Síndrome de Hedinger secundario a Tumor neuroendocrino bronquial. Presentación de un caso

El síndrome carcinoide es un síndrome paraneoplásico que se presenta en tumores neuroendocrinos. Aunque es una entidad infrecuente suele ser la primera manifestación de la enfermedad. La baja incidencia junto a la presentación inespecífica genera retrasos diagnósticos importantes. Se presenta el caso de una paciente con síntomas digestivos y tuforadas que posteriormente agrega insuficiencia cardíaca, logrando mediante un ecocardiograma típico y marcadores analíticos el diagnóstico de síndrome carcinoide. Posteriormente se evidencia que su origen en un tumor neuroendocrino bronquial. Conocer las características de este síndrome es fundamental para mantener una alta sospecha clínica en pacientes con síntomas sugestivos logrando un diagnóstico precoz y adecuado.

Carcinoid syndrome is a paraneoplastic syndrome that occurs in neuroendocrine tumors. Although It is an uncommon entity, it is usually the first manifestation of the disease. The low incidence besides the non-specific presentation generates important diagnostic delays. We present the case of a patient presenting digestive symptoms and flushing that subsequently adds heart failure, achieving though a typical echocardiogram and analytical markers the diagnosis of carcinoid syndrome. Later it is discovered its origin in a bronchial neuroendocrine tumor. Knowing the characteristics of this syndrome is essential to maintain a high clinical suspicion in patients with suggestive symptoms, in order to achieve an early and adequate diagnosis.

El síndrome carcinoide é um síndrome paraneoplásico que ocorre em tumores neuroendócrinos. Embora seja uma entidade rara, geralmente é a primeira manifestação da doença. A baixa incidência, juntamente com a apresentação inespecífica, resulta em atrasos importantes no diagnóstico. Apresentamos o caso de uma paciente com sintomas digestivos e ruborização cutânea, que posteriormente desenvolve insuficiência cardíaca. O diagnóstico de síndrome carcinoide foi estabelecido por meio de um ecocardiograma característico e marcadores analíticos. Posteriormente, foi evidenciada a origem em um tumor neuroendócrino brônquico. Conhecer as características deste síndrome é fundamental para manter uma alta suspeita clínica em pacientes com sintomas sugestivos, permitindo um diagnóstico precoce e adequado.

Tumor fibroso calcificante intestinal: reporte de caso / Intestinal calcifying fibrous tumor: case report

El tumor fibroso calcificante (TFC) es una inusual lesión benigna de origen mesenquimal que puede presentar características similares a otros tumores más comunes. El caso involucra a una mujer de 36 años con un tumor en el yeyuno proximal, inicialmente sospechoso de ser un tumor del estroma gastrointestinal (GIST). Se realiza una resección quirúrgica, revelando un nódulo bien delimitado en el borde antimesentérico con características microscópicas típicas de TFC. Las células tumorales presentaban positividad para CD34 y negatividad para demás marcadores, diferenciándolo de otras neoplasias. El TFC puede confundirse con tumores más comunes debido a su apariencia, pero un diagnóstico preciso respaldado por inmunohistoquímica es esencial. La extirpación quirúrgica completa suele ser curativa. (AU)

Calcifying fibrous tumor (CFT) is a rare benign lesion of mesenchymal origin that may present similar characteristics to other more common tumors. We present the case of a 36-year-old woman with a tumor in the proximal jejunum, initially suspected to be a gastrointestinal stromal tumor (GIST). Surgical resection was performed, revealing a well-demarcated nodule at the anti-mesenteric border with microscopic features typical of a calcifying fibrous tumor. The tumor cells were positive for CD34 and negative for other markers, differentiating it from other neoplasms. Calcifying fibrous tumors can be confused with more common tumors because of its appearance, but an accurate diagnosis supported by immunohistochemistry is essential. Complete surgical excision is usually curative. (AU)

Tumor espermatocítico variante anaplásica sincrónico bilateral: reporte de una neoplasia infrecuente / Bilateral synchronous anaplastic variant spermatocytic tumor: Report of a rare neoplasm

El tumor espermatocítico es una neoplasia testicular de células germinales, muy infrecuente, que representa menos del 1% de los cánceres testiculares. Afecta generalmente a hombres mayores con una edad media de 53,6 años (rango 19-92 años). El tumor espermatocítico se clasifica dentro del grupo de tumores germinales no relacionados con la neoplasia de células germinales in situ. Muestra características clinicopatológicas diferentes del seminoma clásico y no se considera una variante de este último. Debido a una superposición morfológica con el seminoma clásico, en el pasado se denominó «seminoma espermatocítico». La variante anaplásica del tumor espermatocítico es excepcional, se han descrito pocos casos en la literatura, presenta un inicio más temprano en comparación con el tumor espermatocítico y un buen comportamiento a pesar de mostrar patrones histológicos similares al seminoma clásico. Presentamos el segundo caso de tumor espermatocítico anaplásico sincrónico bilateral, en un paciente joven tratado con orquiectomía y quimioterapia. (AU)

