Clinical Characteristics of Korean Rheumatoid Arthritis Patients with Indications for TNF-alpha Blocker

OBJECTIVE: The aim of this study was to examine clinical characteristics of Korean rheumatoid arthritis (RA) patients with clinically indications for TNF-alpha blocker, and to compare their clinical parameters with the Korean National Health Insurance reimbursement criteria. METHODS: Data were obtained from a registry of RA patients who visited rheumatology clinics of Hallym University affiliated hospitals. Among patients who were previously prescribed DMARDs for more than three months, rheumatologists selected patients clinically indicated for TNF-alpha blocker. The clinical characteristics at the time TNF-alpha blocker use was deemed indicated were examined. Radiographic damage was quantified by Modified Sharp van der Heijde score in hand and foot simple AP radiograph. RESULTS: From August 2010 to January 2013, five rheumatologists in four hospitals selected 109 patients clinically indicated for TNF-alpha blocker. When TNF-alpha blocker was considered, mean DAS28 was 5.2 (range 2.1~8.05), mean swollen joint count was 6 (range 0~22), mean tender joint count was 10.6 (range 0~28), mean ESR was 43.2 mm/hr (range 1~140) and mean CRP was 2.5 mg/dL (range 0.1~18.3). The mean total modified Sharp van der Heijde score was 32.72 (range 0~240). Eighty one percent of subjects did not have enough active joints to satisfy the Korean National Health Insurance reimbursement standard. CONCLUSION: Our results show that patients with clinically indications for TNF-alpha blocker had a broad range of disease activity and clinical parameters, and the majority did not meet the Korean National Health Insurance reimbursement criteria.

Comparison Korean National Health Insurance Reimbursement and Other Guidelines for TNF-alpha Blocker in Rheumatoid Arthritis

OBJECTIVE: The aim of this study was to examine how many Korean rheumatoid arthritis (RA) patients fulfilling the 2008 American College of Rheumatology (ACR) recommendation, 2007 British Society for Rheumatology (BSR) guideline and 2010 Japan College of Rheumatology (JCR) guideline for TNF-alpha blocker, meet the Korean National Health Insurance reimbursement criteria and to evaluate the reasons for failing the Korean National Health Insurance reimbursement criteria. METHODS: Data were obtained from a registry of RA patients who visited rheumatology clinics of Hallym university affiliated hospitals. Patients who were previously prescribed with methotrexate or leflunomide for more than 3 months and had at least one DAS28 examination were included in the present study. RESULTS: Of 642 patients included, 118 episodes meeting ACR guideline for using TNF-alpha blocker were identified in 88 patients (13.7%). In addition, 19 episodes meeting BSR guideline in 17 patients (2.6%) and 21 episodes meeting JCR guideline in 21 patients (6.2%) were identified. Four episodes (4.8%) meeting ACR recommendation, 0 episodes meeting BSR criteria and 5 episodes (12%) meeting JCR criteria, respectively, were eligible for TNF-alpha blocker according to the Korean National Health Insurance reimbursement guideline. The most common reason for failing the Korean National Health Insurance reimbursement criteria was the number of active joint counts (92.6%). CONCLUSION: Our results show that the majority of RA patients satisfying the ACR guideline, BSR and JCR guideline for use of the TNF-alpha blocker did not meet the Korean National Health Insurance reimbursement criteria. Patients most often failed due to active joint count criteria.

A Case of Refractory SAPHO Syndrome Treated with Etanercept

SAPHO syndrome, which has different skin changes and osteoarticular inflammation, is an acronym that stands for synovitis, acne, pustulosis, hyperostosis, and osteitis. Treatment of SAPHO syndrome includes non-steroidal anti-inflammatory drugs (NSAIDs), anti-rheumatic drugs, such as colchicines, corticosteroids and bisphosphonates, and disease-modifying agents. However, the treatment of SAPHO syndrome is controversial because it is a new clinical entity with unclear etiopathogenesis and inadequate clinical studies. We report a case with refractory SAPHO syndrome, which was successfully treated with a tumor necrosis factor (TNF)-alpha blocker.

Repeated Paradoxical Aggravation of Preexisting Psoriasis during Infliximab Treatment for Crohn's Disease

As more rheumatologists and dermatologists have begun to use biological agents such as TNF-alpha blocker, they have confronted an unexpected complication: psoriasis was paradoxically aggravated or induced by the TNF-alpha blocker. Although it is not a common complication of TNF-alpha blocker, this aggravation may be more common than previously thought. To our knowledge, most reports about TNF-alpha blocker-induced psoriasis have been limited to western countries while only a few cases have been reported in Korea and Japan. In addition, new onset of pustular psoriasis by TNF-alpha blocker has been reported more commonly than worsening of preexisting psoriasis. Now we report a patient whose preexisting psoriasis vulgaris was aggravated repeatedly after using the TNF-alpha blocker, infliximab, to control Crohn's disease, which is a rare rheumatologic disease in Korea.

