No difference in clinical parameters and drug retention in PsA patients receiving b/tsDMARD monotherapy versus combination with methotrexate: data from the RABBIT-SpA registry.

BACKGROUND: The potential benefit of methotrexate (MTX) in combination with biologic (b) and targeted synthetic (ts) disease modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA) is still a matter of debate. OBJECTIVES: To compare clinical and patient reported characteristics as well as drug retention rates in PsA patients receiving b/tsDMARD monotherapy or in combination with MTX. METHODS: RABBIT-SpA is a prospective longitudinal cohort study including axSpA and PsA patients. In this analysis, PsA patients were stratified into two groups: starting b/tsDMARD as monotherapy or in combination with MTX. Treatment retention was compared by drug survival analysis. RESULTS: 69% of the patients (n=900) started b/tsDMARD as monotherapy while 31% were treated in combination with MTX (n=405). At baseline, clinical domains like skin, nail and joint affection, dactylitis, enthesitis and axial involvement were similar between the groups. Only the patients' satisfaction concerning tolerability of the previous treatment was significantly better in the combination group at treatment start. Drug retention rates did not differ between the groups (p=0.4). At 6/12 months, 66%/48% of patients in monotherapy and 67%/48% in the combination group were still on their original treatment. CONCLUSIONS: We did not identify any clinical parameters with notable influence on the choice of b/tsDMARD mono or MTX-combination therapy in PsA. Drug retention rates are similar between mono and combination therapy. It seems that the decision to continue MTX at initiation of b/tsDMARDs is mostly based on the subjective tolerability of MTX treatment.

Effectiveness and safety of a biosimilar-to-biosimilar switch of the TNF inhibitor etanercept in patients with chronic inflammatory rheumatic diseases.

Background: Biosimilar disease-modifying anti-rheumatic drugs (bsDMARDs) has created a financial incentive to encourage switching to cheaper products. Objectives: We aim to study the effectiveness and safety of a non-medical bsDMARD-to-bsDMARD switch from originator etanercept (ETN) to bsDMARD ETN (SB4) and successive to another bsDMARD ETN (GP2015) in patients with chronic inflammatory rheumatic diseases in a real-life setting. Methods: Retrospective chart review of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) who had been treated with originator ETN and were switched twice to ETN bsDMARD for non-medical reasons thereafter. All patients received ETN 50 mg/week. Disease activity and physical function was assessed every 12 weeks with standardized questionnaires. Results: A total of 100 patients who switched twice [54 RA, 27 axSpA, 19 PsA, mean age 54.3 (15.1), 46% male] were included. Patients with axSpA were younger than RA and PsA patients. Patients with SpA were less likely to receive conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than RA patients. Duration of treatment with originator ETN before the first switch was 3.3 (2.3) years. Retention rate 6 months after the second ETN bsDMARD switch was 89%. Disease activity and physical function scores remained rather unchanged in patients with RA and axSpA longitudinally, while there was some more fluctuation in PsA patients. Six patients lost efficacy and were switched back to originator ETN in month 6 (n = 4) or to another mode of action (n = 2). There were 14 adverse events (AE) reported in eight patients. One patient re-administered bsDMARD GP2015 successfully 3 months after healing of mucosal erosions. Conclusion: No relevant change in disease activity and physical function were observed in a non-medical bsDMARD-to-bsDMARD switch scenario. The retention rate after switches from originator ETN to two ETN bsDMARD was close to 90%. Multiple switches resulted in a high adherence rate without clinically important efficacy or safety signals.

Changes of immunosuppressive medication because of COVID-19 by patients with chronic inflammatory rheumatic diseases: anxiety was not a major driver.

