Outcome of refractory to conventional and/or biologic treatment adult Still's disease following canakinumab treatment: Countrywide data in 50 patients.

OBJECTIVE: To assess the efficacy and safety of the IL-1b inhibitor canakinumab in all adults with refractory Still's disease identified from the National Organization For Medicines for off-label drug use. METHODS: In a retrospective longitudinal multicenter cohort of 50 patients (median age 39 years) with active Still's disease despite treatment with corticosteroids (n = 11), conventional and synthetic (n = 34) and/or biologic disease modifying anti-rheumatic drugs (n = 30), we assessed the efficacy of canakinumab 150-300 mg administered every 4 (n = 47) or 8 weeks (n = 3) as combination therapy or monotherapy (n = 7) during a median follow-up of 27 (3-84) months. RESULTS: Α complete response was initially observed in 78% of patients within 3 months (median), irrespective of age at disease onset. A partial response was evident in 20%. One patient had resistant disease. Treatment de-escalation was attempted in 15 of 39 complete responders and a complete drug discontinuation in 21 patients for 8 months (median). Eleven patients (22%) relapsed during treatment, one during de-escalation process, and 11 after treatment discontinuation. Overall, 9 of 11 relapses were successfully treated with canakinumab treatment intensification or re-introduction. At last visit, 18% of patients were off treatment due to remission and 26% due to disease activity. Canakinumab had a significant corticosteroid sparing effect allowing weaning in 21 of 41 cases. Infections (20%, severe 4%) and leucopenia (6%) led to treatment cessation in one patient. CONCLUSION: High rates of sustained remission were observed in this, largest so far, real-life cohort of adult patients with refractory Still's disease treated with canakinumab.

Successful response in a case of severe pustular psoriasis after interleukin-1ß inhibition.

Generalized pustular psoriasis (GPP) is a severe type of psoriasis accompanied by systemic and often life-threatening manifestations. The efficacy of the interleukin (IL)-1 antagonist anakinra in cases of GPP underscores the role of IL-1 in disease pathogenesis. We present a case of a middle-aged man who developed an abrupt and severe form of GPP with severe eosinophilia and cholestatic hepatitis. The patient received salvage treatment with a combination of glucocorticoids, hydroxyurea and imatinib, while administration of the IL-1 inhibitor anakinra resulted in remission of hepatitis and a significant skin improvement. However, due to persistent hypersensitivity skin reactions, anakinra was withdrawn and replaced with the anti-IL-1ß antagonist canakinumab. As a result of canakinumab, the patient's skin completely cleared, while no systemic manifestations recurred. After 1 year of continuous canakinumab therapy, the patient remained virtually free of symptoms, while the drug was well tolerated.

Certolizumab for rheumatoid arthritis.

This is a review of the pharmacology of certolizumab pegol and its efficacy and safety in the treatment of patients with rheumatoid arthritis refractory to synthetic disease-modifying anti-rheumatic drugs (DMARDs). Certolizumab is a new anti-TNF-α biologic agent injected subcutaneously with an innovative molecular structure and unique pharmacodynamic and pharmacokinetic properties. Data from controlled clinical trials indicate that the drug is effective in reducing disease activity and disability. It also inhibits radiographic progression. Certolizumab administration has an acceptable safety profile. The clinical data available suggest that the nature of adverse events is generally comparable to that of other TNF-α blockers. Given its rapid onset of action certolizumab presents an attractive alternative therapeutic option for patients with moderate to severe RA refractory to DMARDs.

Prognostic factors for erosive rheumatoid arthritis.

The course of rheumatoid arthritis (RA) varies among patients, ranging from a mild disease with a small impact on patient's functional capacity to a severe, erosive and catastrophic disease accompanied by subluxations, deformities and subsequent poor quality of life. In clinical practice, the prediction of the outcome of RA is substantial in terms of making the right therapeutic decision for each patient. Reliable prognostic factors of long-term outcome are needed, so as to distinguish patients prone to severe disease course from patients with a smaller probability of severe structural damage. For the former group early aggressive treatment is required, whereas in the latter group remission may be achieved with less aggressive and potentially less toxic treatments. In the present review, the predictive role of demographic, clinical, laboratory, imaging, immunological and genetic characteristics of RA patients is discussed.

A case of Brucella spondylitis in a patient with psoriatic arthritis receiving infliximab.

A 69-year-old woman with psoriatic arthritis treated with infliximab presented with low back pain of recent onset and fever. Serological, microbiological and imaging studies revealed Brucella spondylitis at the L5-S1 level. Immunosuppressive therapy was suspended and antibiotic therapy including doxycycline and rifampicin was administered for six months. The patient responded adequately with clinical and laboratory improvement and a considerable remission of spondylitis on repeat magnetic resonance imaging scan. The pathophysiology of tumor necrosis factor (TNF) alpha in Brucellosis and the role of anti-TNFalpha therapy are discussed.

Rheumatic-like syndrome as a symptom of underlying gastric cancer.

Several observations imply that atypical rheumatic manifestations may be associated with occult neoplasia. A 71-year-old woman was admitted to the hospital three times in 2 years. Initially, she was admitted for investigation of an iron-deficient anemia associated with upper intestinal tract symptoms. Endoscopy revealed hiatus hernia, esophagitis, and duodenal ulcer with a Helicobacter pylori infection, but there were no signs of malignancy, and the patient received appropriate drug treatment. Two years later, she presented with arthralgias concerning the upper and lower limbs in an asymmetrical distribution, low fever, and persistence of the anemia, despite the treatment she had received and the fact that her gastrointestinal symptoms had long ceased. Immunological assays showed no specific rheumatic disorder, and the patient was discharged after showing significant improvement with the use of COX-2 selective NSAIDs. Finally, 4 months later, she was readmitted with worsening of the arthralgias, arthritis in the right radiocarpal joint, and severe anemia. Hematemesis that occurred during her hospital stay led to an emergency endoscopy and the diagnosis of gastric adenocarcinoma. Only a few cases have been reported so far concerning rheumatic manifestations as signs of an occult gastric cancer. Thus, there must be some degree of suspicion when dealing with patients with anemia and rheumatic symptoms that cannot be classified into a particular rheumatologic entity, because they might conceal a gastrointestinal malignancy not yet evident.