Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

Background Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. Methods In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. Results In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. Conclusions Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.

Flutamide-induced acute renal failure in a patient with metastatic prostate cancer

Androgen blockage, with either orchiectomy or luteinizing hormone releasing hormone (LHRH) analogs combined with an antiandrogen drug, is the standard treatment for metastatic prostate cancer. Flutatr ide is a nonsteroidal antiandrogen drug that is frequently used for total androgen blockage. We report on a 54-yr-old man with metastatic prostate cancer who developed nonoliguric acute renal failure (ARF) during treatment with flutamide. Following discontinuation of flutamide therapy, his renal functions returned to normal limits within 4 wk. After a rechallenge with flutamide, serum levels of BUN and creatinine increased again. His renal function recovered completely after the cessation of the drug for the second time. This observation confirm that ARF may be clearly attributed to flutamide therapy. Although very rare, flutamide-induced ARF should be considered

Persisting fever in a patient with brucella endocarditis: occult splenic abscess

Brucella endocarditis, despite its high mortality rate with combined medical and surgical treatment, has a low occurrence rate in cases of brucellosis and has been endemic in regions surrounding Turkey. Rarely, patients with infective endocarditis with common microorganisms develop a splenic abscess. A patient is reported on with brucella endocarditis and persistent fever. An occult splenic abscess was found. This is the second reported case in the literature of brucella endocarditis with splenic abscess

arthritis and spondyloarthropathy on hemodialysis

We aimed to evaluate the efficacy and safety of long-term use of etanercept therapy in patients with spondyloarthropathy (SpA) and rheumatoid arthritis (RA) on hemodialysis (HD). Selected RA or SpA patients treated with etanercept under HD were retrospectively evaluated. Etanercept-related adverse events were closely recorded for all patients. At the follow-up, erythrocyte sedimentation rate and C-reactive protein levels were monitored. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for SpA patients and Disease Activity Score (DAS28) for RA patients were measured at every 3 or 6 months. In total five end-stage renal disease (ESRD) patients were enrolled to the study. The causes of ESRD in the study subjects were amyloidosis (n=2), analgesic nephropathy (n=2), and nephrolithiasis (n=1). Three were diagnosed as SpA and two were RA. All patients used etanercept. The median age was 39 years (range 22-72 years). The median disease duration was 12 years (range 2-20 years). The median follow-up after etanercept therapy was 18 months (range 5-33 months). DAS28 score decreased after the treatment and did not increase during follow-up in RA patients. BASDAI score decreased after the treatment during follow-up in three patients with SpA. At the follow-up, only one patient was diagnosed with septic arthritis. As a result of our study, etanercept treatment in RA and SpA patients on HD seems to be safe, well tolerated, and effective in most of the patients. Above all, due to impaired host defense in patients with ESRD, enhanced risk of infections should be kept in mind during follow-up period and larger trials are needed to prove the safety of etanercept in HD patients