OBJECTIVES: To study treatment decisions of patients with chronic inflammatory rheumatic diseases (CIRD) at the beginning of the SARS- CoV-2 pandemic in relation to disease characteristics with focus on anxiety. METHODS: A total of 970 CIRD patients diagnosed with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriasis arthritis (PsA) and connective tissue diseases (CTD), selected from our records who had presented to our hospital at least twice during last year, were contacted by telephone to be asked about medication changes, health status and therapy satisfaction. Standardised tools were used to assess disease activity, anxiety and depression, the latter by Hospital Anxiety and Depression Score (HADS) with a score ≥8 denoting definite anxiety and/or depression. The cut-off for RADAI was set at ≥3.2 and for BASDAI ≥4. Compliance with prevention rules and vaccination status were assessed. RESULTS: Complete interviews of 557 patients (57.4%) made between April and July 2020 were available for analysis. The median age was 55 (47-63), disease duration 9.0 (4.5-17.0) years, 61.9% females. A recent change in medication was reported by 197 patients (35.4%), 51.2% of which admitted that this decision was mainly made due to the pandemic with more changes occurring with bDMARDs (21.8%) than cDMARDs (6.6%) and corticosteroids (5.4%). There was no major difference between patients who changed because of the pandemic or self-reported inactive disease versus patients who did not change therapy regarding disease activity, depression and anxiety (41%, 17.2%, 31.3% vs. 47.5%, 22.5%, 35.0% vs. 48.9%, 27.7%, 34.1%). More than 90% of patients reported that they rigorously followed Corona prevention rules. The majority of patients were vaccinated against influenza (55.3%) and pneumococci (61.3%), respectively. CONCLUSIONS: Anxiety, depression and disease activity did not play an important role in decisions favouring change of therapy, even though many patients changed medication due to the pandemic. Patients probably protected themselves by strictly adhering to hygiene recommendations. Vaccination rates against influenza and pneumococci were better than previously reported, but still too low.

Imaging of diffuse idiopathic skeletal hyperostosis (DISH).

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of ligaments and entheses. The condition usually affects the axial skeleton, in particular, at the thoracic segment, though also other portions of the spine are often involved. DISH often involves also peripheral tendinous and/or entheseal sites either alone, or in association with the involvement of peripheral joints. At times, new bone formation involves the bone itself, but sometimes it involves joints not usually affected by osteoarthritis (OA) which result in bony enlargement of the epiphysis, joints space narrowing and a reduced range of motion. Because of the entheseal involvement, DISH can be mistaken for seronegative spondyloarthropathies or for a "simple" OA. Furthermore, other implications for the recognition of DISH include spinal fractures, difficult intubation and upper endoscopies, decreased response rates in DISH with concomitant spondyloarthritides, and increased likelihood to be affected by metabolic syndrome and cardiovascular diseases. This Atlas is intended to show the imaging finding in DISH in patients diagnosed with the condition by the Resnick classification criteria.

[Dermatomyositis associated with rapid progression of pulmonary involvement]. / Progrediente pulmonale Beteiligung bei amyopathischer Dermatomyositis.

In this case series we present three patients with autoimmune dermatomyositis or polymyositis with rapid-progressive interstitial pulmonary involvement. Despite intensive escalation of the immunosuppressive therapy the patients developed acute respiratory distress syndrome with lethal outcome only a few months after diagnosis. All three patients had increased myositis-specific or myositis-associated antibodies - two patients were detected with anti-melanoma differentiation-associated gene (MDA5) antibodies and the third patient with anti-Ku antibodies. Dermatomyositis and polymyositis are rare autoimmune diseases with variable clinical manifestations and several different antibody constellations. In particular the presence of anti-MDA5 antibodies is associated with progressive pulmonary involvement, complicated progression and poor prognosis.

[Chronic Back Pain, Cervicothoracic Myeolopathy and weight loss - a case report of an IgG4-related disease]. / Chronische Rückenschmerzen, zervikothorakale Myeolopathie und Gewichtsverlust ­ ein Fallbericht über eine IgG4-assoziierte Erkrankung.

