Gene Therapy for Parkinson’s Disease

Gene therapy is a promising future tool for treatment of Parkinson’s disease (PD) and several different strategies are currently being evaluated. Although many of these strategies have shown promising results in animal models of PD and parkinsonian patients, some have been less effective and caused adverse side effects. A vector system with high specificity and appropriate expression level of the transgene is needed to make gene therapy for PD as safe and beneficial as possible. The vector should also be relevant for the disease. Here, we present a method to design promoters relevant for PD, using microarray data from patients, and validation of these in vivo. The method also includes fine-tuning of promoter candidates by adding miRNA target sites to increase cell specificity

Functional Neuroprotection and Efficient Regulation of GDNF Using Destabilizing Domains in a Rodent Model of Parkinson's Disease

Glial cell line derived neurotrophic factor (GDNF) has great potential to treat Parkinson's disease (PD). However, constitutive expression of GDNF can over time lead to side effects. Therefore, it would be useful to regulate GDNF expression. Recently, a new gene inducible system using destabilizing domains (DD) from E. coil dihydrofolate reductase (DHFR) has been developed and characterized. The advantage of this novel DD is that it is regulated by trimethoprim (TMP), a well-characterized drug that crosses the blood brain barrier and can therefore be used to regulate gene expression in the brain. We have adapted this system to regulate expression of GDNF. A C-terminal fusion of GDNF and a DD with an additional furin cleavage site was able to be efficiently regulated in vitro, properly processed and was able to bind to canonical GDNF receptors, inducing a signaling cascade response in target cells. In vivo characterization of the protein showed that it could be efficiently induced by TMP and it was only functional when gene expression was turned on. Further characterization in a rodent model of PD showed that the regulated GDNF protected neurons, improved motor behavior of animals and was efficiently regulated in a pathological setting

Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9.

Functional studies of resident microglia require molecular tools for their genetic manipulation. Here we show that microRNA-9-regulated lentiviral vectors can be used for the targeted genetic modification of resident microglia in the rodent brain. Using transgenic reporter mice, we demonstrate that murine microglia lack microRNA-9 activity, whereas most other cells in the brain express microRNA-9. Injection of microRNA-9-regulated vectors into the adult rat brain induces transgene expression specifically in cells with morphological features typical of ramified microglia. The majority of transgene-expressing cells colabels with the microglia marker Iba1. We use this approach to visualize and isolate activated resident microglia without affecting circulating and infiltrating monocytes or macrophages in an excitotoxic lesion model in rat striatum. The microRNA-9-regulated vectors described here are a straightforward and powerful tool that facilitates functional studies of resident microglia

Latent tuberculosis infection in patients with chronic plaque psoriasis: Evidence from the Italian Psocare Registry

Background The nationwide prevalence of latent tuberculosis infection (LTBI) in Italian patients with psoriasis has never been investigated.Objectives To estimate the nationwide prevalence of LTBI in Italian patients with psoriasis who are candidates for systemic treatment.Methods Data were obtained from the Psocare Registry on those patients (n = 4946) with age > 18 years, systemic treatment at entry specified and tuberculin skin test (TST) performed according to the Mantoux method. LTBI diagnosis was based on a positive TST result in the absence of any clinical, radiological or microbiological evidence of active tuberculosis.Results Latent tuberculosis infection was diagnosed in 8.3% of patients with psoriasis (409 of 4946). The prevalence of LTBI was lower in patients on biologics than in those on conventional systemic treatments, ranging from 4.3% (19 of 444) of patients on adalimumab to 31% (eight of 26) of those on psoralenultraviolet A (P < 0.05). Independent factors associated with LTBI were male sex [odds ratio (OR) 1.30, 95% confidence interval (CI) 1.04-1.62; P = 0.02], age over 55 years (OR 2.93, 95% CI 2.18-3.93; P < 0.001) and being entered into a conventional treatment (OR 3.83, 95% CI 3.10-4.74; P < 0.001). Positive history of tuberculosis was seen in 1% of patients (n = 49).Conclusions The nationwide prevalence of LTBI in Italian patients with psoriasis candidate to systemic treatment is high, and screening is recommended prior to biological treatment

Metabolic abnormalities associated with initiation of systemic treatment for psoriasis: evidence from the Italian Psocare Registry.

