Parameters and components of disease activity were evaluated during anti-TNF treatment and during TCZ treatment. X-ray images of hands and feet at the beginning of this study during anti-TNF treatment (Pre), at the start point of TCZ treatment (Baseline) and after TCZ treatment (Post) were collected for assessing joint destruction. RESULTS: Forty-five patients from the REACTION study fulfilled the criteria of clinical TNF-IR. During anti-TNF treatment, mean DAS28-ESR rose from 5.35 to 5.87 (mean observation duration, 16 months) but improved significantly to 2.94 (P < 0.0001) at 52 weeks after switching to TCZ. Mean change in van der Heijde-modified Sharp score (TSS) during anti-TNF treatment was 3.17 in this TNF-IR population. After switching to TCZ, mean change in TSS was 1.20 (P < 0.05). Rate of radiographic non-progression improved to 66.7% during TCZ treatment from 40.0% during anti-TNF treatment. The predictive factor for no radiographic progression after switching to TCZ was a HAQ disability index (HAQ-DI) score of ≤ 1.88 at switching to TCZ. CONCLUSION: TCZ was a good treatment option for improving signs and symptoms and inhibiting progression of joint damage in patients with clinical and structural TNF-IR.

Abatacept inhibits radiographic progression in patients with rheumatoid arthritis: a retrospective analysis of 6 months of abatacept treatment in routine clinical practice. The ALTAIR study.

OBJECTIVES: Our objectives in this study were to determine the inhibitory effects of abatacept on joint damage and its clinical efficacy and safety in patients with rheumatoid arthritis (RA). METHODS: Fifty Japanese patients with RA were treated with abatacept for 24 weeks in routine clinical practice. RESULTS: At week 24, 20 % of patients achieved clinical remission [Simplified Disease Activity Index (SDAI) ≤3.3], whereas 50 % were in remission or had a low disease activity. Structural remission [progression of modified total Sharp score (ΔmTSS) ≤0.5] was achieved in 76 % of patients. The ΔmTSS decreased significantly from 7.1 ± 7.3 at baseline to 1.8 ± 5.7 at week 24. C-reactive protein (CRP) was the only independent prognostic factor for joint damage progression at week 24, whereas SDAI and matrix metalloproteinase-3 levels were not. A very high proportion of patients with CRP levels <1.5 mg/dl (88 %) achieved structural remission. In terms of safety, the retention rate for all patients was favorable (80 %), and stomatitis was the only adverse event observed. No patient withdrew from the study because of infections. CONCLUSIONS: Abatacept has favorable clinical and structural effects, inhibits radiographic progression, and has a good safety profile in routine clinical practice.

Discontinuation of adalimumab after attaining disease activity score 28-erythrocyte sedimentation rate remission in patients with rheumatoid arthritis (HONOR study): an observational study.

INTRODUCTION: Evidences of biologics-free disease control after discontinuing adalimumab (ADA) in rheumatoid arthritis (RA) patients in clinical practice have not been sufficiently investigated. Purpose of this study is to investigate whether disease activity score 28 (DAS28)- erythrocyte sedimentation rate (ESR) remission was preserved after discontinuation of ADA in patients with RA. METHODS: This is an observational but not a randomized controlled study. Among 197 RA patients who initiated with combination of ADA with concomitant MTX, 69 (35%) acquired DAS28 (ESR) < 2.6 for at least 24 weeks. Of those 69 patients, 51 went on ADA discontinuation with their consent, and finally 50 of those with follow-up of > 24 weeks were evaluated. The effect of discontinuing ADA on clinical disease activity, functional disability and radiographic progression were evaluated by DAS28 (ESR), the clinical disease activity index (CDAI) and the simplified disease activity index (SDAI), by a health assessment questionnaire-disability index (HAQ-DI) and by the modified total Sharp score (mTSS), respectively. RESULTS: The mean age of the participants was 59.5 years with the mean disease duration of 7.1 years. Out of the 50 patients, 29 (58%) were maintained in DAS28 (ESR) < 2.6 at 24 weeks after discontinuing ADA. A logistic regression analysis showed that DAS28 (ESR) at baseline significantly predicted a DAS28 (ESR) < 2.6 maintained after discontinuation of ADA, and a receiver-operating characteristic (ROC) analysis showed that the cut-off value of DAS28 (ESR) at discontinuation was 2.16. The mean HAQ-DI at six months after discontinuing ADA was 0.1 in patients who kept in DAS28 (ESR) < 2.6, and 94.9% (37/39) showed no evidence of radiographic progression (> 0.5 per year of a change in mTSS) at 1 year. CONCLUSIONS: It was possible to maintain DAS28 (ESR) < 2.6 after discontinuation of ADA without functional and radiographic progression and very low DAS28 (ESR) at the discontinuation was associated with successful ADA-free DAS28 (ESR) < 2.6 in patients with RA. TRIAL REGISTRATION: University Hospital Medical Information Network Identifier: UMIN000006669.

