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PURPOSE OF REVIEW: Therapies for rheumatoid arthritis (RA) continue to expand rapidly. The purpose of this review is to discuss novel treatment options, including biosimilars, that are available, as well as to highlight promising agents in development. The purpose is also to discuss new emerging safety signals associated with these drugs and to discuss strategies in tapering therapy. RECENT FINDINGS: There are several novel RA therapies. These include the interleukin 6 receptor blocker sarilumab, which was approved in 2017. In aggregate, the sarilumab studies show that it is effective in RA, including patients with incomplete responses to methotrexate and anti-tumor necrosis factor inhibitor, showing superior efficacy when used in higher dose (200 mg every two weeks) to standard-dose adalilumab. The two biosimilar drugs currently approved are CT-P13 and SB2, which are based on the reference product infliximab. Other drugs that are currently being studied include the interleukin-6 cytokine blocker sarikumab, the small targeted molecule filgotinib, and many new biosimilars. Baracitinib failed to achieve approval by the FDA primarily over perceived safety concerns. Although this review summarizes trials examining biologic tapering, additional data is needed to guide clinicians in regards to treatment de-escalation in RA. SUMMARY: With the greatly expanded armamentarium of RA treatment options available, it is important for clinicians to understand the data regarding drug efficacy and safety. With remission increasingly attainable, effective drug tapering strategies are needed. While tapering trials do exist, more studies will be needed to help guide clinical practice.

This article reviews recent literature on the origin and pathogenic role of anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA).ACPAs and ACPA-immune complexes interact with immune cells to facilitate articular inflammation. Findings from recent in vitro and in vivo studies are congruent with epidemiologic observations in RA supporting a pathogenic role of ACPAs.ACPAs target proteins/peptides with citrullinated epitopes and serve as informative RA biomarkers. ACPAs are generated within synovium and possibly at extra-articular sites prior to disease onset. Proximate to RA onset, critical qualitative and quantitative changes to ACPAs occur that drive proinflammatory responses. Unable to induce arthritis alone, the administration of ACPAs enhances the development and severity of inflammation in mice when a mild synovitis is already present. In vitro studies have elucidated several possible mechanisms linking ACPA to disease progression including: first, activation of inflammatory cells by ACPA-immune complexes; second, ACPA-mediated neutrophil cell death producing neutrophil extracellular traps, which drives inflammation and autoimmunity by releasing citrullinated autoantigen; and finally, direct binding of ACPAs to osteoclasts and resulting osteoclastogenesis. Together, these recent investigations have begun to elucidate the different mechanisms by which ACPAs may be directly pathogenic in RA.

Background: CVD is accelerated in RA, and risk of CVD death is 50% higher in RA patients. Physical activity (PA) mitigates increased CVD risk, but RA patients typically have less PA. It is not known whether PA declines prior to RA onset, or whether joint symptoms (sxs) contribute to PA decline. We sought to determine whether RA-related joint sxs were associated with PA over time in first-degree relatives (FDRs) of RA patients, a population at increased risk for future RA. Methods: In the Studies of the Etiology of RA (SERA), we evaluated associations between presence of joint sxs and hours of PA in 878 FDRs; of whom, 376 had ≥2 visits. A physician confirmed joint swelling; participants self-reported stiffness and pain in the wrist, elbow, or any MCP, PIP, or MTP joints. Hours sleeping, sitting, and performing slight, moderate, or heavy activity during a typical 24-hour day were obtained through questionnaire, weighted to reflect metabolic expenditure, and calculated as follows: PA = (1.0*h sleep + 1.1*h sedentary + 1.5*h slight + 2.4*h moderate + 5.0*h heavy ). Linear mixed models were used to evaluate associations between joint sxs and change in PA over time, adjusting for age, sex, race, BMI, smoking, and positivity for RA-related autoantibodies Results: Mean baseline age was 50±16 years. 74% were female, 78% were White, 7% had joint swelling, 15% had joint stiffness, and 24% had joint pain. Average PA was 37±7. At baseline, PA was higher in FDRs with joint stiffness (B=1.27±0.64, p=0.05) and joint pain (B=1.43±0.54, p=0.01), and lower in FDRs with joint swelling (B=-1.50±0.91, p=0.10). Adjusting for baseline PA, baseline joint swelling, stiffness, and pain were not significantly associated with changes in PA. However, change in joint swelling was associated with increased PA; and changes in joint stiffness and pain were associated with decreased PA. (Table) Conclusion: Joint sxs may not predict future PA, but PA may be lower at the time joint sxs occur. Clinicians should address joint sxs as part of their PA intervention in CVD prevention.

Total shoulder arthroplasties (TSA) are being performed more commonly for treatment of arthritis, although fewer than either hip (THA) or knee (TKA) arthroplasties. Total shoulder arthroplasty also provides general health improvements that are comparable to THA. One study suggests TSAs are associated with lower morbidity and mortality than THAs and TKAs. To confirm and extend that study, we therefore examined the association of patient characteristics (sociodemographics, comorbid illness, and other risk factors) with 30-day complications for patients undergoing TSAs, THAs, or TKAs. We used data from the Veterans Administration (VA) National Surgical Quality Improvement Program (NSQIP) for fiscal years 1999 to 2006. Sociodemographics, comorbidities, health behaviors, operative factors, and complications (mortality, return to the operating room, readmission within 14 days, cardiovascular events, and infections) were available for 10,407 THAs, 23,042 TKAs, and 793 TSAs. Sociodemographic features were comparable among groups. The mean operative time was greater for TSAs (3.0 hours) than for TKAs (2.2 hours) and THAs (2.4 hours). The 30-day mortality rates were 1.2%, 1.1%, and 0.4% for THAs, TKAs, and TSAs, respectively. The corresponding postoperative complication rates were 7.6%, 6.8%, and 2.8%. Adjusting for multiple risk factors, complications, readmissions, and postoperative stays were less for TSAs versus THAs and TKAs. In a VA population, TSAs required more operative time but resulted in shorter stays, fewer complications, and fewer readmissions than THAs and TKAs.

