Entecavir plus tenofovir combination therapy for chronic hepatitis B in patients with previous nucleos(t)ide treatment failure.

BACKGROUND AND AIMS: In patients with chronic hepatitis B (CHB) who have failed on other nucleos(t)ide analogs (NUCs), the combination of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single rescue regimen. METHODS: In this single-arm, open-label study, 92 CHB patients with a primary non-response, partial response, or virologic breakthrough on their current NUC were switched to ETV (1 mg) plus TDF (300 mg) and treated for 96 weeks. RESULTS: At baseline, 62 % of patients were HBeAg(+) and mean HBV DNA was 4.4 log10IU/mL. Patients had received ≥1 line of prior NUC therapy, with the latest regimen consisting of monotherapy with ETV (53 %), lamivudine (LVD 22 %), TDF (12 %), adefovir (ADV 4 %), or telbivudine (2 %), or combinations of these agents (7 %); 58 % had evidence of single- or multidrug resistance mutations (LVD 52 %, ETV 26 %; ADV 7 %). Response rates for HBV DNA <50 IU/mL were 76 % (70/92) at week 48 (primary endpoint), and 85 % (78/92) at week 96, including 80 % (16/20) in prior LVD failures, 100 % (4/4) in ADV failures, 82 % (9/11) in TDF failures, and 88 % (42/48) in ETV failures. No treatment-emergent resistance to ETV or ADV was observed. ETV/TDF was well tolerated, with no significant renal or additive toxicities observed. CONCLUSIONS: In NUC-experienced patients who have failed prior NUC therapy, ETV/TDF was well tolerated and effective, achieving virologic suppression through 96 weeks in the majority (85 %), irrespective of prior NUC exposure, without occurrence of treatment-emergent resistance to either agent.

Comparative safety and efficacy of two formulations of mometasone nasal spray in adult seasonal allergic rhinitis.

Mometasone furoate as a nasal spray is an effective treatment for seasonal allergic rhinitis (SAR). An aqueous mometasone nasal spray containing the same active substance and excipients as the originator product (reference mometasone) has been developed. This study was designed to establish therapeutic equivalence of test mometasone to reference mometasone and superiority over placebo for the treatment of SAR in adults. In this multicenter, randomized, double-blind, placebo- and active-controlled, fixed-dose study, patients aged ≥18 years with SAR were randomized 2:2:1 to reference mometasone, test mometasone, or placebo for 28 days. Patients recorded nasal and ocular symptoms daily. The primary end point was change from baseline in the pooled 24-hour reflective total nasal symptom score (rTNSS). Safety and tolerability included evaluation by adverse events (AEs), physical (including nasal) examinations, vital signs assessments, laboratory evaluations, and change in concomitant medications. Four hundred two patients received reference mometasone (n = 156), test mometasone (n = 163), or placebo (n = 83). The intent-to-treat population (ITT) comprised 399 patients, and the per-protocol (PP) population comprised 327 patients. The 95% confidence intervals for the treatment difference (reference minus test mometasone) in change from baseline in pooled 24-hour rTNSS were within prespecified equivalence limits for the PP and ITT populations. Both active treatments showed superiority over placebo (p = 0.0019-0.0087). No significant difference was seen between test mometasone and reference mometasone for any secondary efficacy variables. Treatment-emergent AE incidence was low. No deaths or serious AEs were reported. The test mometasone is efficacious in the treatment of SAR in adults and shows a favorable safety profile. The results indicate that the test mometasone is therapeutically equivalent to the reference mometasone.