|
 |
| Brühl H, et al., Eur J Immunol. 2014 Dec 4. |
| In the model of collagen-induced arthritis, an antibody against mouse CD20 depletes B cells very efficiently but fails to suppress the humoral immune response against collagen and the development of arthritis. In contrast, the antibody against CD79b, and a deglycosylated variant of this antibody, almost completely inhibits the increase in anti-collagen antibodies and the development of arthritis. In mice with established arthritis, only the fully glycosylated antibody against CD79b is effective. Our data show that targeting B cells via CD79b is much more effective than B-cell depletion with anti-CD20 antibodies for therapy of arthritis…. |
 |
|
 |
| Frisell T, et al., Ann Rheum Dis. 2014 Dec 12. pii: annrheumdis-2014-206133. |
In this study, the authors estimated the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial coaggregation is of clinical interest, since not only it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases.
Familial coaggregation was found between RA and every arthritis-related disease studied, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) to osteoarthritis. The familial coaggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, other arthritis-related diseases of relatives conferred little or no additional risk….
|
|
|
 |
| Fischer JA, et al., Arthritis Rheumatol. 2015;67(1):51–62. |
Rheumatoid arthritis therapies based on inhibition of a single cytokine produce clinically meaningful responses in only about half of the treated patients. This study was undertaken to investigate whether combined inhibition of TNF-α and IL-17 has additive or synergistic effects in the suppression of mesenchymal cell activation in vitro and inflammation and tissue destruction in arthritis in vivo.
The authors found that combined blockade of TNF-α and IL-17 was more effective than single blockade in inhibiting cytokine, chemokine, and matrix enzyme responses from human mesenchymal cells and in blocking tissue destruction associated with arthritis, and additionally showed a positive impact on rebalance of bone homeostasis. Bispecific anti-TNF-α/IL-17 antibodies may have superior efficacy in the treatment of arthritis and may overcome the limited therapeutic responses obtained with single cytokine neutralization….
|
|
|
 |
| Wallenius M, et al., Arthritis Rheumatol. 2015;67(1):296–301. |
| Linkage of data from a longitudinal observational study of patients with inflammatory joint disease [the Norwegian Disease-ModifyingAntirheumatic Drug (NOR-DMARD) registry study] and the Medical Birth Registry of Norway (MBRN) enabled comparison of pregnancy outcomes in the partners of men with inflammatory joint disease. Outcomes of pregnancies in which the father was exposed to DMARDs within 12 weeks of conception and those in which the father was never exposed to DMARDs were analyzed separately and compared with the outcomes in reference subjects. A total of 1,796 men with inflammatory joint disease were associated with 2,777 births in the MBRN. In 110 of these births, the father had been exposed to DMARDs within 12 weeks before conception, and in 230 births, the father had never been exposed to DMARDs before conception….. |
|
|
 |
| Marks DJ, et al., Arthritis Care Res (Hoboken). 2015 Jan 20. doi: 10.1002/acr.22552. |
| The authors investigated whether a strategy combining clinical and ultrasound (US) assessment can select individuals with rheumatoid arthritis (RA) for sustained dose reduction of anti-tumor necrosis factor (TNF) therapies. As part of a real-world approach, the patients with RA receiving anti-TNF therapies were reviewed in a dedicated biologics clinic. The patients not taking oral corticosteroids with both DAS28 remission (2.6) and absent synovitis on power Doppler US (PDUS=0) for more than 6 months were invited to reduce their anti-TNF therapy dose by one-third. Between January 2012 and February 2014, a total of 70 patients underwent anti-TNF dose reduction. Combined DAS28 and PDUS remission was maintained by 96% at 3 months, 63% at 6 months, 37% at 9 months and 34% at 18 months of follow-up. However, 88% of patients maintained at least low disease activity (LDA) with DAS28 <3.2 and PDUS ≤1 at 6 months…. |
|
|
 |
| Quartuccio L, et al., Arthritis Care Res (Hoboken). 2015 Jan 7. doi: 10.1002/acr.22534. |
| Rituximab (RTX) is licensed for second-line treatment of rheumatoid arthritis (RA) after first TNF inhibitor failure. Rituximab is generally administered intravenously 1 g2 (day 1 to day 15) and the retreatment is scheduled at the time of clinical relapse (Regimen 1). A more intensive regimen is proposed with a fixed full cycle after 6 months (Regimen 2) if remission is not reached. A cost-effectiveness analysis (CEA) compares these two regimens of RTX administration in longstanding RA patients based on data provided by an observational study. Results for the overall sample show at 10-20-30 year that Regimen 1 is less costly and associated with a higher QoL compared to Regimen 2…. |
|
|
 |
| Bliddal H, et al., Evid Based Complement Alternat Med. 2014;2014:269431. |