A Case of Cryptococcal Pneumonia in a Rheumatoid Arthritis Patient after Tumor Necrosis Factor-alpha Antagonist Therapy / 대한류마티스학회지

Tumor necrosis factor-alpha (TNF-alpha) plays a important role in the pathogenesis of rheumatoid arthritis and Crohn's disease, TNF-alpha antagonist has been widely used for these disease, but it also plays a major role in cell mediated immunity. Cryptococcus neoformans, an encapsulated, ubiquitous environmental yeast, is pathogenic for humans, primarily those with compromised immune function. Cryptococcus neoformans is believed to be a facultative intracellular pathogen. We report a case of pulmonary cryptococcosis after chimeric anti-TNF monoclonal antibody therapy. No case has been reported in Korea for the best of our knowledge. A 66-year old woman was admitted because of severe cough. She was diagnosed to have rheumatoid arthritis 4 years ago and taken prednisolone and methotrexate. She was started on infliximab and received ten doses, the last dose being administered 6 weeks prior to above symptom. Chest PA and computed tomography of chest revealed multifocal consolidative lesions in both lungs. Pulmonary cryptococcosis confirmed by thoracoscopic lung biopsy tissue stained with Grocott-Gomori methenamine-silver (GMS). Initially the lung lesion responded to amphotericin B but leukopenia developed after 12 days of treatment. It was changed to fluconazole, then leukopenia and the pneumonia also improved. Physicians should remind pulmonary cryptococcosis in patients receiving TNF-alpha antagonist therapy.

A Case of Steroid Refractory Acute GVHD Treated with IL-2 & TNF-alpha Blocker in a Myelodysplastic Syndrome Patient who Underwent Unrelated Allogeneic Stem Cell Transplantation

Hematopoietic stem cell transplantation has evolved as a central treatment modality for the management of various hematologic malignancies. Despite adequate posttransplantation immunosuppressive therapy, acute GVHD remains a major cause of morbidity and mortality, even for the patients who have received HLA identical sibling grafts. Once established, acute GVHD is difficult to treat, and the best primary treatments such as corticosteroid have shown responses of approximately 50%. Once GVHD becomes steroid-refractory, the chances of survival are slim at best, and the possibility of long-term complications from chronic GVHD is almost always the rule. Many agents are currently being evaluated to treat this malady, including ATG, monoclonal antibodies, pentostatin, denileukin diftitox, etc. We reported here on a case of steroid refractory acute GVHD that was treated with IL-2 and TNF-alpha blocker in myelodysplastic syndrome patient who underwent unrelated allogeneic stem cell transplantation.

Refractory Cases of Adult Onset Still's Disease Successfully Treated with TNF-alpha Blocker / 대한류마티스학회지

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology characterized by spiking fever, evanescent salmon-colored rash, polyarthritis and leukocytosis. The diagnosis of AOSD remains a challenge to clinicians and requires a high index of suspicion because of its rarity and nonspecific symptoms. Although the etiology and pathogenesis of AOSD is not elucidated clearly, the pathogenetic role of inflammatory cytokines, such as interleukin (IL)-6, IL-8, IL-18 and tumor necrosis factor (TNF)-alpha were suggested and the correlations of their levels with disease activity were also reported. These results raise a possibility that the blocking of these cytokines may provide a therapeutic benefit in controlling disease activity and relieving the symptoms of AOSD. Recently, we experienced two cases of AOSD, who were refractory to the treatment with high dose glucocorticoid and immunosuppressive agents. Both were treated with TNF- blockers and experienced remissions thereafter. These experiences might support the use of biologic agents in refractory AOSD.

Biologic Therapy in Rheumatoid Arthritis / 한양의대학술지

Rheumatoid arthritis (RA) is a common autoimmune disease of unknown etiology characterized by symmetric and erosive synovitis. The course of RA is usually chronic and progressive, so it can result destructive joint damages. Nonsteroidal anti-inflammatory drugs, disease modifying anti-rheumatic drugs (DM ARDs) and low-dose corticosteroid have been used for the treatments of RA. The importance of early usage of DMARDs are stressed recently, however, the effects of DMARDs on long-term prognosis is not convincing. Since 1998, several biologic agents were developed for RA and showed promising results. These agents include TNF-alpha blockers such as etanercept, infliximab, adalimumab, and IL-1 receptor antagonist such as anakinra. Clinical studies for rituximab, anti-IL-6 receptor monoclonal antibody, and CTLA4-Ig are underway. The biologic agents show rapid improvement in clinical and laboratory parameters and may prevent the erosions on Xray, but because of costs and unknown long-term side effects, we should be more careful for using these drugs.