Psoriasis affects patients both physically and psychologically.To investigate the effect of comorbidities on health-related quality of life (HRQoL) and to determine whether infliximab improved HRQoL in the presence of these conditions.In this multicentre, double-blind study, 835 patients with moderate-to-severe plaque psoriasis were randomized to receive infliximab 3 or 5 mg kg(-1) or placebo at weeks 0, 2 and 6. Infliximab-treated patients were re-randomized at week 14 to receive the same treatment every 8 weeks or as needed through week 46; placebo patients crossed over to infliximab 5 mg kg(-1) at week 16. Disease severity (Psoriasis Area and Severity Index, PASI) and HRQoL (Dermatology Life Quality Index, DLQI; 36-item Short-Form Health Survey, SF-36) were measured at various time points. The effect of patient comorbidities on baseline HRQoL was assessed using multiple regression models. The impact of key comorbidities on infliximab treatment effect was also assessed.Disease severity (PASI), depression and psoriatic arthritis (PsA) were predictors of poor baseline HRQoL. At week 10, infliximab 3 and 5 mg kg(-1) significantly improved physical and mental health dimensions of the SF-36 and the DLQI (all P < 0.001). Consistent improvement in HRQoL with infliximab treatment was observed regardless of baseline patient characteristics or comorbidities. Through week 50, HRQoL and PASI scores were most improved with infliximab 5 mg kg(-1) administered every 8 weeks.Disease severity, depression and PsA were significant predictors of poor HRQoL. Infliximab significantly improved HRQoL, regardless of these characteristics.
To examine the impact of ustekinumab (UST) treatment on patient reported outcomes in patients with active psoriatic arthritis (PsA) using week 24 data from two Phase 3 clinical studies, PSUMMIT I and II.
Methods
Adult patients with active PsA despite DMARD and/or NSAID therapy (PSUMMIT I, n=617) or previously treated with anti-TNFα therapy (PSUMMIT II, n=312) were randomized to receive UST 45mg, 90mg, or placebo (PBO) at wks 0, 4, and q12wks, thereafter. Patient reported outcomes were measured using the Health Assessment Questionnaire (HAQ), Dermatology Quality Life Index (DLQI), SF-36health survey questionnaire (SF-36), Visual Analogue Scales (VAS) for impact of PsA on work productivity (0-10), patient assessment of pain (0-10), and disease activity (0-10). Sub-analyses were conducted by combining both studies into 3 mutually exclusive groups based on treatment history: MTX naïve, previously treated with MTX therapy, and previously treated with anti-TNF therapy.
Results
At baseline, patients in both studies had moderate to severe physical disability and impaired health related quality of life with a mean HAQ score of ≥1.25, mean DLQI score of ≥10 and mean SF-36 PCS and MCS below 50 (normal population score). In PSUMMIT I, UST-treated patients achieved statistically significantly greater improvements in HAQ (- 0.31 and -0.4 vs. -0.1), DLQI (-6.6 and -7.5 vs. -1.4), and SF-36 PCS (4.9 and 6.2 vs. 1.4), for the UST 45mg, 90mg, vs. PBO groups, respectively. When compared to PBO, greater proportions of UST-treated patients achieved clinical meaningful improvements in HAQ (≥0.3) (47.8% and 47.5% vs. 28.2%), DLQI (≥5) (58.6% and 63.1% vs. 32.9%), and SF-36 PCS (≥5) (45.5%, and 53.3% vs. 26.0%), for the UST 45mg, 90mg, vs. PBO groups, respectively. Similar results were observed in PSUMMIT II and in the sub-analyses by MTX naïve, prior MTX experienced, and prior anti-TNFα experienced patients. Similar results were also observed in SF-36 sub-scales, especially in bodily pain and physical health. In the anti-TNF naïve population, statistically significantly greater improvement in SF-36 MCS was observed in the combined UST 45mg and 90mg group vs PBO Additionally, UST-treated patients achieved statistically significantly greater improvements in patient assessment of pain, patient assessment of disease activity, and greater reduction in impact of disease on work productivity vs PBO-treated patients.
