OBJECTIVE:

The relationship between osteoarthritis (OA) and osteoporosis (OP) remains controversial. An inverse relationship between spine OA and the presence of prevalent vertebral fractures has been shown in osteoporotic women. Our objective was to assess this relationship in osteoporotic men.

METHODS:

All the patients had OP based on densitometric data and were aged ≥ 65 years. Spine radiographs were performed according to a standardized procedure. Vertebral fractures were assessed from T4 to L4 by a semiquantitative method. Disc degenerative changes were assessed by the presence and severity of osteophytes and disc narrowing at levels T12-L1 to L5-S1. Logistic regression was used to study the relationship between the presence of vertebral fracture and lumbar disc degeneration.

RESULTS:

The study included 261 osteoporotic men. The prevalence of vertebral fractures was 26.4% (69/261). At least 1 osteophyte was found in 91.6% (239/261) of patients, and at least 1 disc space narrowing in 63.5% (165/260). The prevalence of at least 1 osteophyte and/or at least 1 disc space narrowing was similar in patients with and those without vertebral fracture. No relationship was found between the presence and/or the severity of osteophytes and disc narrowings and the presence of prevalent vertebral radiographic fractures.

CONCLUSION:

In osteoporotic men, the prevalence of lumbar spine degeneration is high. There is no relationship between lumbar disc degeneration and the presence of vertebral fracture in osteoporotic men.

OBJECTIVE:

Previous studies suggested a role for the death decoy receptor 3 (DcR3) in the pathogenesis of adult systemic lupus erythematosus (SLE). We investigated the role of DcR3 in juvenile-onset SLE, to identify polymorphisms that might alter the function of this protein.

METHODS:

DcR3 was measured in the serum of 61 patients with juvenile SLE. The coding region of the DcR3 gene was sequenced in 100 juvenile and 103 adult patients with SLE, together with 500 healthy controls.

RESULTS:

DcR3 was elevated in the serum of juvenile patients with active SLE disease (440.8 ± 169.1 pg/ml), compared to patients with inactive disease (122.6 ± 28.05 pg/ml; p = 0.0014) and controls (69.27 ± 20.23 pg/ml; p = 0.0009). DNA sequencing identified 2 novel missense mutations: c.C167T (p.T56I) in an adult SLE patient and c.C364T (p.H122Y) in a juvenile patient. Recombinant proteins containing these mutations exhibited altered binding kinetics to FasL and they significantly increased lymphocyte proliferation, compared to the wild-type protein (p < 0.05). The adult patient with SLE carrying the p.T56I mutation had significantly increased lymphocyte proliferation compared to 3 SLE controls matched for age, sex, and disease severity.

CONCLUSION:

DcR3 may play an etiologic role in SLE through either elevated serum levels of wild-type DcR3 or normal levels of gain-of-function DcR3 proteins that increase lymphocyte proliferation.

OBJECTIVE:

To compare Doppler ultrasound (US) and 3.0-Tesla magnetic resonance imaging (3.0-T MRI) findings of synovial inflammation in the tendons and joints in an early polyarthritis cohort (patients who presented < 1 year after arthritis onset) using a bilateral hand and wrist evaluation. Also, to evaluate the diagnostic performance of US and MRI findings for rheumatoid arthritis (RA), their ability to predict RA as a diagnostic outcome, and their capacity to improve the accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria in early arthritis.

METHODS:

Forty-five patients (40 women, 5 men; mean age 45.6 yrs) with untreated recent-onset polyarthritis participated in this prospective study and were examined using an US and MRI approach including both wrists and hands. After a followup of 12 months, patients were classified as having RA if they fulfilled the criteria for RA. The proportion of synovitis identified by US and MRI for each joint and tendon region was compared by chi-square test. The diagnostic performance of US and MRI for RA identification was evaluated using receiver-operating curve (ROC) analysis. Possible associations between synovitis for each joint and tendon region as identified by US or MRI and RA diagnosis at 12 months were tested by logistic regression analysis. The diagnostic perform - ance of the ACR/EULAR RA classification criteria corrected by US and MRI joint and tendon counts was evaluated using ROC analysis.