HISTORY: A 68-year-old woman presented with chronic back pain, a poor general condition, weight loss of 20 kg in the last 6 months and paretic hands. FINDINGS AND DIAGNOSIS: The patient had pareses of hand- and finger muscles on both sides with corresponding deficits proven by EMG. MRI revealed an intraspinal mass affecting the cervical and thoracic spine with myelon compression. Histologically IgG4-positive plasma cells were detected and IgG4-RD with spinal pseudotumor and resulting cervicothoracic myelopathy were diagnosed. THERAPY AND COURSE: After initiation of high-dose glucocorticoid therapy (100 mg i. v. over 7 days with reduction afterwards) and cyclophosphamide-pulse-therapy (initially 750 mg i. v., cumulative dose of 4500 mg in 6 months), the general condition and motor deficits improved. CONCLUSIONS: The CNS are a rare manifestation of IgG4-RD. The tumor typically grows displacing, is best visualized on MRI or PET-CT, presenting clinically the corresponding pain and neurological deficits and shows characteristic histology. Steroids and, as in our case helpful, advanced immunosuppression can be a promising treatment option.

Diagnoses associated with dietary supplement use in a national dataset.

OBJECTIVES: The purpose of this study was to determine if participant diagnosis, as determined by a health care provider, is associated with dietary supplement (DS) use. DESIGN/SETTING: Surveys from 1255 study participants aged 34-84, part of the Midlife in the US Study (MIDUS 2 Survey) Biomarker Project, were reviewed. Participant data included pharmaceutical use (prescription and over-the-counter medications (OTC)), clinical symptoms and diagnosis, and laboratory results. Associations were calculated between the above participant characteristics and DS use. MAIN OUTCOME MEASURES: Frequency of DS use for physician-reported diagnoses. RESULTS: Overall prevalence of DS use was 32.4%. Participants taking DS were more often female (p = .048), white (p < 0.001), and older (mean age 57 years, p < 0.001). Participants taking DS reported taking more OTC (p < .001) and prescription medications (p = .024), and had an increased number of chronic conditions (p = .004). Participants reporting physician-diagnosed diabetes were significantly less likely to be taking DS (p = .0066), while participants with eye disease (p = .001), high cholesterol (p = 0.041), cancer (p = 0.042), and arthritis (p = 0.044) were more likely to be taking DS than those without those conditions. No difference in DS use was found between patients with and without other identified medical conditions. After adjusting for age, race/ethnicity, and gender, only diabetes remained a significant predictor of decreased DS use (OR 0.588, CI 0.388-0.873, p = .01). CONCLUSIONS: Some physician-reported participant diagnoses were associated, positively or negatively, with DS use.

The Overlap of Dietary Supplement and Pharmaceutical Use in the MIDUS National Study.

Introduction. In the United States, dietary supplement (DS) use is common, often takes place outside of the purview of health care providers, and may involve DS in combination with pharmaceuticals. This situation has led to concerns about interactions between DS and pharmaceuticals, as well as the risks from polypharmacy and polysupplement use. Methods. We used data from the Midlife in the US study (MIDUS 2 Survey) to examine DS and prescription pharmaceutical use in 3876 study participants in order to determine the demographics of high-users (5 or more) of DS and pharmaceuticals and the presence of DS-pharmaceutical co-use. Results. Over 69% of study participants regularly used DS, 49.6% regularly used both DS and pharmaceuticals, and 6.3% and 8.7% were high-users of pharmaceuticals and DS, respectively. High-users of DS, pharmaceuticals, and either were more likely than the whole cohort to be female and of lower income. Conclusions. These findings corroborate those of other national studies with respect to the demographics of DS users but add new information about people at risk of DS-pharmaceutical interactions, not an insignificant proportion of the population examined by this dataset.

Evaluation of 8.0-cm needle at the fourth anterior axillary line for needle chest decompression of tension pneumothorax.