Objective To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to 16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees. Design Prospective cohort study. Setting Italian public referral centres for psoriasis treatment. Patients First-time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks. Main outcome measure Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinically meaningful increase in serum levels (week 16) of total and low-density lipoprotein cholesterol, triglycerides, aspartate amino transferase, alanine amino transferase and creatinine, as well as week-16 cumulative incidences of new diagnoses of diabetes mellitus and arterial hypertension. Results Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin or cyclosporine. Mean triglyceride levels also increased in efalizumab- and etanercept-treated patients. Mean transaminase values increased in methotrexate-treated patients, and mean aspartate amino transferase levels increased in infliximab-treated patients. The average serum creatinine value increased in cyclosporine-treated patients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34) and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated with risk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanine amino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension and diabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88). Conclusion Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed

Pruritus characteristics in a large Italian cohort of psoriatic patients

none368nononeDamiani, G.; Cazzaniga, S.; Conic, R.R.Z.; Naldi, L.; Griseta, V.; Miracapillo, A.; Azzini, M.; Mocci, L.; Michelini, M.; Offidani, A.; Bernardini, L.; Campanati, A.; Ricotti, G.; Giacchetti, A.; Norat, M.; Gualco, F.; Castelli, A.; Cuccia, A.; Diana, A.; Roncarolo, G.; Belli, M.A.; Baldassarre, M.A.; Santoro, G.; Vena, G.A.; Lo Console, F.; Filotico, R.; Mastrandrea, V.; Brunetti, B.; Musumeci, F.; Carrabba, E.; Dal Mas, P.; Annicchiarico, F.; Benvegn_u, B.; Spaziani, G.; Cusano, F.; Saletta Iannazzone, S.; Galluccio, A.; Pezza, M.; Marchesi, L.; Imberti, G.; Reseghetti, A.; Barbera, C.; Reggiani, M.; Lanzoni, A.; Patrizi, A.; Bardazzi, F.; Antonucci, A.; De Tommaso, S.; Wallnofer, W.; Ingannamorte, F.; Calzavara-Pinton, P.; Iannazzi, S.; Zane, C.; Capezzera, R.; Bassisi, S.; Rossi, M.T.; Altamura, V.; Vigl, W.; Nobile, C.; Aste, N.; Murgia, S.; Mugheddu, C.; Scuderi, G.; Baglieri, F.; Di Dio, C.; Cilioni Grilli, E.; Mastronardi, C.; Agnusdei, C.P.; Antrilli, A.; Aulisa, L.; Raimondo, U.; Scotto di Luzio, G.; Battarra, V.C.; Farro, P.; Plaitano, R.; Micali, G.; Musumeci, M.L.; Massimino, D.; Li Calzi, M.; La Greca, S.; Pettinato, M.; Sapienza, G.; Valenti, G.; De Giacomo, P.F.; Amico, .; Arcangeli, F.; Brunelli, D.; Ghetti, E.; Tulli, A.; Assi, G.; Amerio, P.; Laria, G.; Prestinari, F.; Spadafora, S.; Coppola, M.; Caresana, G.; Pezzarossa, E.; Felisi, C.; Donato, L.; Bertero, M.; Musso, L.; Pa