Successful Treatment of ANCA-Negative Wegener's Granulomatosis with Rituximab.

Wegener's Granulomatosis (WG) is a systemic vasculitis typically associated with antineutrophil cytoplasmic antibodies (ANCAs). A small proportion of patients are ANCA negative, however, and this is more commonly found in individuals with disease limited to the ears, nose, throat, and lungs, who do not have renal involvement. Rituximab is a monoclonal anti-CD20 antibody that has been demonstrated to be effective in the treatment of autoantibody-associated rheumatic diseases, including systemic WG. We report the case of a patient with ANCA-negative WG who responded well to rituximab, illustrating that even in the absence of detectable autoantibodies, B-cell depletion can be effective.

Benefits 8 years after a remission induction regime with an infliximab and methotrexate combination in early rheumatoid arthritis.

OBJECTIVE: To ascertain whether a 1-year remission induction therapy with an infliximab-MTX (INF-MTX) combination in patients with early RA provided sustained benefit after INF cessation compared with conventional treatment. METHODS: Twenty patients with poor prognosis RA of < 1 year of disease duration were randomized to receive either INF and MTX or placebo infusions and MTX for 1 year. They then stepped down to MTX monotherapy and were treated according to standard clinical care. After 8 years, disease activity, function and quality of life (QoL) data were collected. RESULTS: At follow-up, data were available for 18 patients (1 in each group had died). Median 28-joint DAS was significantly lower in the INF-MTX group compared with placebo-MTX group (2.7 vs 4.3, P = 0.02). Four patients in the INF-MTX group were in remission vs none in the placebo-MTX group. One patient in the INF-MTX group achieved drug-free remission. Both RAQoL and HAQ median scores were lower in the INF-MTX group; however, this did not reach statistical significance (median RAQoL 3 vs 8, P = 0.18; median HAQ 1.0 vs 1.5, P = 0.12). CONCLUSION: A remission induction regime with an INF-MTX combination for 1 year in early RA can improve long-term clinical outcomes. Larger studies will be required to confirm the implications of these findings.

Response to intramuscular methyl prednisolone in inflammatory hand pain: evidence for a targeted clinical, ultrasonographic and therapeutic approach.

BACKGROUND: Hand pain with stiffness is a common clinical presentation to early arthritis clinics, with outcome varying from resolution to the development of rheumatoid arthritis. OBJECTIVE: To assess the response and predictors of response to intramuscular methylprednisolone (MP) and hydroxychloroquine (HCQ) using a standardised treatment protocol. METHODS: Patients with inflammatory hand pain (IHP), defined as predominantly hand pain and morning stiffness of at least 30 min duration, received a standardised assessment prior to receiving intramuscular MP. Response (primary outcome) at 4 weeks was a 50% improvement in symptoms as perceived by the patient; responders who relapsed received repeat intramuscular MP and HCQ. RESULTS: 102 patients were recruited, of which 21% were rheumatoid factor (RF) positive, 23% had clinical synovitis, 25% had raised C-reactive protein level and 55% had ultrasound-detected synovitis. 73% responded, with associated significant reductions in morning stiffness, Health Assessment Questionnaire, painful and tender joint counts, and visual analogue scores (p < or = 0.006 for all). Ultrasound-detected synovitis (p<0.001) and RF (p = 0.04), but not clinical synovitis (p = 0.74), were significantly associated with response to intramuscular MP. 86% who remained on HCQ long term reported a benefit. CONCLUSIONS: Patients with IHP have significant improvement in symptoms and function following intramuscular MP. Further placebo-controlled trials are required to assess the role of intramuscular MP and ultrasonography in managing this patient group.

The evidence for early intervention.

It is believed that rheumatoid arthritis (RA) is the most common, potentially treatable cause of disability in the Western world. A commonsense approach to the management of a persistent, progressive, damaging condition such as RA would seem to be intervention before the onset of damage, at a stage when disease still may be reversible. Such a phase of disease has been described as a "window of opportunity" for intervention. This article discusses the evidence for early intervention in RA.

Potential for altering rheumatoid arthritis outcome.

The potential for disproportionately altering outcome in the early stages of rheumatoid arthritis (RA) was first hypothesized in the early 1990s. This window of opportunity hypothesis for therapeutic intervention in RA is based on the existence of a time frame within which there is a potential for a greater response to therapy, resulting in sustained benefits or, perhaps most important, a chance of cure. Given the persistent, progressive, damaging, inflammatory nature of RA, this approach to altering outcome in the early stages seems attractive.

Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12-month double-blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poor-prognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months. METHODS: All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months. RESULTS: Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C-reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between-group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05). CONCLUSION: Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.

Are early arthritis clinics necessary?

Landmark studies published in the 1980s were the first to reveal the long-term consequences of rheumatoid arthritis (RA). Instead of the benign outcomes previously reported from early population studies, disability, deformity and excess mortality were evident. At this time, the conventional pyramid approach was the standard for therapeutic intervention. Patients were initially treated with non-steroidal anti-inflammatory drug with rest and splinting a approach. Disease-modifying anti-rheumatic drugs and corticosteroids were reserved for patients with joint damage and disability, who had 'earned their treatment' and the perceived risk of toxicity. Thus irreversible damage and disability occurred prior to effective therapy being instituted, with the consequences of poor outcomes. The late 1980s saw the introduction of the concept of early intervention in RA and, shortly after, the introduction of specialist clinics for early assessment of patients with inflammatory arthritis (IA), so-called 'early arthritis clinics' (EACs). Such clinics, initially in large research units, targeted patients with early RA or IA with the potential to evolve to RA, with the aim of early case definition and treatment. After all, the common sense approach to treatment of a chronic inflammatory, destructive condition would be to treat it effectively from its onset, prior to the development of irreversible damage. The detailed documentation undertaken in these clinics subsequently provided much information regarding persistence and prognosis in early IA. Since their initial introduction, EACs have become commonplace, not only in academic units, but also kas part of clinical service provision in many institutions. This review details what an EAC is, who should be referred and when, and the benefits and potential future benefits of their introduction.

Prognostic factors in a large cohort of patients with early undifferentiated inflammatory arthritis after application of a structured management protocol.

OBJECTIVE: Inflammatory arthritis of the hands is a frequent clinical presentation with a variable outcome. Patients not satisfying the classification criteria for recognized arthritides are described as having undifferentiated inflammatory arthritis, for which there are no accepted therapeutic algorithms. This study assessed the clinical outcome of patients with undifferentiated arthritis of the hands after use of a treatment algorithm, and evaluated the prognostic features in these patients. METHODS: One hundred consecutive patients with undifferentiated arthritis of the hands were assessed following use of a pragmatic treatment algorithm that was based on clinical presentation and response to treatment. The following standard step-up treatment protocol was used: 1) nonsteroidal antiinflammatory drugs (NSAIDs), 2) a single dose of corticosteroid administered by either intramuscular or intraarticular injection, and 3) disease-modifying antirheumatic drugs (DMARDs). Patients with specific rheumatologic diagnoses were excluded. The primary outcome was persistence of synovitis at 12 months. RESULTS: Seventy-eight percent of patients received NSAIDs, 72% received corticosteroids, and 30% received DMARD therapy. Among patients who had synovitis at 12 months, the prevalence of rheumatoid factor (RF) seropositivity, swollen joints, and synovitis at baseline was greater than in those without persistent synovitis. Logistic regression analysis showed baseline investigations to be poor predictors of subsequent DMARD use, with the best predictor being persistence of synovitis at 12 weeks. Rheumatoid arthritis (RA) developed in 14 patients. Logistic regression analysis showed that significant predictors of RA were RF seropositivity and the painful joint count at baseline. No patient who experienced resolution of synovitis by 12 weeks had persistent synovitis that subsequently required DMARD therapy. Only 13% of patients entered remission. Early resolution of synovitis was associated with an excellent prognosis. CONCLUSION: Undifferentiated arthritis of the hands is not a benign condition, with 30% of patients receiving DMARD therapy by 12 months and low remission rates. Results of the clinical assessment at 12 weeks is the single best predictor of future therapy. This study provides background data for use in determining future therapeutic interventions.

Anti-tumor necrosis factor-alpha therapy-induced vasculitis: case series.

As experience with anti-tumor necrosis factor (TNF-alpha) therapy increases, there has been the expected emergence of reports on uncommon side effects. Large clinical trials identified the development of autoantibodies and postmarketing surveillance has identified problems including tuberculosis. There have been several case reports of drug-induced systemic lupus erythematosus. We describe eight patients with rheumatoid arthritis treated with anti-TNF therapies who developed presumed vasculitis, with different pathophysiologic causes. We discuss the literature and potential causal mechanisms, including disease activity, the role of autoantibodies, and shifts in T cell responses.