Spermatocytic tumor is a very rare germ cell testicular neoplasm that accounts for less than 1% of testicular cancers. It generally affects older men with a mean age of 53.6 years (range 19-92 years). Spermatocytic tumor is classified within the group of germ cell tumors not related to germ cell neoplasia in situ. It presents clinicopathological characteristics different from classic seminoma and is not considered a variant of the latter. Due to a morphologic overlap with classical seminoma, it was called “sperm cell seminoma” in the past. The anaplastic variant of spermatocytic tumor is exceptional, few cases have been described in the literature, it presents an earlier onset compared to spermatocytic tumor and a benign behavior despite showing histological patterns similar to classic seminoma. We present the second case of bilateral synchronous anaplastic spermatocytic tumor, in a young patient treated with orchiectomy and chemotherapy. (AU)

Tumor analysis of MMR genes in Lynch-like syndrome: Challenges associated with results interpretation.

BACKGROUND: Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. Moreover, translating tumor testing results into patient management remains controversial. Our aim is to assess the challenges associated with the implementation of tumoral MMR gene testing in routine workflows. METHODS: Here, we present the clinical characterization of 229 LLS patients. MMR gene testing was performed in 39 available tumors, and results were analyzed using two variant allele frequency (VAF) thresholds (≥5% and ≥10%). RESULTS AND DISCUSSION: More biallelic somatic events were identified at VAF ≥ 5% than ≥10% (35.9% vs. 25.6%), although the rate of nonconcordant results regarding immunohistochemical pattern increased (30.8% vs. 20.5%). Interpretation difficulties question the current utility of the identification of MMR somatic hits in the diagnostic algorithm of suspected LS cases.

A Primary Pulmonary Meningioma That Grew Over 10 Years: A Surgical Case Report.

Primary pulmonary meningiomas (PPMs) are rare meningothelial proliferation that lacks characteristic imaging findings, making their distinction from other peripheral lung tumors challenging. Therefore, surgical resection is often performed for the diagnosis and treatment of PPM. Herein, we describe a surgical case of PPM that grew over 10 years. A 63-year-old woman was referred to our department due to right middle lobe lung tumor enlargement. No significant symptoms were observed. Chest computed tomography revealed a tumor in the middle lobe of the right lung. F-18 fluorodeoxyglucose positron emission tomography showed accumulation in the nodule; thus, lung cancer could not be ruled out. Therefore, the preoperative differential diagnosis was cStageIB lung cancer. A right middle lobectomy was performed, and a histopathology examination revealed meningioma. There were no primary lesions in the head and whole spine magnetic resonance imaging, thus, a final diagnosis of PPM was made. Cautious observation is required postoperatively due to the possibility of recurrence.

Incidentally Found Rectal Carcinoid Tumor in a 46-Year-Old Female: The Potential for Complications and the Importance of Screening Guidelines.

Carcinoid tumors are rare neuroendocrine tumors that can be found in the gastrointestinal tract as well as other areas throughout the body. The neurosecretory nature of these tumors can have implications for other chronic diseases that patients may have, such as diabetes. Certain treatments that may be implemented for patients who have carcinoid tumors, such as somatostatin analogs and Everolimus, can also alter blood glucose control. This highlights the importance of diagnosing and treating carcinoid tumors as early as possible to avoid complications associated with metastasis and more intense treatment. With more advanced diseases, clinicians should consider the possible effects of carcinoid tumors and their treatments on other chronic conditions as they manage the patient. For gastrointestinal carcinoid tumors, colonoscopy screening guidelines are incredibly important to counsel patients on, as resection can yield a complete cure for carcinoid tumors when they are found at an early stage. Here, we describe the case of an incidentally diagnosed rectal carcinoid tumor in a 46-year-old female patient with a history of type 2 diabetes mellitus and hypertension.

Tumor Thrombus of Hepatocellular Carcinoma: A Direct Extension From the Liver to the Right Atrium.