Clinical, radiographic and functional effectiveness of tocilizumab for rheumatoid arthritis patients--REACTION 52-week study.

OBJECTIVES: To evaluate the effectiveness and safety of tocilizumab in RA patients in clinical practice. METHODS: We observed 232 consecutive RA patients who began tocilizumab in three rheumatology centres in Japan for 52 weeks. Clinical, radiographic and functional status and safety were evaluated. RESULTS: Mean age of the 232 patients was 59.1 years, mean duration of disease was 12.4 years and average DAS using the 28-joint count (DAS-28) was 5.6. Although 62.8% of the patients had been treated previously with anti-TNF biologics, clinical remission at Week 52 was achieved in 43.7%, radiographic non-progression in 62.8% and functional remission in 26.4%. Retention rate at Week 52 was 71.1%, and the same for those with or without previous anti-TNF treatment. Adverse drug reactions leading to tocilizumab discontinuation were observed in 15.5% of patients, the most frequent adverse drug reaction being pneumonia in eight cases. On multivariate logistic regression analysis, DAS-28, HAQ-disability index (HAQ-DI), concomitant MTX and concomitant glucocorticoids (GCs) were predictive variables for clinical remission at Week 52 of tocilizumab treatment. In particular, HAQ-DI was found to be a predictive variable for remission of all three types-clinical, radiographic and functional-at Week 52 of tocilizumab treatment. CONCLUSIONS: In daily clinical practice, tocilizumab exhibited excellent effectiveness in established RA patients, some of whom had failed to respond to previous anti-TNF treatment. Although further detailed safety findings are required, this study provides valuable real-world findings on the management of RA with tocilizumab.

Phenotypic changes of lymphocytes in patients with systemic lupus erythematosus who are in longterm remission after B cell depletion therapy with rituximab.

OBJECTIVE: Rituximab has recently emerged as a novel treatment strategy for systemic lupus erythematosus (SLE). We investigated longitudinally the differentiation and phenotypic changes of peripheral B cells and T cells in patients with SLE after rituximab treatment. METHODS: Phenotypic changes on B cells and T cells in 10 patients with SLE treated with rituximab were analyzed before, 28 days after, and 2 years after rituximab treatment, and at relapse. RESULTS: Rituximab rapidly depleted naive and memory B cells from the peripheral blood. In the patients with prolonged remission, the memory B cells remained depleted while naive B cells recovered within 3-9 months, and the expression levels of CD40 and CD80 remained downregulated for 2 years. There was also a decrease of memory T cells relative to naive T cells, and the expression of CD40L and inducible costimulator (ICOS) on CD4-positive T cells rapidly decreased and remained downregulated for 2 years. In 1 patient, an increase in the number of memory B cells with upregulation of CD40 and CD80 expression was noted just before relapse. In another patient with relapse, however, recovery of CD4-positive memory T cells with upregulation of ICOS expression was noted, with no change in the number of memory B cells. CONCLUSION: Our results suggest that the phenotypic changes of peripheral B cells result in inhibition of T cell differentiation and activation mediated by B cells and thereby bring about longterm remission of SLE. Activated memory B cells or ICOS-positive CD4-positive memory T cells reappeared in association with relapse, probably reflecting the heterogeneity of SLE.

Efficacy of combination therapy of anti-TNF-α antibody infliximab and methotrexate in refractory entero-Behçet's disease.

It is often difficult to manage refractory gastrointestinal tract complications of Behçet's disease (entero-BD) by conventional therapy. In this study, we assessed the short- and long-term efficacy and safety of the combination therapy of infliximab, an anti-tumor-necrosis-factor (TNF)-α antibody, and methotrexate in ten patients with refractory entero-BD refractory to conventional therapies. The short- (weeks) and long-term (by 2 years) effects of infliximab at 3-5 mg/kg body weight every 8 weeks on the clinical course and intestinal manifestations were assessed by abdominal computed tomography (CT) and colonoscopy. The primary endpoint was the rate of disappearance of ileocecal ulceration at 12 months of therapy. All patients showed improvement of gastrointestinal symptoms and disease-associated complications within 4 weeks. Furthermore, the rate of disappearance of ileocecal ulcerations was 50% (5/10 patients) at 6 months and 90% (9/10 patients) at 12 months, and, therefore 90% of patients were satisfied with the primary endpoint. Furthermore, corticosteroid dose was significantly reduced from 22.0 to 1.8 mg/day at 24 months. No severe adverse effects were observed during the 24 months of follow-up. We provide evidence for the rapid and excellent efficacy of infliximab in patients with refractory entero-BD and that the combination of infliximab and methotrexate brings about long-term alleviation of entero-BD and excellent tolerability.