BACKGROUND: Minocycline is recognized as an effective, well-tolerated therapy in rheumatoid arthritis (RA), although its use has been associated with the development of cutaneous hyperpigmentation. OBJECTIVES: To assess the clinical determinants and frequency of minocycline-induced hyperpigmentation in patients with RA. METHODS: A retrospective medical record review of all patients with RA seen in 2 academic rheumatology practices was performed to identify subjects who had received at least 1 month of continuous minocycline therapy. Patient demographics, disease characteristics, medication use, and medication side effects were abstracted from the medical record. Using Cox proportional hazards regression and restricting the analysis to the initial minocycline course, we examined the association of patient factors and concomitant medications with the development of hyperpigmentation. RESULTS: Of 121 patients with at least 1 minocycline course of 30 days or more, 44 (36%) developed documented hyperpigmentation, including 33 during the initial course over a median duration of 9.1 month (range 2.2-77.8 months). Hyperpigmentation was most commonly seen on the upper and lower extremities and the head/neck region. Minocycline-induced hyperpigmentation led to the discontinuation of treatment in 3 patients, with 12 additional patients receiving a dose reduction. Increasing age was the only clinical determinant significantly associated with hyperpigmentation (HR = 1.04; 95% CI 1.00-1.07, P = 0.04). There were no significant associations of sex, weight, concomitant prednisone, or aspirin use with the development of hyperpigmentation. CONCLUSIONS: Minocycline-induced hyperpigmentation is a common complication seen with minocycline use in the treatment of RA, and seems to increase with age.

Although sarcoidosis frequently involves bone, it rarely presents as isolated osseous disease. We present a case in which sarcoidosis is limited to the sacrum and pelvis, a case that underscores the potential importance of both magnetic resonance imaging (MRI) and bone marrow biopsy in establishing the diagnosis. Additionally, we report the interval resolution of bony disease by MRI following glucocorticoid treatment.

Background. The effective use of new steroid-sparing immunosuppressive regimens may lower cumulative glucocorticoid use among renal transplant recipients. However, it is unknown what effect this therapeutic trend has had on bone disease. Methods. Unselected newly transplanted inpatients (n=45) were identified and comprehensively evaluated for metabolic bone disease at a median of 16 days (range 9-33) posttransplant. A follow-up evaluation was conducted a median of 5.7 months (range 4.8-9.3) later. Follow-up values for bone mineral density (BMD) and select laboratories were compared with baseline values using nonparametric statistics. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the associations of baseline characteristics, select laboratory values, and cumulative prednisone and cyclosporine use with spinal BMD loss and were calculated using logistic regression. Results. A significant decrease in intact parathyroid hormone (P

Giant cell arteritis (GCA) is well known for its involvement of the proximal aorta and its branches, classically causing headache, visual impairment, and elevations in the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). We describe a case of biopsy-proven GCA initially presenting with limb claudication, oligoarticular inflammatory arthritis, and a positive antineutrophil cytoplasmic antibody with cytoplasmic staining (C-ANCA), treated successfully with a combination of prednisone and weekly methotrexate. This case illustrates the wide spectrum of features that can be seen with GCA, including the occasional presence of C-ANCA. The C-ANCA became negative after treatment.

Background: Total shoulder arthroplasty is increasingly used in the treatment of arthritis. However, the effect of total shoulder arthroplasty on health-related quality of life has not been fully established. The goal of this systematic review and meta-analysis was to characterize the change in generic and shoulder-specific health-related quality-of-life measures resulting from total shoulder arthroplasty. Methods: We identified published studies reporting preoperative and postoperative health-related quality-of-life outcomes for patients receiving total shoulder arthroplasty. Health-related quality-of-life measures were identified, and meta-analysis was used to calculate standardized mean differences (SMDs, reflective of the effect size) and 95% confidence intervals for each scale. Results: Twenty studies (1576 total shoulder replacements) met the inclusion criteria. Outcome measures were analyzed after an average postoperative follow-up duration of 3.7 ± 2.2 years. The Short Form-36 demonstrated significant improvement in physical component summary scores (SMD = 0.7, p < 0.001) but not in mental component summary scores (SMD = 0.2, p = 0.37). Significant improvements were observed in the visual analog scale score for pain (SMD = −2.5, p < 0.001) and scores on three shoulder-specific measures: the Constant score (SMD = 2.7, p < 0.001), American Shoulder and Elbow Surgeons score (SMD = 2.9, p < 0.001), and Simple Shoulder Test (SMD = 2.3, p < 0.001). Conclusions: Total shoulder arthroplasty leads to significant improvements in scores for function and pain. Shoulder-specific measures of function consistently showed the greatest degree of improvement, with large effect sizes. Total shoulder arthroplasty also leads to significant improvements in overall physical well-being, with a moderate-to-large effect size. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The online version of the original article can be found under doi:10.1007/s11999-009-0996-2.E. V. Fehringer, T. R. Mikuls, K. D. Michaud, J. R. O’DellNebraska Arthritis Outcome Research Center (NAORC),Omaha, NE, USAW. G. HendersonUniversity of Colorado Health Outcomes Program UCD, AMC,Denver, CO, USAW. G. HendersonDenver VA Medical Center, Denver, CO, USAE. V. Fehringer (&)Department of Orthopaedic Surgery and Rehabilitation,University of Nebraska Medical Center, 981080 NebraskaMedical Center, Omaha, NE 68198-1080, USAe-mail: evfehringer@unmc.edu