Concomitant Use of Steroids and Immunotherapy in a Patient With Paraneoplastic Dermatomyositis and Gastroesophageal Adenocarcinoma.

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune pathologies often associated with occult malignancies. Glucocorticoids (GCs) represent the initial therapy to control symptoms and avoid complications. Immune checkpoint inhibitors (ICIs) have shifted the paradigm of cancer treatment. Nivolumab has become the first-line therapy in combination with chemotherapy for untreated, unresectable, non-HER-2-positive advanced gastroesophageal adenocarcinoma. The use of ICIs increases the risk of immune-related adverse events (irAEs), especially in patients with autoimmune diseases, and patients receiving steroids or immunosuppressants might be associated with poorer immunotherapy efficacy. We describe the case of a 49-year-old male who was diagnosed with paraneoplastic dermatomyositis (PDM) and gastroesophageal adenocarcinoma. He was started on prednisone taper, and concomitantly, he was started on chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT), with administration of pegfilgrastim and dexamethasone during each cycle. Additionally, he was started on nivolumab. His course was complicated by worsening episodes of myopathies due to the immunotherapy, requiring adjustments to the prednisone taper. A positron emission tomography (PET) scan and repeat endoscopic ultrasonography with biopsy eight months after therapy initiation showed no major evidence of disease compared to prior. In our case, we exemplified the importance of multidisciplinary management for dosing and tapering of GCs and timing of ICI initiation, and we described the successful response to nivolumab in a patient with autoimmune disease concurrently receiving GCs.

Improvement from ixekizumab treatment in patients with psoriatic arthritis who have had an inadequate response to one or two TNF inhibitors.

OBJECTIVE: To evaluate the efficacy of ixekizumab (IXE), a monoclonal antibody selectively targeting interleukin-17A, in patients with inadequate response to one or two TNF inhibitors (TNFi). METHODS: A phase 3 study (SPIRIT-P2; NCT02349295) randomized patients with PsA with inadequate response or intolerance to one or two TNFi to receive 80-mg IXE every 2 weeks (n = 123) or every 4 weeks (n = 122) after a 160-mg starting dose or placebo (PBO; n = 118) through week 24. This post hoc analysis used data from inadequate responders to one or two TNFi, measuring the percentage achieving: ≥50% improvement in ACR response criteria (ACR50) and 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI 100), ACR50, improvement in HAQ-Disability Index (HAQ-DI) ≥0.35, minimal disease activity (MDA), European League Against Rheumatism (EULAR) Good Response Criteria [improvement in Disease Activity Score 28 CRP (DAS28-CRP) >1.2], and Disease Activity in PsA (DAPSA) ≤14. RESULTS: There were no significant differences in baseline characteristics between inadequate responders to one and two TNFi. At week 24, significantly more patients irrespective of previous TNFi experience receiving IXE than PBO achieved ACR50, HAQ-DI ≥0.35 improvement, MDA, EULAR good response, and DAPSA ≤14, and significantly more patients with inadequate response to one TNFi receiving IXE than PBO achieved ACR50 and PASI 100. Improvement persisted in all measures through week 52. CONCLUSION: IXE improved the signs and symptoms of PsA in a population of difficult-to-treat patients with inadequate response to one or two TNFi.

Osteochondral defects of the talus with a focus on platelet-rich plasma as a potential treatment option: a review.

OBJECTIVE: To provide a review of osteochondral lesions of the talus, to discuss the evidence of the risks and benefits of platelet-rich plasma (PRP) as a viable treatment option, and to measure the efficacy of PRP using MRI evidence of cartilage regeneration, as well as scales that measure improvement in 'pain' and 'functionality'. ELIGIBILITY CRITERIA: Studies that use PRP in either conservative or intraoperative settings to treat osteochondral defects of the talus. RESULTS: There are seven studies that compare hyaluronic acid or standard surgical options against PRP in treating osteochondral lesions of the talus. Five studies use PRP as supplemental treatment in intraoperative settings, while two studies use PRP conservatively as intra-articular injections. There were minimal adverse effects. Pain and functionality scores consistently improved in those who underwent PRP treatments over the course of 4 years. MRI showed significant but inconsistent results in chondral regeneration. CONCLUSION: PRP may show clinical benefit in those with osteochondral lesions of the talus in terms of pain and functionality, although chondral regeneration via MRI is inconsistent. Limitations include the small sample sizes in these seven studies, as well as no standardised formula for PRP preparation. CLINICAL RELEVANCE: To serve as an overview of the literature regarding PRP treatment for osteochondral lesions of the talus and how this modality may improve patient outcomes in pain, functionality and chondral regeneration. A case is reported to complement the subject review.

A rare case of prototheca algaemia in a patient with systemic lupus erythematosus and recent belimumab infusion.

Novel agents for the treatment of immune-mediated diseases such as systemic lupus erythematosus (SLE) have been increasingly used as an alternative to or in combination with conventional therapies. Belimumab, a human monoclonal antibody that inhibits B-cell activating factor (BAFF), has demonstrated efficacy in moderate-to-severe SLE with similar adverse effects when compared to other biologic agents and conventional SLE therapies. Here, we describe a woman with SLE and diabetes mellitus (DM) on immunosuppressive therapy for five years who was admitted to the hospital for pneumonia but had a complicated hospital course with multiple infections and, most notably, a nosocomial algaemia due to Prototheca wickerhamii, which was treated successfully with amphotericin B. She had recently received three belimumab infusions as an outpatient prior to admission to the hospital. To the best of our knowledge no cases of human protothecosis in patients receiving belimumab have been described in the English literature; however, unusual infections have to be considered in all patients undergoing immunosuppressive therapies who persist with fever despite conventional antimicrobials.