lazzini, S.; Bruscino, P.; Agozzino, U.C.; Ottaviani, M.; Simoncini, C.; Virgili, A.; Osti, F.; Fabbri, P.; Volpi, W.; Caproni, M.; Lotti, T.; Prignano, F.; Buggiani, G.; Troiano, M.; Fenizi, G.; Altobella, A.; Amoruso, A.; Condello, M.; Goffredo, A.; Righini, M.G.; Alessandrini, F.; Satolli, F.; Zampetti, M.; Bertani, E.; Fossati, S.; Parodi, A.; Burlando, M.; Fiorucci, C.; Nigro, A.; Ghigliotti, G.; Massone, L.; Moise, G.M.; Serrai, M.; Cannata, G.; Campagnoli, A.M.; Daly, M.; Leporati, C.; Peila, R.; Filosa, G.; Bugatti, L.; Nicolini, M.; Nazzari, G.; Cestari, R.; Anastasio, F.; Larussa, F.M.; Pollice, N.; De Francesco, F.; Mazzocchetti, G.; Peris, K.; Fargnoli, M.C.; Di Cesare, A.; De Angelis, L.; Flati, G.; Biamonte, A.S.; Quarta, G.; Congedo, M.; Carcaterra, A.; Strippoli, D.; Fideli, D.; Marsili, F.; Celli, M.; Ceccarini, M.; Bachini, L.; D'Oria, M.; Schirripa, V.; De Filippi, C.; Martini, P.; Lapucci, E.; Mazzatenta, C.; Ghilardi, A.; Simonacci, M.; Bettacchi, A.; Gasco, R.; Zanca, A.; Battistini, S.; Dattola, S.; Vernaci, R.; Postorino, F.; Zampieri, P.F.; Padovan, C.; Gonz_alez Intchaurraga, M.A.; Ladurner, J.; Guarneri, B.; Cannav_o, S.; Manfr_e, C.; Borgia, F.; Puglisi Guerra, A.; Cattaneo, A.; Carrera, C.; Fracchiolla, C.; Mozzanica, N.; Prezzemolo, L.; Menni, S.; Lodi, A.; Martino, P.; Monti, M.; Mancini, L.; Sacrini, F.; Altomare, G.F.; Taglioni, M.; Lovati, C.; Mercuri, S.R.; Schiesari, G.; Giannetti, A.; Conti, A.; Lasagni, C.; Greco, M.; Ronsini, G.; Schianchi, S.; Fiorentini, C.; Niglietta, S.; Maglietta, R.; Padalino, C.; Crippa, D.; Pini, M.; Rossi, E.; Tosi, D.; Armas, M.; Ruocco, V.; Ayala, F.; Balato, N.; Gaudiello, F.; Cimmino, G.F.; Monfrecola, G.; Gallo, L.; Argenziano, G.; Fulgione, E.; Berruti, G.; Ceparano, S.; De Michele, I.; Giorgiano, D.; Leigheb, G.; Deledda, S.; Peserico, A.; Alaibac, M.; Piaserico, S.; Schiesari, L.; Dan, G.; Mattei, I.; Oro, E.; Aric_o, M.; Bongiorno, M.R.; Angileri, R.; Amato, S.; Todaro, F.; Milioto, M.; Bellastro, R.; Di Nuzzo, S.; De Panfilis, G.; Zanni, M.; Borroni, G.; Cananzi, R.; Brazzelli, V.; Lisi, P.; Stingeni, L.; Hansel, K.; Pierfelice, V.; Donelli, S.; Rastelli, D.; Gasperini, M.; Barachini, P.; Cecchi, R.; Bartoli, L.; Pavesi, M.; De Paola, S.; Corradin, M.T.; Ricciuti, F.; Piccirillo, A.; Viola, L.; Tataranni, M.; Mautone, M.G.; Lo Scocco, G.; Niccoli, M.C.; Brunasso Vernetti, A.M.G.; Gaddoni, G.; Resta, F.; Casadio, M.C.; Arcidiaco, M.C.; Luvar_a, M.C.; Albertini, G.; Di Lernia, V.; Guareschi, E.; Catrani, S.; Morri, M.; Amerio, P.; De Simone, C.; D'Agostino, M.; Agostino, I.; Calvieri, S.; Cantoresi, F.; Richetta, A.; Sorgi, P.; Carnevale, C.; Nicolucci, F.; Berardesca, E.; Ardig_o, M.; De Felice, C.; Gubinelli, E.; Talamonti, M.; Camplone, G.; Cruciani, G.; Riccardi, F.; Barbati, R.; Zumiani, G.; Pagani, W.; Malagoli, P.G.; Pellicano, R.; Donadio, D.; Di