| The study objective was to investigate the efficacy of ‘energy/spiritual healing’ in rheumatoid arthritis (RA). Eligible patients were women with RA on stable medication. The design was a randomized, blinded, sham-controlled trial; the third group included an external unblinded control of the natural course of RA. Participants in both groups received eight sessions with ‘perceived healing’ over 21 weeks with 8 weeks of follow-up. Active healing (AH) treatment comprised healing with no physical contact, and sham healing (SH) included exactly the same healing with a sham healer. During intervention, participants wore hearing protectors and were blindfolded. No healing (NH) only had their outcomes assessed. Coprimary outcomes were disease activity score (DAS) for 28 joints and Doppler ultrasound. Eighty-two (85%) participants completed the 29-week trial. At end point (week 29), mean difference in DAS28 between AH vs. SH was statistically but not clinically significant in favor of AH, whereas no differences between groups occurred in Doppler ultrasound….. |
|
|
 |
| Mease P, et al., Arthritis Rheumatol. 2014 Dec 29. doi: 10.1002/art.39008. |
| The spondyloarthritides are a group of inflammatory rheumatic diseases characterized by peripheral as well as axial arthritis, radiological sacroiliitis, mucosal and skin inflammation, tendency for familial aggregation and absence of rheumatoid factors and rheumatoid nodules. Numerous studies have established the efficacy and safety of TNF inhibitors (TNFi) in axial SpA and psoriatic arthritis (PsA). Randomized controlled studies on peripheral non-psoriatic SpA have not been conducted. The current study demonstrates that adalimumab is efficacious for peripheral non-psoriatic SpA. A novel outcome measure called the PSpARC 40 was developed for this trial. This outcome measure seems to have face and content validity, but needs further validation….. |
|
|
 |
| Robinson PC, et al., Arthritis Rheumatol. 2015;67(1):140–151. |
| This study demonstrates that there are overlapping but also distinct genetic susceptibility loci for acute anterior uveitis (AAU) and ankylosing spondylitis (AS), and is a step forward in understanding the pathogenesis of AAU. Using the immunochip, the authors compared patients with AS who had AAU to those without AAU. Acute anterior uveitis patients were also compared to healthy controls. Genetic associations that were identified by comparing AS patients with AAU and healthy controls who were not identified previously in AS were deemed to be AAU-specific associations. Loci not previously associated with AS such as IL10-IL19, IL18R1-IL1R1, IL6R, KIF21B, EYS may be important in the pathogenesis of AAU and needs further investigation… |
|
|
 |
| Vogelzang EH, et al., Ann Rheum Dis. 2014;73(12):2178–2182. |
| The phenomenon and adverse consequences of antidrug antibodies (ADA) have been well described in the context of infliximab, a chimeric protein. Similar phenomenon has also been described with the fully human adalimumab in RA. In this prospective study, the authors showed that adalimumab blood levels were lower and disease activity was higher in the presence of ADA to adalimumab. Concomitant MTX lowers the likelihood of developing ADA. Hence, if tolerated, adalimumab is best prescribed in combination with MTX when treating PsA…. |
|
|
 |
| Ramiro S, et al., Ann Rheum Dis. 2015;74(1):52–59. |
| A few long-term studies on radiographic progression in AS are available. Using the OASIS cohort, most of whom have not been exposed to biologic therapy, the authors showed that there is a wide variation in syndesmophyte formation in patients with AS. Syndesmophyte formation was largely unpredictable, alternating with periods of acceleration and quiescence, and may occur in early as well as in very advanced AS. Overall, about 60% of patients will develop at least one syndesmophyte over a 12-year period. HLA B27+ men with syndesmophytes at baseline have the highest progression rates. This study will help in properly designing studies to identify biomarkers for patients with severe AS…. |
|
|
 |
| Kavanaugh A, et al., J Rheumatol. 2015 Jan 15. pii: jrheum.140647. |
In this study, the authors evaluated the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, over 52 weeks in patients with active psoriatic arthritis (PsA) despite prior treatment.
Patients were randomized to placebo (n=168), apremilast 20 mg BID (n=168), or apremilast 30 mg BID (n=168). An American College of Rheumatology 20 (ACR20) response at week 16 was attained by significantly more patients receiving apremilast 20 mg BID (30.4%, p=0.0166) or 30 mg BID (38.1%, p=0.0001) than placebo (19%). Among patients receiving apremilast continuously for 52 weeks (n=254), ACR20 response at week 52 was observed in 63% (75/119, 20 mg BID) and 54.6% (71/130, 30 mg BID) of patients…
|
|
|
 |
| Ogdie A, et al., Ann Rheum Dis. 2015;74(2):326–332. |
In this study, the authors aimed to quantify the risk of major adverse cardiovascular events (MACEs) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis without known PsA compared with the general population after adjusting for traditional cardiovascular risk factors.