Conclusions
UST improves physical function, improves general, arthritis and skin-related quality of life, and reduces the impact of disease on work productivity in patients with active PsA regardless of current or prior MTX use or prior anti-TNF experience.
Disclosure of Interest
P. Rahman Grant/research support from: Janssen R&D, LLC, L. Puig Grant/research support from: Janssen R&D, LLC, A. Gottlieb Grant/research support from: Janssen R&D, LLC, A. Kavanaugh Grant/research support from: Janssen R&D, LLC, I. McInnes Grant/research support from: Janssen R&D, LLC, C. Ritchlin Grant/research support from: Janssen R&D, LLC, S. Li Shareholder of: Johnson& Johnson, Employee of: Janssen R&D, LLC, Y. Wang Shareholder of: Johnson& Johnson, Employee of: Janssen R&D, LLC, N. Zhao Shareholder of: Johnson& Johnson, Employee of: Janssen Global Services, LLC, R. Ganguly Shareholder of: Johnson& Johnson, Employee of: Janssen Global Services, LLC, M. Song Shareholder of: Johnson& Johnson, Employee of: Janssen R&D, LLC, C. Han Shareholder of: Johnson& Johnson, Employee of: Janssen Global Services, LLC
In the placebo (PBO)-controlled Phase III aSTRAEA study (ClinicalTrials.gov, NCT01860976) in psoriatic arthritis (PsA), abatacept (ABA) 125 mg SC weekly significantly increased the aCR20 response rate at Week 24 versus PBO (39.4% vs 22.3%, respectively; p<0.001; primary endpoint).1 Numerical benefits in physical function, enthesitis and dactylitis and a modest impact on psoriasis lesions were also seen at Week 24. Efficacy was maintained or improved up to Week 52.1
Objectives
To assess aBA safety up to 2 years in patients (pts) enrolled in aSTRAEA.
Methods
Pts with active PsA were randomised 1:1 to aBA or PBO for 24 weeks followed by 28 weeks' open-label (OL) aBA (total time on study: 52 weeks); pts without ≥20% improvement in joint counts at Week 16 (early escape) were switched to OL aBA (total time on study: 44 weeks).1 Pts could subsequently receive OL aBA in a 52-week long-term extension (LTE; Year 2) for the collection of safety data. The proportions of pts in the cumulative aBA population (all pts who received ≥1 dose of aBA at any time in the study) with aEs (all aEs, serious aEs [SAEs], deaths, aEs leading to discontinuation), laboratory marked abnormalities and anti-ABA antibodies over the cumulative aBA period (date of first treatment dose to end of LTE) were recorded in 1-year and 6-month intervals.
Results
Overall, 398 pts were included in the analysis of the cumulative aBA period (213 received aBA from study Day 1; 185 completed initial randomisation to PBO and received aBA thereafter). Of these, 322 pts entered the LTE (initial randomisation: aBA, n=162; PBO, n=160) and continued to receive OL aBA beyond the 28-week OL period. Of 162 and 160 pts initially randomised to aBA and PBO, respectively, 19 (11.7%) and 21 (13.1%) pts discontinued aBA in the LTE. Median (range) number of aBA injections in the cumulative aBA period to end of LTE was 80 (1–133). Safety during the cumulative aBA period over 2 years is shown (Table 1); 6-month interval safety data will be available at time of presentation. In the LTE, there were 3 SAEs of infection (osteomyelitis, intervertebral discitis and cellulitis) and 3 pts discontinued due to infection (hepatitis a, Epstein-Barr virus, intervertebral discitis). No malignancies or deaths were reported, and no autoimmune events were reported as serious or led to aBA discontinuation during the LTE. AEs, SAEs and aEs of special interest occurred with a similar frequency regardless of concomitant MTX or prior TNF inhibitor (TNFi) use. The proportion of pts with anti-ABA antibodies during the cumulative aBA period was higher during the post-treatment period (≥22 days after last dose; 37.1% [91/245]) than in the on-treatment period (first treatment dose date to ≤21 days after last dose; 7.1% [28/392]). No apparent relationship between anti-ABA antibodies and efficacy in the on-treatment period or aEs suggestive of systemic immune reactions was seen.
