Rituximab for Rheumatoid Arthritis.

Rituximab is a chimeric monoclonal antibody directed at the CD20 molecule on the surfaces of some but not all B cells. It depletes almost all peripheral B cells, but other niches of B cells are variably depleted, including synovium. Its mechanism of action in rheumatoid arthritis (RA) is only partially understood. Rituximab was efficacious in clinical trials of patients with RA, including those who are methotrexate naïve, those with an incomplete response to methotrexate, and those with an incomplete response to tumor necrosis factor inhibitors. The need for a concomitant traditional disease-modifying drug, the optimal dose of rituximab, and the optimal interval for retreatment remain somewhat uncertain. Rituximab seems to be most efficacious in seropositive patients and those with an incomplete response to only one tumor necrosis factor inhibitor. Rituximab has a reasonable safety profile, with a small risk of serious infectious events, which is stable over time and repeat courses. Opportunistic infections are rare. Reactivation of hepatitis B remains a concern. The possible association of rituximab and progressive multifocal leukoencephalopathy may still require vigilance. Malignancies and cardiovascular events do not appear to be increased. Infusion reactions are more likely with the initial infusion, and are usually mild. Rituximab may cause hypogammaglobulinemia, but any risk of subsequent risk of increased infectious events is not yet well established. Before initiating rituximab, patient screening for hypersensitivity to murine proteins, infections, congestive heart failure, pregnancy, and hypogammaglobulinemia is imperative. Vaccinations should be administered prior to treatment whenever possible. Rituximab has been a significant addition to the rheumatologists' armamentarium for the treatment of RA.

Eosinophilic fasciitis: clinical characteristics and response to methotrexate.

AIM: To describe our experience with 16 patients with eosinophilic fasciitis (EF) treated in our clinic over 14 years. METHODS: We retrospectively reviewed the charts of all patients with biopsy-proven EF. We collected data regarding demographics, clinical presentations, possible triggers, labs, imaging, treatment and response to therapy on follow-up. RESULTS: Eight women and eight men with a mean age of 52 years were included in the study. Three patients related the onset to prior strenuous exercise and one was exposed to vibratory machinery. Fourteen patients had a gradual onset and presented with induration of the skin. Two other patients presented with acute-onset and significant edema and weight gain. All patients required immunosuppressive therapy. Methotrexate (MTX) was used in all of our patients. The rate of complete remission was ~60%. Although the recurrence rate after stopping MTX was 70%, these patients responded well to re-treatment with MTX. CONCLUSION: We believe that MTX represents an effective treatment option for EF. The rarity of this disease would make a double-blind controlled trial study difficult to perform.

Factors associated with radiographic progression in patients with rheumatoid arthritis who were treated with methotrexate.

OBJECTIVE: To identify factors associated with radiographic progression at 52 weeks in patients with rheumatoid arthritis (RA) after 12 weeks of methotrexate (MTX) therapy. METHODS: The study population consisted of patients from the MTX arm of the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO). Logistic regression analysis was used to identify clinical and laboratory assessments performed at Week 12 of MTX therapy that might be associated with Week 52 radiographic outcome (modified total Sharp score). Classification and regression tree (CART) modeling of the Week 12 assessments was used to determine the subgroups of patients with the best and worst radiographic outcomes. RESULTS: A total of 169 patients were analyzed: 116 patients in the best radiographic outcome group and 53 patients in the worst radiographic outcome group. Logistic regression analysis showed that Week 12 C-reactive protein (CRP) level, erythrocyte sedimentation rate, tender joint count, swollen joint count (SJC), and Health Assessment Questionnaire scores were significantly associated with radiographic progression at Week 52 (p < 0.05 for each assessment). CART modeling showed that patients with Week 12 CRP > 0.67 mg/dl and SJC > 1 and patients with Week 12 CRP ≤ 0.67 mg/dl and SJC > 10 were likely to show the worst radiographic progression at Week 52. The CART model had a sensitivity of 85%, specificity of 60%, and overall classification accuracy of 68%. CONCLUSION: In patients with RA, measures of CRP and SJC after 12 weeks of MTX therapy emerged as the factors most associated with radiographic progression at Week 52.

Minor salivary gland biopsy to detect primary Sjogren syndrome in patients with interstitial lung disease.

PURPOSES: To describe a cohort of patients who presented with interstitial lung disease (ILD) of unknown cause, features of primary Sjögren syndrome (pSS), and a positive minor salivary gland biopsy (MSGB). METHODS: Thirty-eight patients with ILD evaluated at our center underwent an MSGB to confirm a diagnosis of pSS. All of the samples were reviewed by pathologists experienced in the evaluation of salivary gland histology. We defined a positive MSGB finding as a lymphocyte focus score of >1. RESULTS: At presentation, all patients had ILD, and symptoms of cough and dyspnea. None had a definable connective tissue disease (CTD) or known cause for their ILD. Thirteen patients (34%) had positive MSGB findings. Of these, the median age was 61 years (age range, 33 to 75 years); 7 patients (54%) were women; 8 patients (62%) had a smoking history; and 10 patients (77%) had sicca symptoms. In all patients, a thoracic high-resolution CT scan evaluation demonstrated bibasilar, peripheral-predominant, ground-glass, and reticular opacities. Four patients (31%) were negative for both antinuclear autoantibody (ANA) and rheumatoid factor (RF) autoantibody, and three patients (23%) were negative for ANA, RF, Sjögren syndrome (SS)-A, and SS-B autoantibodies. No patients experienced any complications from the MSGB. The identification of underlying pSS did not affect the management of ILD in these patients. CONCLUSIONS: Confirming a diagnosis of pSS-related ILD by performing MSGB allows for a more precise CTD classification. This study provides evidence that CTD may exist subclinically, and longitudinal studies are needed to determine whether identifying occult CTD impacts on management, longitudinal changes in lung function, or survival.