A population-based longitudinal cohort study was performed in The Health Improvement Network (THIN) from 1994 to 2010, a primary care medical record database in the UK. Patients with PsA (N=8706), RA (N=41,752), psoriasis (N=138,424) and unexposed controls (N=81,573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in patients with PsA not prescribed a DMARD, patients with RA, patients with psoriasis not prescribed a DMARD and patients with severe psoriasis…. |
|
|
 |
| Husain-Krautter S, et al., 2015 Jan 5. pii: S1521-6616(14)00288-5. |
| Osteopontin or osteoprotegerin (OPG) is a phosphorylated sialoprotein that is present in the extracellular matrix of bones and teeth. Apart from bone homeostasis, it has a prominent role in cell signaling and attachment and hence in immunological responses. The investigators have come out with a new animal model for Sjögren’s syndrome—OPG transgenic mice that show both laboratory and clinical features of the disease. It would be interesting to look at the role of this cytokine in SS and whether we would have a new therapeutic target… |
|
|
 |
| Park JH, et al., J Neurol Sci. 2014 Nov 20. |
| A subset of Sjögren’s syndrome patients presented with features consistent with neuromyelitis optica (NMO). We have observed that most of them are anti-Ro-positive. In this study, the investigators have looked at the prevalence of both anti-Ro antibodies and anti-aquaporin-4 antibodies in the NMOSD (NMO spectrum disorders). Almost all patients with NMOSD who were anti-Ro-positive were also anti-aquaporin-4-positive. What would be the role of immunosuppression, especially rituximab, in these antibody-positive subsets of patients (there is already some data for the same) and how long to give it would be pertinent questions. … |
|
|
 |
| Rodríguez-Castellanos M, et al., Arthritis Res Ther. 2014 Dec 23;16(6):510. |
| The objective of this study was to determine the effectiveness and safety of 8% pirfenidone gel in patients with localized scleroderma. This was an open-label, phase II clinical trial that included 12 patients. Treatment with pirfenidone was indicated, three times a day for 6 months. The patients were evaluated clinically with the modified Localized Scleroderma Skin Severity Index (mLoSSI), as well as with a durometer and histologically using hematoxylin–eosin and Masson’s trichrome stains. We observed histopathological improvement with respect to epidermal atrophy, inflammation, dermal or adipose tissue fibrosis, and annex atrophy. The 8% pirfenidone gel application was well-tolerated and no side-effects were detected…. |
|
|
 |
| Mok CC, et al., Ann Rheum Dis. 2014 Dec 30. |
This was an open-label, randomized controlled parallel group study conducted to compare the efficacy of tacrolimus (TAC) and mycophenolate mofetil (MMF) for the initial therapy of lupus nephritis (LN).
One hundred and fifty adult patients with biopsy-confirmed active LN (class III/IV/V) were randomized to receive prednisolone (0.6 mg/kg/day for 6 weeks and tapered) in combination with either TAC (0.06–0.1 mg/kg/day) or MMF (2–3 g/day) for 6 months. Good responders were shifted to azathioprine for maintenance. The primary outcome was the rate of complete renal response (CR) at 6 months and the secondary outcomes included partial renal response, renal flares and decline of renal function over time.
At month 6, the rate of CR was 59% in the MMF group and 62% in the TAC group [treatment difference: 3% (–12%, 18%); p=0.71]. Maintenance therapy with azathioprine was given to 79% of patients. After 60.8±26 months, proteinuric and nephritic renal flares developed in 24% and 18% of patients in the MMF group and 35% (p=0.12) and 27% (p=0.21) in the TAC group, respectively....
|
|
|
 |
| Joo YB, et al., Int J Rheum Dis. 2014 Dec 19. |
This study was conducted to describe the clinical manifestations, disease activity and organ damage in Korean patients with systemic lupus erythematosus (SLE).
A total of 996 SLE patients were analyzed. The common accrual of ACR criteria included: immunologic (93%), hematologic (93%), arthritic (66%) and nephritic (50%). In the inception cohort over 10 years of follow-up (n=120), the number of ACR criteria increased significantly (5.0±1.2 to 5.7±1.3), and nephritis, serositis and neuropsychiatric symptoms tended to increase continuously over time. SLEDAI-2K decreased significantly (5.6±3.4 to 4.1±1.2), but the percentage of patients with SLEDAI scores ≥12 did not decrease over time.
|
|
|
 |
| Tateyama M, et al., BMJ Open. 2015 Jan 12;5(1):e006763. |
| This is the first study that comprehensively investigated the usefulness of [18F] fluorodeoxyglucose positron emission tomography (FDG PET) in evaluating muscle lesions in patients with polymyositis dermatomyositis syndromes using visual evaluation and standardised uptake value measurement. The study demonstrated the usefulness of these two methods. Visual evaluation of FDG uptake can be used in clinical practice…. |
|
|
 |
| Langdahl BL, et al., J Clin Endocrinol Metab. 2015 Jan 21:jc20144079. |
| In this study, the authors evaluated denosumab therapy in men with low BMD. This was a phase III multicentre study with two treatment periods: a previously reported 12-month, double-blind, placebo-controlled phase and a 12-month open-label phase. A total of 228 men entered the open-label phase and 219 completed the study. Men from the original denosumab (long-term) and placebo (crossover) groups received denosumab 60 mg SC every 6 months. Main outcome measures were BMD, serum C-telopeptide (sCTX), and safety. During the open-label phase, continuous increase in BMD occurs with long-term denosumab treatment. The crossover group showed BMD gains after 12 months of denosumab treatment similar to the long-term denosumab group during the first treatment year. Significant reductions in sCTX were observed following denosumab administration. Adverse event rates were similar between groups and no new safety signals were identified…. |
|
|
|
 |
|
 |
|