Vito, C.; Cottoni, F.; Montesu, M.A.; Pirodda, C.; Addis, G.; Marongiu, P.; Farris, A.; Cacciapuoti, M.; Verrini, A.; Desirello, G.; Gnone, M.; Fimiani, M.; Pellegrino, M.; Castelli, G.; Zappal_a, L.; Sesana, G.; Ingordo, V.; Vozza, E.; Di Giuseppe, D.; Fasciocco, D.; Nespoli, P.; Papini, M.; Cicoletti, M.; Bernengo, M.G.; Ortoncelli, M.; Bonvicino, A.; Capella, G.; Doveil, G.C.; Forte, M.; Peroni, A.; Salomone, B.; Savoia, P.; Pippione, M.; Zichichi, L.; Frazzitta, M.; De Luca, G.; Zumiani, G.; Tasin, L.; Simonetto, D.; Ros, S.; Trevisan, G.; Patamia, M.; Miertusova, S.; Patrone, P.; Frattasio, A.; Piccirillo, F.; La Spina, S.; Di Gaetano, L.; Marzocchi, V.; Motolese, A.; Venturi, C.; Gai, F.; Pasquinucci, S.; Bellazzi, R.M.; Silvestri, T.; Girolomoni, G.; Gisondi, P.; Veller Fornasa, C.; Trevisan, G.P.Damiani, Giulia; Cazzaniga, S.; Conic, R. R. Z.; Naldi, L.; Griseta, V.; Miracapillo, A.; Azzini, M.; Mocci, L.; Michelini, M.; Offidani, A.; Bernardini, L.; Campanati, A.; Ricotti, G.; Giacchetti, A.; Norat, M.; Gualco, F.; Castelli, A.; Cuccia, A.; Diana, A.; Roncarolo, G.; Belli, M. A.; Baldassarre, M. A.; Santoro, G.; Vena, G. A.; Lo Console, F.; Filotico, R.; Mastrandrea, V.; Brunetti, B.; Musumeci, F.; Carrabba, E.; Dal Mas, P.; Annicchiarico, F.; Benvegn_u, B.; Spaziani, G.; Cusano, F.; Saletta Iannazzone, S.; Galluccio, A.; Pezza, M.; Marchesi, L.; Imberti, G.; Reseghetti, A.; Barbera, C.; Reggiani, M.; Lanzoni, A.; Patrizi, A.; Bardazzi, F.; Antonucci, DIEGO ADRIAN; De Tommaso, S.; Wallnofer, W.; Ingannamorte, F.; Calzavara-Pinton, P.; Iannazzi, S.; Zane, C.; Capezzera, R.; Bassisi, S.; Rossi, M. T.; Altamura, V.; Vigl, W.; Nobile, C.; Aste, N.; Murgia, S.; Mugheddu, C.; Scuderi, Gianluca; Baglieri, F.; Di Dio, C.; Cilioni Grilli, E.; Mastronardi, C.; Agnusdei, C. P.; Antrilli, A.; Aulisa, L.; Raimondo, U.; Scotto di Luzio, G.; Battarra, V. C.; Farro, P.; Plaitano, R.; Micali, G.; Musumeci, M. L.; Massimino, D.; LI CALZI, Marco; La Greca, S.; Pettinato, M.; Sapienza, G.; Valenti, G.; De Giacomo, P. F.; Amico, .; Arcangeli, F.; Brunelli, Donatella; Ghetti, E.; Tulli, A.; Assi, G.; Amerio, P.; Laria, G.; Prestinari, F.; Spadafora, S.; Coppola, M.; Caresana, G.; Pezzarossa, E.; Felisi, C.; DI DONATO, Luca; Bertero, M.; Musso, L.; Pa lazzini, S.; Bruscino, P.; Agozzino, U. C.; Ottaviani, M.; Simoncini, Claudia; Virgili, A.; Osti, F.; Fabbri, Paolo; Volpi, W.; Caproni, M.; Lotti, T.; Prignano, F.; Buggiani, G.; Troiano, M.; Fenizi, G.; Altobella, A.; Amoruso, A.; Condello, M.; Goffredo, A.; Righini, M. G.; Alessandrini, F.; Satolli, F.; Zampetti, M.; Bertani, E.; Fossati, S.; Parodi, A.; Burlando, M.; Fiorucci, C.; Nigro, A.; Ghigliotti, G.; Massone, L.; Moise, G. M.; Serrai, M.; Cannata, G.; Campagnoli, A. M.; Daly, M.; Leporati, C.; Peila, R.; Filosa, G.; Bugatti, L.; Nicolini, M.; Nazzari, G.; Cestari, R.; Anastasio, F.; Larussa, F. M.; Pollice, N.; De Francesco, F.; Mazzocchetti, Gabriele; Peris, K.; Fargnoli, M. C.; Di Cesare, A.; DE