Unresolved issues in identifying and overcoming inadequate response in rheumatoid arthritis: weighing the evidence.

Rheumatoid arthritis (RA) is a chronic, multisystem, inflammatory disorder of the joints that affects about 1% of the world population. The ultimate goals of therapy include remission of disease and prevention of joint damage. Reaching these goals has become a realistic outcome for an increasing number of patients as treatment options have expanded over the past 3 decades. In addition to older therapies, such as methotrexate (MTX), other disease modifying drugs (DMARD), and tumor necrosis factor (TNF) inhibitors, newer biologic treatments have become available. For the substantial number of patients who experience an inadequate response to standard medications, biologic response modifiers (BRM) provide an important therapeutic alternative. The availability of multiple treatment options in the absence of clear definitions or criteria for remission and inadequate response, however, makes clinical decisions about measuring outcomes, predicting response to treatment, and prescribing pharmacologic therapies challenging. In this program, distinguished rheumatologists weigh the evolving body of clinical evidence to draw sound conclusions and resolve key issues in managing inadequate response to treatment and in achieving optimal outcomes in RA.

Longitudinal analysis of the use of etanercept versus infliximab determined from medical chart audit.

OBJECTIVE: To describe the dosing of etanercept and infliximab for the treatment of rheumatoid arthritis (RA). METHODS: Adult patients with a diagnosis of RA who were treated with either etanercept or infliximab between 1999 and 2002 were selected from 16 rheumatology practices in the western and southeastern United States. Patients with a terminal illness or those receiving a tumor necrosis factor (TNF)-alpha inhibitor for an indication other than RA were excluded. Data were collected through a review of the patient medical records. Data collected on each patient included demographics, concurrent disease-modifying antirheumatic drug therapy, TNF-alpha inhibitor dose, frequency, duration of TNF-alpha inhibitor therapy, and discontinuation of TNF-alpha inhibitor therapy. RESULTS: A total of 244 patients were included in the evaluation (etanercept only [n=128; 52%], infliximab only [n=89; 36%], both [n=27; 11%]). The mean age of these patients was 55.1+/-13.3 years, 54.9+/-13.5 years, and 52.8+/-14.0 years, respectively; the mean duration of RA was 13.3 +/- 8.8 years, 13.4+/-8.0 years, and 14.0 +/- 9.9 years, respectively. Female patients constituted 70% of the sample. Health maintenance organization insurance was the most common form of medical insurance (45.8%), followed by Medicare (22.3%). The mean duration of follow-up for etanercept and infliximab treatment was 29.3+/-14.1 months and 14.8+/-6.9 months, respectively. Among patients who were still receiving therapy at the time of review, the mean initial and last etanercept doses were 25.0 mg versus 25.8 mg (P=0.16); the mean initial and last infliximab doses were 3.38 mg/kg versus 4.51 mg/kg (P<0.001). CONCLUSION: The dosing of etanercept and infliximab therapy was consistent with the approved labeling of both medications.

The Churg Strauss syndrome (allergic granulomatous angiitis): review and update.

OBJECTIVES: Review the clinical and physiopathologic aspects of the Churg-Strauss syndrome (CSS), including recent data regarding treatment and possible etiologic and triggering factors. METHODS: A search of the Medline database was conducted between 1966 and 2002, regarding CSS and related vasculitic conditions. Original articles were reviewed as well as major vasculitis textbooks, which were also examined for original references. RESULTS: CSS has been increasingly recognized during the past few decades, but remains an uncommon disease of unknown cause. The disorder had been traditionally classified as a variant of polyarteritis nodosa until its updated description by Churg and Strauss in 1951. Although it shares various clinical laboratory and pathologic characteristics with polyarteritis nodosa and Wegener granulomatosis, a distinct combination of features makes it a separate entity. The presence of asthma, usually of adult onset, along with other allergic symptoms, peripheral and tissue eosinophilia, and systemic vasculitis should prompt the clinician to consider the diagnosis, seek potential confirmation with a tissue biopsy, and begin therapy to minimize complications and prevent permanent organ damage. The treatment of CSS has been mainly extrapolated from other vasculitides, and the literature addressing drug therapy for this specific syndrome is limited. CONCLUSIONS: CSS is a distinct entity that should be recognized and distinguished from other forms of vasculitis to provide the appropriate early treatment, which could prevent permanent organ damage.

Temporal artery bruits in a patient with giant cell arteritis.

Giant cell arteritis (GCA) is a disease of unknown etiology characterized by granulomatous inflammation of medium and large arteries. A 69-year-old man presented with right jaw claudication, intermittent scalp tenderness without headache, and visibly swollen temporal arteries. Results of a right temporal artery biopsy were positive for GCA. Auscultation revealed audible bruits of the temporal arteries. We believe this is the first reported example of bruits of the temporal arteries as a manifestation of GCA. The condition resolved with corticosteroid therapy.