Faculty Bibliography

OBJECTIVE/UNASSIGNED:To further validate a serum proteomics panel for predicting radiographic (structural) knee OA progression. DESIGN/UNASSIGNED:Serum peptides were targeted by multiple-reaction-monitoring mass spectrometry in the New York University cohort (n ​= ​104). Knee OA progression was defined as joint space narrowing ≥1 in the tibiofemoral compartment of one knee per study participant over a 24-month follow-up. The discriminative ability of an 11-peptide panel was evaluated by multivariable logistic regression and area under the receiver operating characteristic curve (AUC), without and with demographic characteristics of age, sex, and body mass index. The association of each peptide with OA progression was assessed by odds ratios (OR) in multivariable logistic regression models adjusted for demographics. RESULTS/UNASSIGNED:The cohort included 46 (44%) knee OA progressors. The panel of 11 peptides alone yielded AUC ​= ​0.66 (95% CI [0.55, 0.77]) for discriminating progressors from non-progressors; demographic traits alone yielded AUC ​= ​0.66 (95% CI [0.55, 0.77]). Together the 11 peptides and demographics yielded AUC ​= ​0.72 (95% CI [0.62, 0.83]). CRAC1 had the highest odds for predicting OA progression (OR 2.014, 95% CI [0.996, 4.296], p ​= ​0.058). CONCLUSIONS/UNASSIGNED:We evaluated a parsimonious serum proteomic panel and found it to be a good discriminator of knee radiographic OA progression from non-progression. Since these biomarkers are quantifiable in serum, they could be deployed relatively easily to provide a simple, cost-effective strategy for identifying and monitoring individuals at high risk of knee OA progression.

Monogenic diseases of immune dysregulation should be considered in the evaluation of children presenting with recurrent neutrophilic dermatoses in association with systemic signs of inflammation, autoimmune disease, hematologic abnormalities, and opportunistic or recurrent infections. We report the case of a 2-year-old boy presenting with a neutrophilic dermatosis, found to have a novel likely pathogenic germline variant of the IKAROS Family Zinc Finger 1 (IKZF1) gene; the mutation likely results in a loss of function dimerization defective protein based on reports and studies of similar variants. IKZF1 variants could potentially lead to aberrant neutrophil chemotaxis and development of neutrophilic dermatoses. Long-term surveillance is required to monitor the development of hematologic malignancy, autoimmunity, immunodeficiency, and infection in patients with pathogenic IKZF1 germline variants.

BACKGROUND:Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. METHODS:Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. RESULTS: = 2.61 [95%CI = 0.93-7.33]; p = 0.069). CONCLUSIONS:CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.

BACKGROUND:For psoriatic patients who need to receive non-live or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE:To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving non-live or live vaccines. METHODS:Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS:Key recommendations include continuing most oral and biologic therapies without modification for patients receiving non-live vaccines; consider interruption of methotrexate for non-live vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS/CONCLUSIONS:Studies regarding infection rates after vaccination are lacking. CONCLUSION/CONCLUSIONS:Interruption of anti-psoriatic oral and biologic therapies is generally not necessary for patients receiving non-live vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

OBJECTIVE:Individuals of racially and ethnically diverse backgrounds are underrepresented in psoriatic arthritis (PsA) research/clinical trials, despite evidence that their disease presentation, severity and course may be distinct. Here we aim to describe how race, ethnicity and other socioeconomic factors inform disease characteristics in PsA. METHODS:817 consecutive patients with PsA from a large, diverse metropolitan area, were enrolled in an observational, longitudinal registry. Demographics, medical history, medication use, and psoriatic disease phenotype and activity were all recorded and analyzed. RESULTS:The population was 77.4% non-Hispanic White, 2.2% Black, 7.1% Asian, and 9.9% identified as other races or multiracial, and 11.8% identified as Hispanic. Hispanic and non-White individuals had higher tender joint counts (p= 0.033) with similar swollen joint counts (p= 0.308) and medication use (p= 0.171). They also had high rates of radiographic axial disease. Hispanic individuals were significantly more likely to have higher tender joint counts (p= 0.029), higher RAPID3 scores (p= 0.004), and moderate-severe psoriasis (p= 0.010) compared with non-Hispanic White individuals. CONCLUSION/CONCLUSIONS:In this diverse cohort, 22.6% of patients identified as underrepresented racial and/or ethnic groups, mostly Asian or Hispanic. Despite similar swollen joint counts and medication use, non-white individuals have higher tender joint counts compared with white individuals. Phenotypically, they also were more likely to have radiographic axial involvement. These findings may reflect differences in PsA presentation, experience and outcomes in individuals of various racial and ethnic groups, which need to be taken into consideration in clinical care and research design.

