Electropherogram demonstrating heterozygosity for a GrA missense mutation at nucleotide position 188 in exon 9 of TNNT3 in a family with DA2B. To confirm the presence of this mutation, we incorporated a MluI restriction site into the amplicon by mismatch PCR. The presence of the mutation eliminates this site, producing fragments of 144 bp and 110 bp in the affected mother and her two affected children (blackened symbols), whereas the unaffected father is homozygous for the 110-bp fragment.

Objective: Patients with somatic conditions, such as psoriasis, frequently suffer from high burden of their disease in daily life and might benefit from internet-based cognitive behavioral therapy (ICBT) tailored to their adjustment problems. The aim of this multicenter randomized controlled trial was to examine the effects of therapist-guided, individually tailored ICBT in a clinical sample of patients with psoriasis. Methods: A total of 131 patients with psoriasis, who were screened for a psychological risk profile, were randomized to either care as usual (CAU, n = 66) or ICBT in addition to CAU (n = 65). Participants filled out standardized self-report questionnaires assessing physical and psychological functioning and impact on daily activities at baseline, posttreatment assessment, and 6-month follow-up. Results: In covariate-controlled linear mixed-model analyses, significantly larger improvements in ICBT compared to CAU were found in the primary outcomes physical functioning (p = 0.03, d = 0.36) and impact on daily activities (p = 0.04, d = 0.35), but not in psychological functioning (p = 0.32), up to 6 months after treatment compared to baseline. In explorative analyses, the working alliance measured at the beginning of ICBT treatment predicted improved physical (p = 0.02) and psychological (p < 0.001) outcomes. Conclusions: Results underline the promise of therapist-guided, individually tailored ICBT to improve physical functioning and reduce the impact of psoriasis on daily activities in patients with a psychological risk profile. Establishing a good therapeutic relationship early on may be an important factor that influences treatment outcomes in personalized ICBT interventions. Further research is needed to evaluate ICBT effectiveness in additional samples and to explore its underlying mechanisms.

IMPORTANCE Biologics revolutionized the treatment of psoriasis. Biologics are given in a fixed dose, but lower doses might be possible. OBJECTIVE To investigate whether dose reduction (DR) of biologics in patients with stable psoriasis is noninferior to usual care (UC). DESIGN, SETTING, AND PARTICIPANTS This pragmatic, open-label, prospective, controlled, noninferiority randomized clinical trial was conducted from March 1, 2016, to July 22, 2018, at 6 dermatology departments in the Netherlands. A total of 120 patients with plaque psoriasis and stable low disease activity who were receiving treatment with adalimumab, etanercept, or ustekinumab were studied. INTERVENTIONS Patients were randomized 1:1 to DR (n = 60) or UC (n = 60). In the DR group, injection intervals were prolonged stepwise, leading to 67% and 50% of the original dose. MAIN OUTCOMES AND MEASURES The primary outcome was between-group difference in disease activity corrected for baseline at 12 months compared with the predefined noninferiority margin of 0.5. Secondary outcomes were Psoriasis Area and Severity Index (PASI) score and health-related quality of life (including Dermatology Life Quality Index [DLQI] and Medical Outcomes Study 36-Item Short Form Health Survey scores), proportion of patients with short and persistent flares (defined as PASI and/or DLQI scores >5 for Ն3 months), and proportion of patients with successful dose tapering. RESULTS Of 120 patients (mean [SD] age, 54.0 [13.2] years; 82 [68%] male), 2 patients were lost to follow-up, 2 patients had a protocol violation, and 5 patients had a protocol deviation, leaving 111 patients for the per-protocol analysis (53 in the DR group and 58 in the UC group). The median PASI scores at month 12 were 3.4 (interquartile range [IQR], 2.2-4.5) in the DR group and 2.1 (IQR, 0.6-3.6) in the UC group (mean difference, 1.2; 95% CI, 0.7-1.8). This indicates that noninferiority was not demonstrated for DR compared to UC. The median DLQI score at month 12 was 1.0 (IQR, 0.0-2.0) in the DR group and 0.0 (IQR, 0.0-2.0) in the UC group (mean difference, 0.8; 95% CI, 0.3-1.3), indicating noninferiority for DR compared with UC. No significant difference was found regarding persistent flares between groups (n = 5 in both groups). Twenty-eight patients (53%; 95% CI, 39%-67%) in the DR group tapered their dose successfully at 12 months. No severe adverse events related to the intervention occurred. CONCLUSIONS AND RELEVANCE In this trial, noninferiority was not demonstrated for DR of adalimumab, etanercept, and ustekinumab based on the PASI in patients with psoriasis compared with UC with the chosen noninferiority margin. However, the strategy was noninferior based on the DLQI. Dose tapering did not lead to persistent flares or safety issues.

Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be 'happy' in 79% of episodes and 'unhappy' in 21%. We introduced the new concept of 'happy' drug survival because the proportion of on-drug patients with good quality of life is an important indicator for treatment success.

Ustekinumab has the highest confounder-corrected long-term drug survival in psoriasis treatment, compared with adalimumab and etanercept. Higher BMI is a predictor for discontinuation due to ineffectiveness in etanercept and ustekinumab, and female sex is a consistent predictor for discontinuation due to side-effects in all three outpatient biologics.