Canakinumab Lacks Efficacy in Treating Adult Patients with Moderate to Severe Chronic Spontaneous Urticaria in a Phase II Randomized Double-Blind Placebo-Controlled Single-Center Study.

BACKGROUND: Chronic idiopathic/spontaneous urticaria (CSU) is a common disease with a significant proportion of patients who do not respond to standard therapy with antihistamines and optionally corticosteroids/immunosuppressants. OBJECTIVE: The IL-1ß antagonist canakinumab is effective in cryopyrin-associated periodic syndromes associated with urticarial symptoms and urticarial vasculitis, and so it was suspected that it could also be effective in patients with CSU. METHODS: The effect of canakinumab was investigated in 20 patients with moderate to severe CSU in a 1:1 randomization to either canakinumab or placebo in a double-blind single-dose crossover design. The verum group received 150 mg canakinumab subcutaneously once at baseline. Patients who had received placebo were able to switch to canakinumab at week 4 if they did not improve. The primary end point was clinical improvement at week 4 compared with baseline in sum of urticaria activity scores over 7 consecutive days. Secondary end points were the clinical improvement at week 8 compared with baseline in sum of urticaria activity scores over 7 consecutive days and the clinical improvement measured by the Physician Score and Dermatology Life Quality Index at week 1, 2, 4, and 8. RESULTS: At week 4, 2 patients with canakinumab and 3 with placebo met the primary end point, and so canakinumab failed the significant superiority to the placebo (P = 1.0). An inclusion of the patients who switched to canakinumab after 4 weeks did not alter the result. There was also no significant difference between the verum and placebo groups for all secondary end points. The therapy was well tolerated, and mild adverse events were equally distributed between verum and placebo groups. CONCLUSIONS: Because of this clinical trial with 20 patients, it must be assumed that canakinumab has no effect on lesions of CSU. This suggests that IL-1ß may not play a crucial role in pathology of patients with CSU, unlike, for example, in hereditary fevers or urticarial vasculitis, where targeting IL-1 is a main treatment option. However, the good tolerability of canakinumab could be confirmed.

Efficacy of Omalizumab in Mastocytosis: Allusive Indication Obtained from a Prospective, Double-Blind, Multicenter Study (XOLMA Study).

BACKGROUND: Patients with mastocytosis often suffer from a variety of symptoms caused by mast cell mediators where treatments remain difficult, showing various success rates. Omalizumab, a monoclonal anti-IgE antibody, has been postulated to have a positive impact on mastocytosis-associated symptoms such as flush, vertigo, gastrointestinal problems, or anaphylaxis. OBJECTIVE: To investigate the efficacy and safety of omalizumab in systemic mastocytosis. METHODS: Patients with histologically proven mastocytosis were investigated in a multicenter prospective double-blind placebo-controlled trial to receive either omalizumab or placebo, dosed according to IgE and body weight. The primary endpoint was change in the AFIRMM activity score after 6 months of treatment. Different laboratory parameters were analyzed. RESULTS: Sixteen patients were analyzed: 7 to omalizumab and 9 to placebo (mean age 47.7 ± 13.8 vs. 45.4 ± 8.8 years; 66.6 vs. 85.7% were female; mean disease duration 10.0 ± 5.1 vs. 4.5 ± 2.9 years, respectively). After 6 months the median AFIRMM score decreased 50% from 52.0 to 26.0 in the omalizumab group versus 104.0-102.0 in the placebo group (p = 0.286); however, the difference was not significant (p = 0.941). Secondary endpoints, including the number of allergic reactions, changes in major complaints, wheal-and-flare reaction due to mechanical irritation (Darier's sign), and frequency of the use of mastocytosis-specific drugs improved in the omalizumab group, but not significantly. Adverse events like urticaria, bronchospasm, and anaphylactic shock showed no significant difference between the groups. No severe adverse events occurred. FcεRI (Fc-epsilon receptor) expression on basophils decreased after receiving omalizumab versus placebo. CONCLUSION: Omalizumab was safe and showed a tendency to improve mastocytosis-related symptoms, in particular diarrhea, dizziness, flush, and anaphylactic reactions, including the AFIRMM score and secondary endpoints; however, the difference was not significant. Due to the small study size and difference at baseline between the study groups, further studies are required to confirm our findings.

[Systemic sclerosis]. / Systemische Sklerose/Sklerodermie.

Systemic sclerosis (SSc) is a severe fibrotic multiorgan connective tissue disease. Vascular abnormalities such as fingertip ulcers and Raynaud's syndrome as well as involvement of organs including the lungs, heart, kidney and the gastrointestinal tract are prominent features of the disease. There are currently no disease modifying drugs available that can modify the course of the disease. In this review we will discuss medications that have been found to be effective in improving specific organ involvement due to SSc. For the treatment of gastroesophageal reflux disease (GERD), proton pump inhibitors are effective agents. In the setting of clinically significant gastrointestinal dysmotility, metoclopramide, erythromycin and octreotide may be beneficial. Small bowel bacterial overgrowth should be treated with oral antibiotics. Angiotensin converting enzyme inhibitors are the first-line agents for acute renal crisis. A variety of treatment options are available for Raynaud's phenomenon and include calcium channel blockers, iloprost (i. v.), losartan, fluoxetine and sildenafil. Fingertip ulcers can be prevented by using the endothelin receptor antagonist bosentan. The therapeutic options for treatment of pulmonary hypertension associated with SSc include bosentan, sildenafil and various prostacyclin analogs (eg, epoprostenol, treprostinil, iloprost). Sitaxentan, ambrisentan and new phosphodiesterase-5 inhibitors could be new options for therapy as well. Therapeutic options for interstitial lung fibrosis include cyclophosphamide, however, clinical effects are mild to moderate. Methotrexate has been used to treat skin fibrosis and can be beneficial when arthritis is present.

Successful use of vacuum-assisted closure therapy for leg ulcers caused by occluding vasculopathy and inflammatory vascular diseases--a case series.

BACKGROUND: Leg ulcers caused by vasculitis, small vessel occlusion or other rare conditions often prove to be very difficult to treat. Despite polypragmatic, systemic and localized therapy, many of these wounds are progressive and characterized by severe pain. METHODS AND RESULTS: We here portray the cases of 5 patients with ulcers resistant to systemic therapy for the underlying disease, who were treated successfully using vacuum-assisted closure (VAC) for wound management. We present the advantages and disadvantages of this method, as well as illustrating the essential and known therapeutic principles. CONCLUSIONS: Our experience shows VAC to be an excellent and effective alternative in the treatment of therapy-resistant chronic wounds caused by vasculopathy (small vessel occlusion or vasculitis). We did not observe any pathergy or proinflammatory effects caused by VAC.