Hepatocellular carcinoma (HCC) is a very aggressive type of cancer and can either invade or spread distantly through the portal vein to the inferior vena cava (IVC) and the right atrium (RA). The presentation varies based on the stage of the cancer at the time of diagnosis. Liver transplantation or surgical resection is the ideal management of small lesions without metastases, while systemic therapy can help in extensive cases to decrease the tumor burden to allow surgical resection of the tumor. We present a rare case of HCC with a tumor thrombus (TT) extending to the RA. Unfortunately, the patient did not survive the cancer. We hope that this case report can contribute to saving the lives of future patients with HCC.

From Black Stools to Gastrointestinal Stromal Tumor (GIST): A Case Report and Literature Review on This Unsuspected Danger.

This case report presents the clinical details of a 42-year-old female without previous medical issues who presented with upper gastrointestinal bleeding (UGIB) characterized by melanotic stools. Initial examination revealed mild anemia and subsequent endoscopy identified a 4 cm submucosal gastric mass displaying recent bleeding indicators. Subsequent surgical pathology confirmed a high-grade gastrointestinal stromal tumor (GIST) of grade 2 with a heightened risk of recurrence. The significance of this case lies in underscoring the necessity of considering GIST in the differential diagnosis of UGIB, particularly among middle-aged individuals with no identifiable risk factors such as recent or chronic non-steroidal anti-inflammatory drug (NSAID) use, peptic ulcer disease, or alarm symptoms. Early detection and prompt surgical intervention assume paramount importance in enhancing patient outcomes. While complete resection stands as the cornerstone of treatment, adjuvant imatinib therapy is recommended for high-risk patients to mitigate the risk of recurrence.

Unveiling Enigma: Navigating the Diagnostic Labyrinth of an Atypical Medial Clavicular Enchondroma.

Benign cartilaginous lesions called enchondromas usually appear in the long bones of the limbs. This case report, however, draws attention to an uncommon and unusual appearance of enchondroma near the medial end of clavicle. Because of the unusual location, the diagnostic process was very complex, which presented a challengefor the physicians. We provide the clinical, radiological and histological results that finally allowed for an accurate diagnosis. This example highlights the need of taking into account atypical location for benign lesions and highlights the necessity of a thorough diagnostic approach in unexpected clinical settings. Since the occurrence of clavicular enchondromas is a rare entity and can at times mislead the clinician, healthcare providers must be vigilant enough to guarantee a prompt and accurate diagnosis for timely intervention.

Urothelial Carcinoma With Bone Metastasis Mimicking Sciatica: A Common Neoplasm With an Uncommon Presentation.

Bone metastasis in urothelial cancer is underreported and not well-researched. A case of urothelial carcinoma (UC) with bone metastasis presenting as musculoskeletal pain is reported. The patient presented with persistent lower back pain associated with right lower extremity pain, numbness, and tingling. Initially, a diagnosis of sciatica was suspected, but the patient did not respond to treatment. An MRI spine was done, which revealed a bright signal mass in the vertebral body suspicious for a metastatic lesion, left hydroureteronephrosis, and a nonspecific cystic focus in the right iliacus muscle. Subsequent imaging revealed an irregular soft tissue mass at the left posterolateral bladder base, resulting in apparent obstruction of the left ureter, highly suggestive of neoplasm, along with numerous lytic bone lesions in the pelvic girdle with associated soft tissue masses, consistent with metastatic disease. The patient underwent an interventional radiology biopsy of the right iliac soft tissue mass to evaluate the lytic bony lesions, which revealed metastatic carcinoma, consistent with UC. A prompt referral was made for urology and oncology consultations. The patient underwent left percutaneous nephrostomy placement for obstruction, but he was not a candidate for any systemic therapy because of his poor performance status, and hospice was recommended as his metastatic disease was not curable and the goal of any kind of treatment was palliative. The optimal treatment for UC with bone metastasis remains divergent, and the management options should be determined as part of a shared decision-making process. This case highlights the importance of having a high suspicion of neoplastic pathology in patients presenting with musculoskeletal pain, like back pain, and not responding to treatment. This should alert the physicians to the potential for serious disease processes.

Clinical Trial Protocol for "Replace Cysto": Replacing Invasive Cystoscopy with Urine Testing for Non-muscle-invasive Bladder Cancer Surveillance-A Multicenter, Randomized, Phase 2 Healthcare Delivery Trial Comparing Quality of Life During Cancer Surveillance with Xpert Bladder Cancer Monitor or Bladder EpiCheck Urine Testing Versus Frequent Cystoscopy.

