Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: findings from the LIBERATE study.

BACKGROUND: Apremilast, an oral phosphodiesterase-4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis. OBJECTIVE: To evaluate long-term efficacy and safety of apremilast in biologic-naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial. METHODS: Two hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and Severity Index (PASI; 0-72), Scalp Physician Global Assessment (ScPGA; 0-5) and Nail Psoriasis Severity Index (NAPSI; 0-8); patient-reported outcomes (PROs) were assessed using the Dermatology Life Quality Index (DLQI; 0-32) and pruritus visual analog scale (VAS; 0-100 mm). RESULTS: The apremilast-extension phase (Weeks 16-104) included 226 patients in the placebo/apremilast (n = 73), apremilast/apremilast (n = 74) and etanercept/apremilast (n = 79) groups, and at Week 104, 50.7%, 45.9% and 51.9% of these patients, respectively, maintained ≥75% reduction from baseline in PASI score (based on last-observation-carried-forward analysis). Across treatment groups, ScPGA 0 (clear) or 1 (minimal) was achieved by 50.0%-59.2% of patients; NAPSI mean change from baseline was -48.1% to -51.1%; DLQI score ≤5 was achieved by 66.0%-72.5% of patients; and pruritus VAS mean change from baseline was -24.4 to -32.3. AEs in ≥5% of patients (diarrhoea, nausea, nasopharyngitis, upper respiratory tract infection and headache) did not increase with prolonged apremilast exposure. CONCLUSIONS: Apremilast demonstrated significant and sustained improvements in skin, scalp, nails and PROs (pruritus and quality of life) over 104 weeks in patients with moderate to severe plaque psoriasis. Safety was consistent with the known safety profile of apremilast.

Effect of resistance training on lumbar extension strength.

Development of a new testing machine, which stabilizes the pelvis, allowed us to evaluate the lumbar extensor muscles before and after training. Fifteen healthy subjects (29.1 +/- 8 years of age) trained 1 day per week for 10 weeks and 10 healthy subjects (33.7 +/- 16 years of age) acted as controls. Training consisted of 6 to 15 repetitions of full range of motion variable resistance lumbar extension exercise to volitional fatigue and periodic maximal isometric contractions taken at seven angles through a full range of motion. Before and after the 10 week training period, subjects completed a maximum isometric strength test at seven angles through a 72 degrees range of motion (0 degrees, 12 degrees, 24 degrees, 36 degrees, 48 degrees, 60 degrees, and 72 degrees of lumbar flexion). The training group significantly improved in lumbar extension strength at all angles (P less than or equal to 0.01). The result at 0 degrees (full extension) showed an increase from 180.0 +/- 25 Nm to 364.1 +/- 43 Nm (+102%) and at 72 degrees (full flexion) from 427.4 +/- 44.1 to 607.4 +/- 68 (+42%) Nm. Results from the control group showed no change (P greater than or equal to 0.05). The magnitude of gain shown by the training group reflects the low initial trained state of the lumbar extensor muscles. These data indicate that when the lumbar area is isolated through pelvic stabilization, the isolated lumbar extensor muscles show an abnormally large potential for strength increase.

Frequency and volume of resistance training: effect on cervical extension strength.

Quantification of cervical extension (CERV EXT) strength is complicated by the inability to stabilize the torso and isolate the CERV EXT muscles. A newly developed machine designed to stabilize the torso and isolate the CERV EXT muscles was used to evaluate the effect of frequency and volume of resistance training on CERV EXT strength. Fifty men (age, 26 +/- 9 years; height, 174 +/- 16 cm; weight, 74 +/- 9 kg) and 28 women (age, 30 +/- 9 years; height, 152 +/- 32 cm; weight, 62 +/- 7 kg) volunteered to participate. Subjects were randomly stratified to one of four training groups or a control group (CONT, n = 19) that did not train. Each training group exercised for 12 weeks as follows; once per week using one set of dynamic exercise (DYN 1x/wk, n = 14), once per week using one set of DYN and one set of maximal isometric (IM) exercise at eight angles through a 126 degrees-range of CERV EXT (DYN-IM 1x/wk, n = 16), DYN 2x/wk (n = 19), or DYN-IM 2x/wk (n = 10). Maximal IM torque was measured at eight angles initially and after 12 weeks of training. All training groups improved CERV EXT strength (p < or = 0.05) at all angles tested compared to the CONT except for DYN once per week at 0 degree of CERV flexion. A greater increase in strength was found when the groups that trained two times a week were compared to those that trained once per week.(ABSTRACT TRUNCATED AT 250 WORDS)

Pelvic stabilization during resistance training: its effect on the development of lumbar extension strength.

The purpose of this study was to evaluate and compare resistance exercise training with and without pelvic stabilization on the development of isolated lumbar extension strength. Isometric torque of the isolated lumbar extensor muscles was measured at seven positions through a 72 degree range-of-motion on 47 men and 30 women before and after 12 weeks of variable resistance lumbar extension training. Subjects were assigned to either a group that trained with pelvic stabilization (P-STAB, n = 21), a group that trained without pelvic stabilization (NO-STAB, n = 41), or a control group that did not train (n = 15). Subjects trained once a week with 8 to 12 repetitions to volitional exhaustion. The P-STAB and NO-STAB groups showed significant (p < or = 0.05) and similar increases in the weight load used for training (P-STAB = 24.1 +/- 9.4kg; NO-STAB = 19.4 +/- 11.0kg) during the 12-week training period. In contrast, posttraining isometric torque values describing isolated lumbar extension strength improved only for the P-STAB group (23.5%, p < or = 0.05) and not for the NO-STAB group (-1.2%, p > 0.05) relative to controls. These data indicate that pelvic stabilization is required to effectively train the lumbar extensor muscles. The increased training load for the NO-STAB group is probably the result of exercising the muscles involved in pelvic rotation (hamstring and buttock muscles).