ObjectiveThe objective of this study was to ascertain pegloticase persistence and adverse events associated with concomitant immunomodulatory drug treatment in patients with gout.MethodsWe conducted a retrospective analysis of patients with gout using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness registry from January 2016 through June 2020. The first pegloticase infusion defined the index date. Based on concomitant immunomodulatory drug treatment, we identified three exposure groups: (1) immunomodulatory drug initiators (patients initiating an immunomodulatory prescription ±60 days from the index date), (2) prevalent immunomodulatory drug recipients (patients receiving their first immunomodulatory drug prescription >60 days before the index date with at least one prescription within ±60 days of the index date), and (3) immunomodulatory nonrecipients (patients receiving pegloticase without concomitant immunomodulatory drugs). We calculated the proportion of patients who achieved serum urate levels ≤6 mg/dL and who had laboratory abnormalities (white blood cell count <3.4 x 109/L, platelet count <135,000, hematocrit level <30%, alanine aminotransferase or aspartate aminotransferase level ≥1.5 times the upper limit normal value) within 180 days after the index date. Cox regression analyzed time to pegloticase discontinuation, controlling for potential confounders.ResultsWe identified 700 pegloticase recipients (91 immunomodulatory drug initiators, 33 prevalent immunomodulatory drug recipients, and 576 nonrecipients), with a median follow‐up of 14 months. Immunomodulatory drug recipients were less likely to discontinue pegloticase. The adjusted hazard ratios of pegloticase discontinuation associated with concomitant immunomodulatory drug initiation and prevalent treatment were 0.52 (95% confidence interval [CI] 0.37–0.75) and 0.69 (95% CI 0.42–1.16), respectively. Laboratory abnormalities were uncommon (<5%) and were not higher in concomitant immunomodulatory drug treatment.ConclusionConsistent with clinical trials, results from this large observational registry suggest that concomitant immunomodulatory drug treatment improves pegloticase persistence.

Purpose of review Glucocorticoids justifiably remain a cornerstone in the treatment of many inflammatory rheumatic diseases but many are opposed to their use because of the side effects, most of them known to be dose-dependent. Most concerns regarding glucocorticoids stem from observational studies which are affected by several forms of bias, mainly confounding by indication, that may result in overestimation of harm. Solid evidence regarding the safety of low-dose glucocorticoids remains remarkably scarce. Recent findings Several observational studies showed heterogeneous results and two 6-month trials showed no increase of harm. The GLORIA trial of 5 mg/day prednisolone vs. placebo in patients aged 65+ is the first randomized control trial with glucocorticoids safety as coprimary outcome. The benefits of glucocorticoids in terms of symptoms and structural damage were confirmed, but the proportion of patients with at least one adverse event of special interest (serious or glucocorticoids-related) was increased by 24%, mostly due to nonsevere infections. Summary Based on current evidence the benefit–risk balance of low-dose glucocorticoids in rheumatoid arthritis, and probably in other rheumatic diseases is generally favourable. Physicians should be aware of the risks and mitigate them, but avoid the negative effects of unfounded fear.

ObjectiveDisagreement exists between rheumatology and primary care societies regarding gout management. This paper describes a formal process for gathering input from stakeholders in the planning of a trial to compare gout management strategies.MethodsWe recruited patients, nurses, physician assistants, primary care clinicians, and rheumatologists to participate in a modified Delphi panel (mDP) to provide input on design of a trial focused on optimal management for primary care patients with gout. The 16 panelists received a plain‐language briefing document that discussed the rationale for the trial, key clinical issues in gout, and aspects of trial design. The panelists also received information and considerations on nine voting questions (VQs), judged to be the key design questions. Cognitive interviews with panelists ensured that the VQs were understood by the range of panelists involved in the mDP. Panelists were asked to score all VQs from 1 (definitely no) to 9 (definitely yes). Two voting rounds were conducted—round 1 by email and round 2 by video conference.ResultsThe VQs were modified through the cognitive interviews. The round 1 voting resulted in consensus on eight items, with consensus defined as median voting score in the same tercile (1‐3, 4‐6 or 7‐9). Re‐voting at the meeting (round 2) reached consensus on the remaining item.ConclusionAn mDP with various stakeholders facilitated consensus on the design of a trial of different management strategies for chronic gout. This method may be useful for designing trials of clinical questions with substantial disagreement across stakeholders.