"Replace Cysto" is a multisite randomized phase 2 trial including 240 participants with low-grade intermediate-risk non-muscle-invasive bladder cancer, in which participants will be randomized 1:1:1 to one of two urine marker-based approaches alternating a urine marker test (Xpert Bladder Cancer Monitor or Bladder EpiCheck) with cystoscopy or to frequent scheduled cystoscopy. The primary objective is to determine whether urinary quality of life after surveillance is significantly improved in the urine marker arms. The primary outcome will be the patient-reported urinary quality of life domain score of the validated QLQ-NMIBC24 instrument, measured 1-3 d after surveillance. Exploratory outcomes include discomfort after surveillance, the number of invasive procedures that participants undergo per 1000 person years, complications from these procedures per 1000 person years, nonurinary quality of life, acceptability of surveillance, and bladder cancer recurrence and progression. Comparators include surveillance using (1) the Xpert Bladder Cancer Monitor test, (2) the Bladder EpiCheck urinary marker, or (3) frequent cystoscopy alone. After a negative cystoscopy ≤4 mo following bladder tumor resection, all the participants will undergo surveillance at 6, 12, 18, and 24 mo (with time zero defined as the date of the most recent bladder tumor resection). In the urine marker arms, surveillance at 6 and 18 mo will be performed with the marker. Regardless of the arm, participants will undergo cystoscopy at 12 and 24 mo. End of study for each participant will be their 24-mo cystoscopy. Overall trial duration is estimated at 5 yr from when the study opens to enrollment until completion of data analyses. The trial is registered at clinicaltrials.gov (NCT05796375).

Thymic NK-Cells and Their Potential in Cancer Immunotherapy.

Natural killer (NK)-cells are innate immune cells with potent anti-tumor capacity, capable of recognizing target cells without prior exposure. For this reason, NK-cells are recognized as a useful source of cell therapy. Although most NK-cells are derived from the bone marrow (BM), a separate developmental pathway in the thymus also exists, producing so-called thymic NK-cells. Unlike conventional NK-cells, thymic NK (tNK)-cells have a combined capacity for cytokine production and a natural ability to kill tumor cells in the presence of NK-cell receptor stimulatory ligands. Furthermore, tNK-cells are reported to express CD3 subunits intracellularly, without the presence of a rearranged T-cell receptor (TCR). This unique feature may enable harnessing of these cells with a TCR to combine NK- and T-cell effector properties in one cell type. The development, phenotype, and function of tNK-cells, and potential as a cell therapy is, however, poorly explored. In this review, we provide an overview of current literature on both murine and human tNK-cells in comparison to conventional BM-derived NK-cells, and discuss the potential applications of this cellular subset in the context of cancer immunotherapy.

Tibial Adamantinoma: A Case Report from a Resource-Limited-Setting.

Introduction: Adamantinoma is an infrequent, low-grade malignant bone tumor, predominantly affecting the tibia and often presents diagnostic challenges due to its nonspecific radiographic characteristics. Case Presentation: A 55-year-old military personnel, with no history of trauma, who presented with a one-year history of right leg swelling and pain. Radiological examination showed right anterior tibial, mid diaphyseal lytic expansile lesion with internal trabeculations and excisional biopsy led to the diagnosis of adamantinoma. Below knee amputation was done as a definitive management. Conclusion: Despite diagnostic challenges adamantinoma presents, the patient was referred to oncology and underwent amputation, underscoring the importance of considering adamantinoma in differential diagnosis for persistent bone lesions.

Extensive Osteochondroma of the Talus Presenting As Syndesmotic Joint Extension and Posterior Inferior Tibiofibular Ligament Rupture: A Reportof a Rare Case and a Review of the Literature.

This case report describes a rare occurrence of talar osteochondroma extending into syndesmosis, causing disruption of the interosseous membrane and the posterior inferior tibiofibular ligament (PITFL). This type of presentation for a talar osteochondroma is the first of its kind reported in the literature based on current knowledge. A detailed preoperative radiological assessment was crucial in planning the surgical approach and preparing for syndesmotic stabilization during the excision. The patient underwent successful and complete excision of the osteochondroma, and the syndesmosis was stabilized using a cortical screw along with anatomical repair of the PITFL. Apart from delayed wound healing, the patient exhibited good functional outcomes in terms of gait and ankle range of motion at the six-month follow-up. This case serves as a valuable reference for similar presentations in the future, emphasizing the importance of thorough preoperative assessment and appropriate treatment planning.

Prosopagnosia Due to Metastatic Brain Tumor: A Case-Based Review.