ANGELIS, Luca; Flati, G.; Biamonte, A. S.; Quarta, G.; Congedo, M.; Carcaterra, A.; Strippoli, D.; Fideli, D.; Marsili, F.; Celli, Maria; Ceccarini, M.; Bachini, L.; D'Oria, M.; Schirripa, V.; De Filippi, C.; Martini, P.; Lapucci, E.; Mazzatenta, C.; Ghilardi, A.; Simonacci, M.; Bettacchi, A.; Gasco, R.; Zanca, A.; Battistini, S.; Dattola, S.; Vernaci, R.; Postorino, F.; Zampieri, P. F.; Padovan, C.; Gonz_alez Intchaurraga, M. A.; Ladurner, J.; Guarneri, B.; Cannav_o, S.; Manfr_e, C.; Borgia, F.; Puglisi Guerra, A.; Cattaneo, A.; Carrera, C.; Fracchiolla, C.; Mozzanica, N.; Prezzemolo, L.; Menni, S.; Lodi, A.; Martino, P.; Monti, Marina; Mancini, L.; Sacrini, F.; Altomare, G. F.; Taglioni, M.; Lovati, C.; Mercuri, S. R.; Schiesari, G.; Giannetti, Anna; Conti, A.; Lasagni, C.; Greco, M.; Ronsini, G.; Schianchi, S.; Fiorentini, C.; Niglietta, S.; Maglietta, R.; Padalino, C.; Crippa, D.; Pini, M.; Rossi, E.; Tosi, D.; Armas, M.; Ruocco, V.; Ayala, F.; Balato, N.; Gaudiello, F.; Cimmino, G. F.; Monfrecola, G.; Gallo, L.; Argenziano, G.; Fulgione, E.; Berruti, G.; Ceparano, S.; De Michele, I.; Giorgiano, D.; Leigheb, G.; Deledda, S.; Peserico, A.; Alaibac, M.; Piaserico, S.; Schiesari, L.; Dan, G.; Mattei, I.; Oro, E.; Aric_o, M.; Bongiorno, M. R.; Angileri, R.; D'Amato, Sonia; Todaro, F.; Milioto, M.; Bellastro, R.; Di Nuzzo, S.; De Panfilis, G.; Zanni, M.; Borroni, Giovanni Marco; Cananzi, R.; Brazzelli, V.; Lisi, P.; Stingeni, L.; Hansel, K.; Pierfelice, V.; Donelli, S.; Rastelli, D.; Gasperini, M.; Barachini, P.; Cecchi, R.; Bartoli, L.; Pavesi, M.; De Paola, S.; Corradin, M. T.; Ricciuti, F.; Piccirillo, A.; Viola, L.; Tataranni, M.; Mautone, M. G.; Lo Scocco, G.; Niccoli, M. C.; Brunasso Vernetti, A. M. G.; Gaddoni, G.; Resta, F.; Casadio, M. C.; Arcidiaco, M. C.; Luvar_a, M. C.; Albertini, G.; Di Lernia, V.; Guareschi, E.; Catrani, S.; Morri, M.; Amerio, P.; De Simone, C.; D'Agostino, M.; Agostino, I.; Calvieri, S.; Cantoresi, F.; Richetta, A.; Sorgi, P.; Carnevale, C.; Nicolucci, F.; Berardesca, E.; Ardig_o, M.; De Felice, C.; Gubinelli, E.; Talamonti, Marco Claudio; Camplone, G.; Cruciani, G.; Riccardi, F.; Barbati, R.; Zumiani, G.; Pagani, W.; Malagoli, P. G.; Pellicano, R.; Donadio, D.; Di Vito, C.; Cottoni, F.; Montesu, M. A.; Pirodda, C.; Addis, G.; Marongiu, P.; Farris, A.; Cacciapuoti, M.; Verrini, A.; Desirello, G.; Gnone, M.; Fimiani, M.; Pellegrino, M.; Castelli, G.; Zappal_a, L.; Sesana, G.; Ingordo, V.; Vozza, E.; Di Giuseppe, D.; Fasciocco, D.; Nespoli, P.; Papini, M.; Cicoletti, M.; Bernengo, M. G.; Ortoncelli, M.; Bonvicino, A.; Capella, G.; Doveil, G. C.; Forte, M.; Peroni, A.; Salomone, B.; Savoia, P.; Pippione, M.; Zichichi, L.; Frazzitta, M.; De Luca, G.; Zumiani, G.; Tasin, L.; Simonetto, D.; Ros, S.; Trevisan, G.; Patamia, M.; Miertusova, S.; Patrone, P.; Frattasio, A.; Piccirillo, F.; La Spina, S.; Di Gaetano, L.; Marzocchi, V.; Motolese, Alfonso; Venturi, C.; Gai, F.; Pasquinucci, S.; Bellazzi, R. M.; Silvestri, T.; Girolomoni, G.; Gisondi, P.; Veller Fornasa, C.; Trevisan, G. P

