OBJECTIVES:

To evaluate the safety and efficacy of retreatment with tocilizumab (TCZ) in patients who had participated in the DREAM study (Drug free remission/low disease activity after cessation of tocilizumab [Actemar] monotherapy study) and had experienced loss of efficacy.

METHODS:

Patients were retreated with TCZ or other disease modifying antirheumatic drugs (DMARDs). Disease activity was measured using the 28-joint disease activity score (DAS28) for 12 weeks.

RESULTS:

A total of 164 eligible patients, including 161 who experienced loss of efficacy within 52 weeks of the DREAM study, resumed treatment: 157 with TCZ and 7 with DMARDs and/or infliximab. Of TCZ-treated patients, 88.5 % (139 patients) achieved DAS28 <2.6 within 12 weeks, whereas among patients treated with DMARDs and/or infliximab only 14.3 % (1 patient) achieved DAS28 <2.6. Adverse events were observed in 70 TCZ-treated patients (44.0 %), but no serious infusion reactions were observed.

CONCLUSIONS:

Retreatment with TCZ was well-tolerated and effective in patients who had responded to the preceding TCZ monotherapy but had experienced loss of efficacy after cessation of TCZ.

OBJECTIVES:

A post-marketing surveillance (PMS) program was implemented to assess the safety and effectiveness of tacrolimus (TAC) in Japanese rheumatoid arthritis (RA) patients and to identify risk factors related to adverse drug reactions (ADRs).

METHODS:

Patients were registered centrally and monitored for all adverse events (AEs) for 24 weeks. Effectiveness was evaluated using the Disease Activity Score 28-CRP (DAS28-CRP).

RESULTS:

Data from 3,172 patients (mean age 62.2 years) were evaluated in the safety analysis. Of the safety population, 78.5 %were female and 25.9 % were in Steinbrocker's functional class 3 or 4. TAC was prescribed as monotherapy in 52.5 % and the most common concomitant disease modifying antirheumatic drug (DMARD) was methotrexate, used in 28.9 % of the patients. The incidence of AEs, serious AEs (SAEs), ADRs and serious ADRs were 41.2, 6.4, 36.0, and 4.9 %, respectively. The most frequent serious ADR category was infections and infestations. Age ≥65 years, concurrent renal dysfunction, and concurrent diabetes mellitus were identified as significant risk factors for ADR. Based on EULAR response criteria, 65.4 % of the patients showed moderate or good response.

CONCLUSIONS:

The results demonstrate that TAC is well tolerated by Japanese patients with active RA, including those receiving concomitant methotrexate, in the real world.

OBJECTIVE:

Increased femoral neck bone mineral density (BMD) in a hip with osteoarthritis (OA) has been previously reported, however, it is possible that increased BMD at sites other than the hip joint is influenced by the disease process of OA. Therefore, we measured BMD at locations different from the hip joint and determined whether higher BMD was also observed at these different skeletal sites in hip OA patients.

METHODS:

We measured BMD in 68 women (average age 61.0 years) scheduled to undergo total hip arthroplasty for end-stage OA and 100 healthy women (average age 60.9 years) as age-matched controls. BMD at the lumbar spine, radius, and calcaneus was measured by dual-energy X-ray absorptiometry (DXA). Moreover, we measured speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index of the calcaneus by quantitative ultrasonography (QUS).

RESULTS:

BMD obtained by DXA at the lumbar spine and radius was significantly higher in hip OA patients than in controls. However, at the calcaneus, no significant differences were observed between the groups in BMD obtained by DXA. SOS, BUA, and stiffness index obtained by QUS were significantly lower in the OA group than in controls.

CONCLUSION:

Higher BMDs of the spine and radius suggest that the incidence of osteoporosis is inversely associated with the incidence of OA. However, it remains unclear whether lack of difference in BMD and lower SOS, BUA, and stiffness index of the calcaneus in the OA group was secondary to the effect walking disturbance resulting from hip pain. Our data suggest that hip OA patients have higher BMD than healthy women, and that inactivity or immobilization caused by hip OA may reduce BMD in the lower limb.

OBJECTIVES:

To investigate the duration of remission and low disease activity (LDA) after cessation of tocilizumab (TCZ) treatment in rheumatoid arthritis patients who showed remission or LDA as assessed by DAS28 in response to preceding TCZ monotherapy, and to explore the factors contributing to prolonged efficacy duration.

METHODS:

Disease activity was monitored for 56 weeks. The rate of continued efficacy was estimated by Kaplan-Meier curves.

RESULTS:

A total of 187 patients were eligible. At baseline of this study, median disease duration was 7.8 years, preceding TCZ treatment period was 4.0 years and DAS28 was 1.5. The rate of continued LDA at 52 weeks was 13.4 % according to the Kaplan-Meier estimate. 19 patients (10 %) were completely drug-free and 17 patients (9.1 %) fulfilled DAS28 remission at 52 weeks. Multivariate Cox regression analysis identified low serum IL-6 and normalisation of MMP-3 levels at cessation of TCZ as independent predictive markers for longer duration of LDA. In patients with low serum IL-6 (<12.9 pg/mL) and normal MMP-3 levels, the rate of continued LDA reached 38.0 % at 52 weeks.

CONCLUSIONS:

TCZ monotherapy may induce biologics-free remission or LDA without concomitant use of synthetic DMARDs. Serum levels of IL-6 and MMP-3 are useful markers for identifying patients who could discontinue TCZ without acute disease flare.