RESULTS:

Thirty patients fulfilled the ACR/EULAR criteria [early RA (ERA) patients] and the remaining 15 failed to meet these criteria (non-RA). Carpal joint synovitis and tenosynovitis of the flexor tendons was found in 86.7% and 86.7% of patients with ERA on MRI compared with 63.3% and 50% on US, respectively (p < 0.05). The global MRI and US counts revealed a good diagnostic performance for RA diagnosis of both techniques, although MRI was statistically significantly better [area under the curve (AUC) = 0.959 and AUC = 0.853, respectively; z statistic = 2.210, p < 0.05]. MRI identification of carpal joint synovitis (OR 3.64, 95% CI 1.119-11.841), tenosynovitis of the flexor tendons (OR 5.09, 95% CI 1.620-16.051), and global joint and tendon count (OR 2.77, 95% CI 1.249-6.139) were in the multivariate logistic regression model the most powerful predictors of progression toward RA. In the group of ERA patients with US joint and tendon counts ≤ 10, a statistically significant difference was found between the diagnostic performance for RA of the ACR/EULAR criteria as previously described and the diagnostic performance of the MRI-corrected ACR/EULAR criteria (AUC = 0.898 and AUC = 0.986, respectively; z statistic = 2.181, p < 0.05).

CONCLUSION:

3.0-T MRI identified a higher prevalence of synovitis in comparison to US in an early polyarthritis cohort. Both techniques have good diagnostic performance for RA although MRI reveals a significantly higher diagnostic capability. Synovitis of carpal joints and of flexor tendons as identified by MRI were the most powerful predictors of progression toward RA. In patients with US joint and tendon counts ≤ 10, MRI can significantly improve the diagnostic performance of the 2010 ACR/EULAR classification criteria.

OBJECTIVE:

To investigate pregnancy and fetal outcomes in patients with primary Sjögren syndrome (pSS).

METHODS:

An obstetric history of 36 women with established diagnosis of pSS at pregnancy was obtained from a multicenter cohort of 1075 patients. In a subgroup case-control analysis, 12 deliveries in patients with pSS were compared with 96 control deliveries.

RESULTS:

Thirty-six women (31 with anti-SSA/Ro and/or anti-SSB/La antibodies) with an established diagnosis of pSS had 45 pregnancies with the delivery of 40 newborns. Two miscarriages, 2 fetal deaths, and 1 induced abortion were recorded. Mean age at the first pregnancy was 33.9 years; mean number of pregnancies was 1.25; 18/40 (45%) cesarean births were delivered; mean pregnancy length was 38.5 weeks (range 32-43), with 6 preterm deliveries. The mean Apgar score at 5 min was 8.9, mean birthweight was 2920 g (range 826-4060 g). Congenital heart block (CHB) occurred in 2/40 (5%) newborns. The reported rate of breastfeeding for at least 1 month was 60.5%. In 4/40 pregnancies (10%) a flare of disease activity was observed within a year from delivery. In the case-control subgroup analysis, 12 deliveries were compared with 96 controls and no significant differences were found.

CONCLUSION:

Patients with pSS can have successful pregnancies, which might be followed by a mild relapse. CHB was the only cause of death for offspring of mothers with pSS.

OBJECTIVE:

Data on when to stop use of biological agents in rheumatoid arthritis (RA) are scant. We assessed the length of remission and the rate of clinical relapse in patients with RA who had to discontinue treatment with tocilizumab (TCZ) because of the ending of longterm (5 yrs) open-label clinical trials.

METHODS:

All patients at 2 participating centers in Mexico were in remission, defined as Disease Activity Score 28 ≤ 2.6, with no swollen joints at the time of the last TCZ infusion. Patients were followed thereafter every 8 weeks for 12 months or until relapse. Relapse was defined as the presence of ≥ 1 swollen joint. Doses of methotrexate and antiinflammatory drugs were not changed during the followup period.

RESULTS:

Forty-five patients were analyzed, 87% were women (mean age 52 yrs, mean disease duration 14 yrs). During the 12 months of followup, 44% of patients maintained remission. Relapses occurred in 56% of patients: 14 during the first 3 months after the last TCZ administration. Retreatment using other agents achieved low disease activity or remission.

CONCLUSION:

Longterm clinical remission is possible in a number of patients with RA after suspension of TCZ. This effect has also been reported with other biologic agents. Additional data are required to support recommendations for discontinuing a biological agent after achieving remission.

OBJECTIVE:

Clinical remission currently is the treatment target for all patients with rheumatoid arthritis (RA). At the same level of inflammation, the prognosis regarding joint damage is believed to be different for anticitrullinated protein antibody (ACPA)-negative and ACPA-positive patients. Our objective was to show the difference in prognosis at similar disease activity levels, and to illustrate how this could be translated to differentiation of treatment targets.