Conclusion
Abatacept was well tolerated up to 2 years with no new safety signals during the LTE in this Phase III study in PsA. There was no impact of concomitant MTX use or prior TNFi exposure on the safety profile of abatacept. The occurrence of anti-abatacept antibodies had no impact on abatacept efficacy or safety.
References
[1] Mease PJ, et al. Ann Rheum Dis2017;76:1550–8.
Acknowledgement
Professional medical writing: andrea Plant, PhD, Caudex; funding: Bristol-Myers Squibb.
Disclosure of interests
Philip J Mease Grant/research support from: abbVie, amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: abbVie, amgen, BMS, Galapagos, Gilead Sciences, inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: abbVie, amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, alice B Gottlieb Grant/research support from: PI: incyte Corporation, Janssen-Ortho inc., Lilly ICOS LLC, Novartis, UCB, XBiotech, Consultant for: abbVie, Dermira, incyte Corporation, Lilly ICOS LLC, Novartis, Sun Pharmaceutical industries Ltd., avotres (unpaid), XBiotech (unpaid), Speakers bureau: abbVie, Eli Lilly and Company, Janssen Biotech; advisory board: Bristol-Myers Squibb, Celgene Corporation, Janssen Biotech, Janssen-Ortho inc., LEO Pharma, Novartis, UCB, Désirée van der Heijde Consultant for: abbVie, amgen, astellas, astraZeneca, Bristol-Myers Squibb, Boehringer ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge, Oliver FitzGerald: None declared, alyssa Johnsen Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Marleen Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Subhashis Banerjee Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Harris a ahmad Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Dafna D Gladman Grant/research support from: abbVie, amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: abbVie, amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB
Abstract Psoriasis is characterized by activation of T cells with a type 1 cytokine profile. IL-12 and IL-23 produced by APCs are essential for inducing Th1 effector cells. Promising clinical results of administration of an Ab specific for the p40 subunit of IL-12 and IL-23 (anti-IL-12p40) have been reported recently. This study evaluated histological changes and mRNA expression of relevant cytokines and chemokines in psoriatic skin lesions following a single administration of anti-IL-12p40, using immunohistochemistry and real-time RT-PCR. Expression levels of type 1 cytokine (IFN-γ) and chemokines (IL-8, IFN-γ-inducible protein-10, and MCP-1) were significantly reduced at 2 wk posttreatment. The rapid decrease of these expression levels preceded clinical response and histologic changes. Interestingly, the level of an anti-inflammatory cytokine, IL-10, was also significantly reduced. Significant reductions in TNF-α levels and infiltrating T cells were observed in high responders (improvement in clinical score, ≥75% at 16 wk), but not in low responders. Of importance, the levels of APC cytokines, IL-12p40 and IL-23p19, were significantly decreased in both responder populations, with larger decreases in high responders. In addition, baseline levels of TNF-α significantly correlated with the clinical improvement at 16 wk, suggesting that these levels may predict therapeutic responsiveness to anti-IL-12p40. Thus, in a human Th1-mediated disease, blockade of APC cytokines by anti-IL-12p40 down-regulates expression of type 1 cytokines and chemokines that are downstream of IL-12/IL-23, and also IL-12/IL-23 themselves, with a pattern indicative of coordinated deactivation of APCs and Th1 cells.