The phase 3 teriparatide Fracture Prevention Trial showed significant reductions in vertebral (VF) and nonvertebral (NVF) fractures; however, patient exposure was insufficient for full analysis of low-incidence fractures, including hip. We assessed fracture results in pooled data from four prospective, observational teriparatide studies. Ambulatory women and men with osteoporosis received subcutaneous teriparatide 20 µg/day for up to 24 months per routine clinical practice. Fracture rates were compared between 6-month periods, using 0 to 6 months of treatment as the reference period. Analyses used a piecewise exponential model for first fracture. Hip, NVF, clinical VF (CVF), any clinical, and wrist fractures were assessed. For 8828 patients analyzed, mean age was 71 years; mean (SD) treatment duration was 17.4 (8.6) months. The rate of hip fracture decreased significantly for the > 12 to 18-month (− 47.7%) and > 18-month periods (-85.2%) versus the first 6 months of therapy, and for the > 18 versus the > 6 to 12-month period. NVF, CVF, and all clinical fractures were all significantly decreased in each post-reference period, with maximum decreases (> 18-month period) of 52.7%, 69.4%, and 61.2%, respectively, versus 0 to 6 months. No significant reduction was seen for rates of wrist fracture. Teriparatide treatment was associated with statistically significant decreases in hip fracture rate, particularly for > 18 months of treatment, and in NVF, CVF, and all clinical fracture rate in real-world patients. These results should be interpreted in the context of the non-controlled design of the source studies.

Introduction: Serious infections are an important side effect of immunosuppressive therapy used to treat Crohn's disease (CD) and ulcerative colitis (UC).Recent studies have focused on the impact of specific infections such as C difficile.There have been no nationally representative studies examining the entire spectrum of infection related hospitalizations in patients with IBD.Methods: We identified all adult CD and UC related hospitalizations from the Nationwide Inpatient Sample 2007, the largest all-payer hospitalization database in the United States comprising over 1000 hospitals from 40 states.We then identified all infection-related hospitalizations through codes for either the specific infections or disease processes (sepsis, pneumonia, etc).Overall burden of all infection-related hospitalizations as well as those with infection as the primary reason for hospitalization were estimated.Excess morbidity associated with infections was calculated using multivariate regression models.Results: There were an estimated 67,221 hospitalizations related to infections in patients with IBD, comprising 27.5% of all IBD hospitalizations.Infections were the primary reason for hospitalization in 23,493 patients and accounted for 150,620 days in hospital stay.Infections were associated with 25% of hospitalizations in the age-group 19-35 years, increasing to 33% in patients 66 years and older (OR 1.20, 95% CI 1.11 -1.30).The distribution of infections varied by age group; pneumonia, sepsis, UTI and C difficile were more common in the oldest age group while abdominal or peri-rectal abscess were more common in the younger patients and others such as fungal infections were equal across all age-groups (Figure 1).On multivariate analysis, infections were independently associated with age, comorbidity, malnutrition, TPN, and bowel surgery.Infection-related hospitalizations had a four-fold greater mortality (OR 4.4, 95%CI 3.7-5.2).However, this varied by type of infection with the strongest effect seen for sepsis (OR 15.29,), pneumonia (OR 3.6, 95%CI 2.9-4.5) and C difficile (OR 3.2, 95%CI 2.6-4.0), and weaker effects for UTI (1.4,95%CI 1.1-1.7)or fungal infections (OR 1.5, 95%CI 1.0-2.2).Infections were also associated with an estimated 2.3 days excess hospital stay (95%CI 2.2-2.5) and $12,482 in hospitalization charges.Conclusion: Infections account for significant morbidity and mortality in patients with IBD and disproportionately impact older IBD patients with greater comorbidity.However, spectrum of infections varies by age-group.Pneumonia, sepsis and C difficile are associated with the greatest excess mortality risk.

BACKGROUND:Determining anatomic sites and circumstances under which a fracture may be a consequence of osteoporosis is a topic of ongoing debate and controversy that is important to both clinicians and researchers. METHODS:We conducted a systematic literature review and generated an evidence report on fracture risk based on specific anatomic bone sites and fracture diagnosis codes. Using the Research and Development/University of California at Los Angeles appropriateness process, we convened a multidisciplinary panel of 11 experts who rated fractures according to their likelihood of being because of osteoporosis based on the evidence report. Fracture sites (as determined by International Classification of Diseases Clinical Modification codes) were stratified by four clinical risk factor categories based on age, sex, race/ethnicity (African American and Caucasian), and presence or absence of trauma. RESULTS:Consistent with current clinical experience, the fractures rated most likely because of osteoporosis were the femoral neck, pathologic fractures of the vertebrae, and lumbar and thoracic vertebral fractures. The fractures rated least likely because of osteoporosis were open proximal humerus fractures, skull, and facial bones. The expert panel rated open fractures of the arm (except proximal humerus) and fractures of the tibia/fibula, patella, ribs, and sacrum as being highly likely because of osteoporosis in older Caucasian women but a lower likelihood in younger African American men. CONCLUSION:Osteoporosis attribution scores for all fracture sites were determined by a multidisciplinary expert panel to provide an evidence-based continuum of the likelihood of a fracture being associated with osteoporosis.