Prosopagnosia, also referred to as "face blindness," is a type of visual agnosia characterized by a decreased capacity to recognize familiar faces with a preserved ability to identify individuals based on non-facial visual traits or voice. Prosopagnosia can be categorized as developmental (DP) or acquired (AP) owing to a variety of underlying conditions, including trauma, neurodegenerative diseases, stroke, neuroinfections, and, less frequently, malignancies. Facial recognition is a complex process in which different neuronal networks are involved. The infrequent but notable higher visual-processing abnormalities can be caused by lesions of the inferior longitudinal fasciculus (ILF) in the non-dominant temporal lobe. We report a rare case of AP in a 69-year-old patient who is right-hand dominant with rectal carcinoma cerebral metastases. The patient complained of dizziness, vertigo, falls, and trouble recognizing her family members' faces. The CT scan of the head with contrast revealed two metastatic brain lesions with vasogenic edema, as one of them was in the right cerebellar hemisphere, causing dislocation and compression of the ILF. Corticosteroids and osmotherapy were utilized as a conservative treatment approach, which resulted in the prosopagnosia being completely withdrawn. In conclusion, patients with primary brain tumors or metastatic disease rarely present with an isolated cognitive deficit such as prosopagnosia. Based on the anatomical features and the personalized approach, a conservative or surgical approach may be useful to improve higher cortical functioning.

Postmenopausal Hyperandrogenism Associated With Synchronous Ovarian Brenner Tumor, Bilateral Leydig Cell Tumor, and Adrenal Mass.

Hyperandrogenism in postmenopausal females may arise from either ovarian or adrenal sources and can pose a challenging diagnostic dilemma. We present the case of a 66-year-old female with postmenopausal hyperandrogenism with virilization, adrenal incidentaloma, and concurrent finding of two extremely rare ovarian tumors, including bilateral Leydig cell tumor and Brenner tumor. Laboratory tests showed elevated testosterone and androstenedione and normal dehydroepiandrosterone sulfate (DHEAS). Response to 1 mg overnight dexamethasone suppression test demonstrated persistently elevated testosterone and incomplete suppression of androstenedione. Computed tomography (CT) scan showed a left adrenal nodule and an unremarkable appearance of the ovaries. The pelvic ultrasound did not show an ovarian tumor on the right ovary, and the left ovary was not seen. Adrenal and ovarian vein sampling suggested the ovaries as the source of the testosterone. Given the ovarian vein sampling results, a multidisciplinary discussion between endocrinology and gynecologic oncology concluded that bilateral salpingo-oophorectomy (BSO) was the next best step for diagnosis and management. Laparoscopic BSO was performed. Histopathology showed bilateral Leydig cell tumors and a left ovarian Brenner tumor. At one-year postoperative follow-up, alopecia improved, and testosterone level normalized. This case highlights the importance of diagnostic pathways and interdisciplinary collaboration in managing rare clinical scenarios of hyperandrogenism in postmenopausal females. As in our case, surgeons may be hesitant to remove normal-appearing ovaries. While the three presented tumor types in this case arise from distinct tissues and exhibit different histological characteristics, the presence of such a unique triad prompts consideration of potential unifying pathogenic mechanisms.

Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Background: Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. Objective: This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Methods: Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. Results: 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). Conclusion: When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

Case report: Isolated eyelid metastasis of ccRCC 5 years after receiving radical nephrectomy.

Introduction: The most common sites of clear cell renal cell carcinoma(ccRCC) metastasis are the lung, bones, liver and brain; eyelid metastasis is a rare occurrence. Case presentation: We report a case of ccRCC metastasis to the left eyelid after radical nephrectomy, and remission after sunitinib treatment. Conclusions: Although the probability of eyelid metastasis rate is very low, tumor metastasis to the eyelid skin is possible after radical nephrectomy. Therefore, any rash like changes on the skin during the review procedure cannot be ignored by the physician.

Mediastinal malignant rhabdoid tumor in an infant: A rare case report.

Mediastinal malignant rhabdoid tumor (MRT) is an exceedingly rare and aggressive neoplasm, particularly uncommon in infants. We present the case of a previously healthy 7-month-old male infant with mediastinal MRT. The patient initially presented with left eyelid ptosis and was otherwise asymptomatic. Initial investigations, including brain MRI, yielded unremarkable results, and the infant was discharged with vitamin B supplements. However, he was readmitted a week later with prolonged fever, poor feeding, diarrhea, and respiratory distress. Despite an initial diagnosis of bronchiolitis/viral respiratory tract infection, the patient's condition rapidly deteriorated. Subsequent evaluation revealed mediastinal MRT as the underlying cause. This case underscores the diagnostic challenges associated with mediastinal MRT in infants and highlights the importance of considering rare neoplastic etiologies in atypical clinical presentations.

Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.