OBJECTIVES:

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by new bone formation. Recent evidence suggests that new bone formation in AS may be due to upregulation of Wnt signaling in the osteoblastic pathway secondary to low serum Dickkopf homolog 1 (Dkk-1) levels. And miR-29a orchestrates osteoblast differentiation through direct targeting and negative regulation of Dkk-1.

METHODS:

We initially validated the expression levels of miR-29a in the peripheral blood mononuclear cells (PBMCs) of AS patients (n = 30), rheumatoid arthritis (RA) patients (n = 30) and healthy controls (n = 30) using real-time quantitative reverse transcription PCR (qRT-PCR). Correlation analysis was assessed between miR-29a level in PBMCs of AS patients and disease activity indexes, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI) and modified Stoke ankylosing spondylitis spinal score (mSASSS).

RESULTS:

Significantly higher expression of miR-29a was observed in PBMCs of AS patients (Ct 9.18 ± 1.96) compared with that in RA patients (10.97 ± 0.70, p < 0.001) and healthy controls (Ct 11.45 ± 1.23, p < 0.001). There was no significant difference between RA patients and healthy controls in miR-29a expression (p > 0.05). Elevated miR-29a expression is not correlated with disease activity index (p > 0.05). A weak correlation was found between elevated miR-29a expression and mSASSS (r = -0.393, p = 0.032).

CONCLUSIONS:

We report for the first time elevated miR-29a expression in PBMCs of patients with ankylosing spondylitis, and miR-29a might be used as a useful diagnostic marker in new bone formation but cannot reflect disease activity.

OBJECTIVE:

To assess the reliability and sensitivity of a novel scoring method to evaluate the radiographic appearance of and longitudinal changes including joint remodeling in large joints with early and established rheumatoid arthritis (RA).

METHODS:

The ARASHI study group devised new radiographic scoring systems (Status score; range 0-16 points, and Change score; range -11 to 12 points) for evaluation of large joints with RA. Radiographs showing anterior/posterior views of large joints (shoulder, elbow, hip, knee, and ankle joints) taken at two time points (mean interval 2.3 years) were collected from 25 patients with established RA (5 patients for each of the 5 joints, 50 films in total), and an additional 5 films of each joint with severe joint destruction were collected from 5 different sets of RA patients. After consensus on the definition of each component and reader training, images were evaluated using the Larsen's grading system and the ARASHI Status and Change score by 9 independent senior orthopedic surgeons. The reliability was estimated by intra-class correlation coefficients (ICCs) and measurement error by 95 % confidence intervals of minimum detectable change (MDC95).

RESULTS:

ARASHI Status score and Change score significantly correlated with Larsen's grade (r = 0.89, P < 0.0001) and follow-up-baseline differences in Larsen's grade (r = 0.83, P < 0.0001), respectively. Inter-reader ICCs were very high for both Status score (0.88, 95 % confidence interval [CI], 0.83-0.92, P < 0.001) and Change score (0.92, 95 % CI, 0.87-0.96, P < 0.001). Intra-reader ICCs were also very high for both Status score (0.92, 95 % CI, 0.71-0.98, P < 0.001) and Change score (0.97, 95 % CI, 0.91-0.99, P < 0.001). The MDC95 for inter-reader agreement were 4.18 (25 % of maximum obtainable score, MOS) and 4.99 (21 % of MOS) for Status score and Change score, respectively. The MDC95 for intra-reader agreement was acceptable with 2.82 (17 % of MOS) and 3.02 (13 % of MOS) for Status score and Change score, respectively.

CONCLUSION:

The ARASHI scoring method showed good inter-/intra-reader reliability with high ICCs and acceptable MDC95 with respect to each large joint and the components of both Status and Change scores. The results suggest that the ARASHI scoring method might be useful for the assessment of status, as well as longitudinal monitoring of destruction and remodeling of large joints with RA.

OBJECTIVES:

Silica exposure has been associated with an increased risk of developing rheumatoid arthritis (RA), especially among smokers. In this study, we aimed at examining the association between silica exposure (and its interaction with smoking) and the risk of RA in the Malaysian population.

METHODS:

In total, 149 cases and 213 matched controls, all men, were included between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched on sex, age and residential area. Silica exposure was defined as exposure to stone dust, rock drilling or stone crushing, and smoking status was categorized as ever/never cigarette smoking.

RESULTS:

An increased risk of anti-citrullinated protein antibody (ACPA)-positive RA (OR = 2.4, 95 % CI 1.0-5.6) was observed among those exposed to silica. Ever-smokers exposed to silica had a particularly high risk of developing ACPA-positive RA (OR = 7.5, 95 % CI 2.3-24.2), compared with never-smokers not exposed to silica. No association was found regarding ACPA-negative RA.

CONCLUSION:

Our data demonstrate that exposure to both silica and cigarette smoke comprise risks for developing RA in the Malaysian genetic context. The findings expand a link between environmental lung exposures and ACPA-positive RA to Asian populations.

A 68-year-old Japanese male presented with atrophic erythematous white lesions with peripheral dark reddish rims on his back. Multiple ulcers were detected from his stomach to his large intestine using endoscopy. Although the patient was given high doses of a steroid, aspirin, dipyridamole, and intravenous immunoglobulin therapy, he died of gastrointestinal hemorrhage, perforation and septic shock. An autopsy examination revealed pauci-inflammatory thrombotic microangiopathy with endothelial cell injury, fibrous occlusive arteriopathy, and vascular C5b-9 deposition in the wall of the gastrointestinal tract from the esophagus to the large intestine as well as in the dermis of the skin.