METHODS:

Data were used from the Nijmegen Early RA Cohort. The relation between the time-averaged disease activity level (by Disease Activity Score; DAS) and joint damage progression over 3 years was analyzed, separately for ACPA-negative and ACPA-positive patients. Joint damage was assessed as change in Ratingen score, and dichotomized as occurrence of erosions in joints that were unaffected at baseline. Linear and logistic multivariable regression models were used.

RESULTS:

The regression coefficient of DAS on change in Ratingen score was 3.9 (p < 0.001) for ACPA-negative and 4.7 (p < 0.001) for ACPA-positive patients, showing less joint damage progression at the same disease activity level in ACPA-negative patients. This difference became greater with increasing disease activity. The probability for erosions in joints unaffected at baseline was 0.35 in ACPA-negative patients when time-averaged DAS was < 2.4 versus 0.80 in ACPA-positive patients.

CONCLUSION:

At the same level of inflammation, ACPA-negative patients have less joint damage and lower probability for damage in newly affected joints than ACPA-positive patients. Low disease activity might be a sufficiently strict treatment target for ACPA-negative patients to prevent progression of joint damage.

OBJECTIVE:

Previous studies indicated that pyridinoline, a collagen crosslink in cartilage and bone, might be a good marker to predict joint destruction in patients with rheumatoid arthritis (RA), although large prospective studies are lacking. We evaluated the predictive value of serum pyridinoline levels for joint destruction, both at baseline for longterm prediction and during the disease course for near-term prediction.

METHODS:

Patients with early RA from the Leiden Early Arthritis Clinic were studied. Radiographs at baseline and yearly during 7 years of followup were scored according to the Sharp-van der Heijde Scoring (SHS) method. Pyridinoline serum levels at baseline and during followup were measured by ELISA. The association between baseline pyridinoline levels and difference in SHS over 7 years was tested, with a multivariate normal regression model. Second, the association between pyridinoline levels determined during the disease course and progression of SHS over the next year was tested with a multivariable linear regression analysis.

RESULTS:

Studying baseline pyridinoline serum levels in 437 patients revealed that the mean SHS over 7 years was 6% higher for every higher pyridinoline level (nmol/l) at baseline (p = 0.001). Subsequently, during followup (n = 184 patients) the progression in SHS in the upcoming year was 17% higher for every higher nmol/l pyridinoline level (p = 0.001). The area under the receiver-operation characteristic curve for rapid radiological progression was 0.59.

CONCLUSION:

Increased pyridinoline serum levels, both at baseline and during the disease course, are associated with more severe joint destruction during the coming year(s), although the predictive accuracy as a sole predictor was moderate.

OBJECTIVE:

To investigate the safety and tolerability of a single subcutaneous (SC) dose of ofatumumab, a fully human anti-CD20 monoclonal antibody, in patients with rheumatoid arthritis (RA) taking background methotrexate (MTX). Secondary objectives included characterizing pharmaco - kinetics and pharmacodynamics.

METHODS:

In this single-blind, phase I/II study, 35 patients with RA were randomized in 5 cohorts to receive a single subcutaneous (SC) ofatumumab dose ranging from 0.3 to 100 mg, or placebo, following premedication with oral acetaminophen and antihistamine. Patients were followed for 24 weeks with extended followup to monitor B cell and immunoglobulin recovery for up to 2 years if required.

RESULTS:

Thirty-five patients received the following treatment: 0.3 mg, n = 4; 3 mg, n = 6; 30 mg, n = 8; 60 mg, n = 6; 100 mg, n = 3; placebo, n = 8. The most common adverse events in the combined ofatumumab groups were headache, nausea, and upper respiratory tract infection. Because of tolerability concerns, only 3 patients were given 100 mg. For the 30-100 mg doses, median maximum plasma concentration values ranged from 4.02 to 4.49 days. Mean elimination half-life values ranged from 5.20 to 6.83 days. Increasing peripheral median B cell depletion was observed from 0.3 mg up to 30 mg, and full target B cell depletion was achieved with 30 mg, 60 mg, and 100 mg.

CONCLUSION:

Treatment of RA patients with SC ofatumumab doses of 30 mg or higher resulted in profound and prolonged B cell depletion in blood. Single doses up to 60 mg were tolerated without glucocorticoid premedication. (ClinicalTrials.gov identifier NCT00686868).