Remission in rheumatoid arthritis: wishful thinking or clinical reality?

OBJECTIVES: To review the concept of remission in rheumatoid arthritis (RA), as defined by the Food and Drug Administration (FDA), the American College of Rheumatology (ACR), and the European League Against Rheumatism (EULAR). To delineate differences between significant clinical improvements, very low disease activity, and the achievement of true remission. To evaluate the prevalence of these outcomes with biologic therapy and traditional disease-modifying antirheumatic drugs (DMARD) regimens. METHODS: The MEDLINE database was searched for the key words "remission" and "rheumatoid arthritis." Efficacy data of RA clinical trials from 1985 to 2004 are based on a literature review of medical journals and abstracts from rheumatology meetings. We review 3 well-defined sets of criteria established by the ACR, EULAR, and the FDA for measuring remission. RESULTS: Defining remissions in clinical trials and clinical practice requires appropriate standardized and objective outcome measures, such as the ACR and EULAR remission criteria. Traditional DMARDs often provide symptom relief, improvements in physical function, and the slowing of radiographic progression in patients with RA, but rarely lead to the complete cessation of RA activity. Remission, as defined by the ACR criteria, has been observed in 7 to 22% of patients treated with traditional DMARD monotherapy (ie, gold, penicillamine, methotrexate [MTX], cyclosporine A, or sulfasalazine), but these remissions have often been short-lived. Treatments with DMARD combinations, biologic monotherapy, and biologic combination therapy with MTX offer greater hope and may facilitate the higher rates of remission. Clinical trial results have shown that newer DMARDs such as leflunomide or the combination of multiple DMARDs can generally elicit greater EULAR remission rates (ranging from 13 to 42%) than monotherapies. Biologic combinations with MTX have also been shown to induce significant remission (as defined by the EULAR criteria) in RA patients, with a 31% rate observed with infliximab plus MTX at 54 weeks, a 50% rate observed for adalimumab plus MTX after 2 years of therapy, and a 41% rate observed for etanercept plus MTX after 2 years of therapy. CONCLUSIONS: In the era of biologics and combination therapy, identifying remission or at least very low disease activity as the ultimate goal in RA therapy should become the new standard for the outcome of all RA trials. The criteria established by the FDA, the ACR, and the EULAR represent an important step toward achieving this goal.

Shedding of endothelial protein C receptor contributes to vasculopathy and renal injury in lupus: in vivo and in vitro evidence.

BACKGROUND: Candidate biomarkers for vasculopathy in systemic lupus erythematosus (SLE) include circulating endothelial cells and the recently identified endothelial protein C receptor (EPCR) which, when shed, promotes a thrombotic diathesis. This study sought correlation between plasma levels of soluble EPCR and disease manifestation/severity, with a focus on lupus nephritis. METHODS: In 81 SLE patients (evaluated cross-sectionally and longitudinally) and 59 healthy controls, levels of soluble EPCR and soluble E-selectin were assessed by sandwich enzyme-linked immunosorbent assay (ELISA), circulating endothelial cells isolated by immunomagnetic separation, and EPCR gene polymorphisms determined. Mechanisms of vascular injury were addressed in vitro in human aortic endothelial cells (HAEC) cultured in the presence and absence of interferon-gamma (IFN-gamma). RESULTS: The mean level of soluble EPCR was significantly higher in SLE patients (263 +/- 13 ng/mL) than controls (174 +/- 11 ng/mL) (P < 0.0001). Patients with active or past renal involvement had significantly higher mean soluble EPCR levels (306 +/- 21 ng/mL) (N= 40) than patients without nephritis (228 +/- 14 ng/mL) (N= 41) (P= 0.0033). Mean soluble EPCR correlated positively with serum creatinine (R= 0.3429, P < 0.0001). The prevalence of the enhanced-shedding EPCR polymorphism A6936G was higher in SLE (41%) (N= 27) than controls (7%) (N= 29) (P= 0.0039). Patient and control plasma were also interrogated for soluble E-selectin, a comparator plasma marker. The results suggest that soluble E-selectin and soluble EPCR are not equivalent end points of vasculopathy and endothelial perturbation in SLE. Although in SLE patients the absence or diminished expression of membrane EPCR on circulating endothelial cells varied, the rare circulating endothelial cells detected in controls invariably expressed membrane-bound EPCR. IFN-gamma-treated HAEC expressed less membrane-bound EPCR [133 relative fluorescence units (rfu)] than untreated HAEC (275 rfu); more soluble EPCR was detected in IFN-gamma-treated (1.1 ng/10(6) cells) than untreated HAEC (0.65 ng/10(6) cells) (P= 0.027). CONCLUSION: The results obtained from this cross-sectional/longitudinal study support the hypothesis that the vascular dysfunction characteristic of SLE may be related to a dramatically altered distribution of EPCR, both soluble and membrane-bound forms.