What is known about this subject in regard to women and their families? The University of Gondar in Gondar, Ethiopia, is part of a nationwide movement in Ethiopia to promote gender-equitable educational systems. As a result of this initiative, female residents comprise two-thirds of the current resident cohort at the Department of Dermatovenereology at the University of Gondar. High caseload and lack of resources are cited by this cohort as barriers to pursuing research during dermatology residency at the University of Gondar. What is new from this article as messages for women and their families? Brief, targeted interventions administered by partner programs with greater research resources are effective in increasing residents' level of interest and confidence in pursuing dermatology research during residency. Female dermatology residents at the University of Gondar and in other resource-limited training centers may benefit from continued efforts to incorporate targeted interventions and other systemic changes driven by global collaboration. Dear Editors, Introduction Dermatology programs in resource-limited settings manage high patient volumes.1 Trainees have extensive clinical responsibilities, which may preclude engaging in research. Programs in such settings may lack the infrastructure to provide adequate support. At the Department of Dermatovenereology at the University of Gondar in Ethiopia, residents anecdotally report a high caseload and lack of resources, including time, to pursue research. Members of Emory and Mount Sinai Dermatology designed and delivered a 30-minute presentation about research design and methods. Residents were surveyed pre- and postintervention about their attitudes toward pursuing dermatology research during residency. Methods This study (#23-00286) was deemed exempt from human research by the Mount Sinai Health Institutional Review Board. A presentation was prepared and delivered in person on February 23, 2023, by dermatology faculty and trainees at Emory and Mount Sinai Dermatology to address incorporating research during residency. Strategies were developed assuming a context of limited resources. The process of conducting literature reviews, meta-analyses, Delphi projects, survey studies, and original studies was discussed. A survey instrument was created to assess levels of interest and preparedness to pursue research among dermatology residents at the University of Gondar. The survey was administered pre- and postintervention on February 23, 2023, using ad hoc 0–10 visual analogue scales. Postintervention surveys also assessed satisfaction levels regarding the presentation. No personally identifiable information was collected. Mean values were compared using independent sample t tests. Statistical analysis was performed February 23–March 10, 2023, using Stata IC 15.0, with P < .05 in 2-sided tests considered significant. Results Residents (n = 12) in attendance completed pre- and postintervention surveys (response rate 100%). Postintervention, participants reported higher mean levels of interest (9.33 [1.23] vs 6.67 [1.97]) (P = .0007) and confidence (6.83 [1.80] vs 4.33 [2.53]) (P = .01) in performing research during residency (Fig. 1). Furthermore, participants perceived greater importance of global health collaboration for future research (10.00 [0.00] vs 7.29 [2.27]) (P = 0.004). No significant change was noted in mean scores for likelihood of undertaking ≥1 research project or for self-perceived ability to balance clinical responsibilities with research during residency. The content and length of the intervention were found to be appropriate (8.83 [1.95]) and easy to follow (9.42 [1.16]).Fig. 1.: Residents at the Department of Dermatovenereology, the University of Gondar, were surveyed pre- and postintervention to assess attitudes toward dermatology research. Mean levels of interest, confidence, and inclination for global health collaboration are indicated in the figure. All values are statistically significant as defined in the results.Discussion Limitations include single-center data collection with small sample size. This study provided insight into barriers to resident research in resource-limited settings. The intervention was rated favorably and generated interest and confidence among residents to pursue dermatology research during residency. Additionally, interest in global health collaboration increased. The results indicate that brief, targeted interventions may be effective and should be further assessed in larger cohorts and over longer time intervals. This intervention may be administered virtually, as seen with prior educational tools in global dermatology settings.2,3 The low likelihood of undertaking ≥1 project and balancing clinical responsibilities with research should be addressed in future studies. Incorporating such interventions may not be sufficient to support a research program. A comprehensive effort, including collaboration with faculty in partner programs, will be required for sustainable change. Global collaboration, particularly for research, may provide substantial value to the field of dermatology.4 Global communities should adequately represent skin of color.5 Collaboration may thereby further our understanding of dermatological disease in skin of color and instill cultural humility and competency. Conflicts of interest None. Funding None. Study approval N/A Author contributions RRR: Participated in research design, participated in the writing of the manuscript, participated in the performance of the research, contributed new reagents or analytic tools, and participated in data analysis. HAP: Participated in the writing of the manuscript, contributed new reagents or analytic tools, and participated in data analysis. JYS: Participated in the writing of the manuscript and participated in data analysis. ABG: Participated in research design and participated in data analysis. LDK: Participated in the writing of the manuscript and participated in data analysis. BKS: Participated in research design, participated in the writing of the manuscript, participated in the performance of the research, contributed new reagents or analytic tools, and participated in data analysis.