BACKGROUND: Five-centimeter needles at the second intercostal space midclavicular line (2MCL) have high failure rates for decompression of tension pneumothorax. This study evaluates 8-cm needles directed at the fourth intercostal space anterior axillary line (4AAL). METHODS: Retrospective radiographic analysis of 100 consecutive trauma patients 18 years or older from January to September 2011. Measurements of chest wall thickness (CWT) and depth to vital structure (DVS) were obtained at 2MCL and 4AAL. 4AAL measurements were taken based on two angles: closest vital structure and perpendicular to the chest wall. Primary outcome measures were radiographic decompression (RD) (defined as CWT < 80 mm) and radiographic noninjury (RNI) (DVS > 80 mm) of 8-cm needles at 4AAL. Secondary outcome measures are effect of angle of entry on RNI at 4AAL, RD and RNI of 8-cm needles at 2MCL, and comparison of 5-cm needles with 8-cm needles at both locations. RESULTS: Eighty-four percent of the patients were male, with mean Injury Severity Score (ISS) of 17.7 (range, 1.0-66.0) and body mass index of 26.8 (16.5-48.4). Mean CWT at 4AAL ranged from 37.6 mm to 39.9 mm, significantly thinner than mean CWT at 2MCL (43.3-46.7 mm). Eight-centimeter needle RD was more than 96% at both 4AAL and 2MCL. Five-centimeter RD ranged from 66% to 81% at all sites. Mean DVS at 4AAL ranged from 91.8 mm to 128.0 mm. RNI at all sites was more than 91% except at left 4AAL, when taken to the closest vital structure (mean DVS, 91.8 mm), with 68% RNI. Perpendicular entry increased DVS to 109.4 mm and subsequent RNI to 91%. Five-centimeter RNI at all sites was more than 99%. CONCLUSION: CWT at 4AAL is significantly thinner than 2MCL. Based on radiographic measurements, 8-cm catheters have a higher chance of pleural decompression when compared with 5-cm catheters. Steeper angle of entry at 4AAL improves 8-cm noninjury rates to more than 91%. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV.

Panax ginseng.

The herbal remedies referred to as "ginseng" are derived from the roots of several plants. One of the most commonly used and researched of the ginsengs is Panax ginseng, also called Asian or Korean ginseng. The main active components of Panax ginseng are ginsenosides, which have been shown to have a variety of beneficial effects, including anti-inflammatory, antioxidant, and anticancer effects. Results of clinical research studies demonstrate that Panax ginseng may improve psychologic function, immune function, and conditions associated with diabetes. Overall, Panax ginseng appears to be well tolerated, although caution is advised about concomitant use with some pharmaceuticals, such as warfarin, oral hypoglycemic agents, insulin, and phenelzine. Panax ginseng does not appear to enhance physical performance. Products with a standardized ginsenoside concentration are available.

A prostate-specific antigen (PSA)-activated vinblastine prodrug selectively kills PSA-secreting cells in vivo.

Currently, there is no therapy for men with androgen-refractory prostate cancer that substantially extends survival. This report characterizes by in vitro and in vivo techniques a new chemotherapeutic that is composed of desacetyl-vinblastine covalently linked to a peptide that contains a peptide bond that can be hydrolyzed by prostate-specific antigen (PSA). This compound (referred to as vinblastine-conjugate) is minimally toxic to cells in culture which do not express PSA. In the presence of PSA, the peptide moiety is hydrolyzed, generating several highly toxic metabolites that contain vinblastine. Animals bearing PSA-positive human prostate tumors that were treated with the vinblastine-conjugate experienced a >99% reduction in PSA serum level. In contrast, animals bearing PSA-positive human prostate tumors treated with the cytotoxic metabolites derived from the PSA hydrolysis of the vinblastine-conjugate showed a nonsignificant change in both PSA and tumor weight values. The cell killing activity of the vinblastine-conjugate is PSA dependent because animals bearing non-PSA-producing human tumor xenografts had a nonsignificant increase in tumor weight after vinblastine-conjugate treatment. Exploratory efficacy/toxicity studies in LNCaP tumor-bearing nude mice were conducted with animals treated for 5 consecutive days with various doses of either the vinblastine-conjugate or a PSA-generated toxic metabolite (desacetyl-vinblastine). The desacetyl-vinblastine treatment resulted in 10-70% mortality with a very slight effect on tumor growth. In contrast, vinblastine-conjugate treatments resulted in no mortality, good to excellent antitumor efficacy, very slight to slight peripheral neuropathy and myelopathy, and slight to severe testicular degeneration. Similar treatment of beagle dogs with the vinblastine-conjugate showed even less toxicity. These data support the use of the PSA-hydrolyzable vinblastine-conjugate as an experimental therapy for prostate cancer in man.