Raynaud's Phenomenon is a relatively common disease with both primary and secondary forms. It is well understood as a vasospastic condition affecting the acral and digital arteries resulting in characteristic, well-demarcated color changes typically in the hands and feet in response to cold or stress. Secondary RP has been described in association with a variety of rheumatologic and non-rheumatologic diseases, environmental exposures, and/or medications. While both primary and secondary RP may impact quality of life, SRP may lead to permanent and potentially devastating tissue destruction when undiagnosed and untreated. It is therefore crucial for dermatologists to distinguish between primary and secondary disease forms early in clinical evaluation, investigate potential underlaying causes, and risk stratify SRP patients for the development of associated ACTD. The epidemiology, pathogenesis, and clinical presentation and diagnosis of both forms of Raynaud's Phenomenon are described in detail in this review article.

Raynaud's Phenomenon presents with either primary or secondary disease, of which both have the potential to negatively impact patient quality of life. First-line management of RP should include lifestyle modifications in all patients. Some patients with primary RP and most with secondary RP require pharmacologic therapies which may include CCBs, topical nitrates, PDE-5 inhibitors, or endothelin antagonists. Additional approaches to treatment for those with signs of critical ischemia or those who fail pharmacologic therapy include botulinum toxin injection and digital sympathectomy. Herein, we describe in detail the treatment options for patients with RP, as well as provide treatment algorithms for each RP subtype.

OBJECTIVE:Transparency of disclosure in publication is necessary for readers to be aware of any potential conflicts of interest (PCOIs). Past studies of accuracy of disclosure in rheumatology journals have focused exclusively on clinical practice guidelines and not research works. We assessed discrepancy in reporting PCOIs in clinically oriented manuscripts published in the three top-ranked (by impact factor) US-based general rheumatology journals. METHODS:We reviewed disclosures provided by first, second, and last authors of 50 published clinically oriented articles in each of the three top-ranked general US rheumatology journals. For each author, we extracted payment reports from the Open Payments Database (OPD) related to consulting fees, honoraria, and speaker or faculty compensation. We defined a PCOI as a payment received from a company with an ongoing clinical trial or a medication on the market related to the manuscript's subject matter within the 36 months before the online publication date. We additionally analyzed each author individually to determine whether their reported disclosures matched PCOIs from the OPD. RESULTS:Of 150 articles analyzed, 101 included authors with PCOIs. Ninety-two of these 101 publications (92%) contained inaccurate (non- or under-) disclosures. Among 135 authors with PCOIs, 118 reported inaccurately (87%). All 14 articles that published clinical trial results (and all 23 of their qualifying authors) had disclosure inaccuracies. CONCLUSION/CONCLUSIONS:Inaccurate financial disclosure by authors remains an issue in clinically oriented research studies reported in top rheumatology journals. Improved community education and firmer expectations would permit readers to better assess any possible impact of PCOIs on publications.

INTRODUCTION/BACKGROUND:An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy than biologic monotherapy with respect to efficacy outcomes in these patients. OBJECTIVES/OBJECTIVE:To conduct a network meta-analysis (NMA) comparing biologics by treatment class with and without MTX for treatment of adults with active PsA. METHODS:A systematic literature review (SLR) identified randomised, double-blinded, controlled trials, and a Bayesian NMA compared biologics with and without MTX by treatment class (tumour necrosis factor inhibitors (TNFi), interleukin-23 inhibitors (IL-23i) and IL-17i). Efficacy outcomes included American College of Rheumatology 20%, 50% and 70% (ACR20, ACR50 and ACR70) improvement response. RESULTS:The SLR initially identified 31 studies, of which 17 met feasibility criteria for the NMA by containing the 'without MTX' subgroup. For ACR20 efficacy (the most robust assessment examined), all active treatments were significantly better than placebo. No statistically significant differences were demonstrated between biologic monotherapy (for all classes examined) and biologics in combination with MTX for ACR20/50. IL-17i were comparable to IL-23i, and IL-17i were significantly better than TNFi for ACR20. Although limited by fewer trials, TNFi, IL-23i and IL-17i were not statistically different for ACR50/70. CONCLUSIONS:Concomitant use of MTX and biologics did not improve ACR efficacy outcomes versus biologic monotherapy. MTX does not appear to be necessary as a background therapy when biologics are used for the achievement of ACR20/50 responses in patients with PsA.