Metabolic abnormalities associated with initiation of systemic treatment for psoriasis: Evidence from the Italian Psocare Registry

Objective To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to 16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees. Design Prospective cohort study. Setting Italian public referral centres for psoriasis treatment. Patients First-time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks. Main outcome measure Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinically meaningful increase in serum levels (week 16) of total and low-density lipoprotein cholesterol, triglycerides, aspartate amino transferase, alanine amino transferase and creatinine, as well as week-16 cumulative incidences of new diagnoses of diabetes mellitus and arterial hypertension. Results Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin or cyclosporine. Mean triglyceride levels also increased in efalizumab- and etanercept-treated patients. Mean transaminase values increased in methotrexate-treated patients, and mean aspartate amino transferase levels increased in infliximab-treated patients. The average serum creatinine value increased in cyclosporine-treated patients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34) and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated with risk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanine amino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension and diabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88). Conclusion Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed. \ua9 2012 European Academy of Dermatology and Venereology

Efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis: Results from the Italian Psocare Registry

Background Some studies have shown that switching patients from one tumor necrosis factor (TNF)-alfa inhibitor to another may be beneficial when they have an inadequate response or an adverse event. Objective We sought to assess the variables predicting the efficacy of the second TNF-alfa inhibitor in patients discontinuing the first TNF-alfa inhibitor. Methods Data from all 5423 consecutive patients starting TNF-alfa inhibitor therapy for psoriasis between September 2005 and September 2010 who were included in the Italian Psocare registry were analyzed. Results In 105 patients who switched to a second TNF-alfa inhibitor who had complete follow-up data, 75% improvement in the Psoriasis Area Severity Index score (PASI 75) was reached by 29% after 16 weeks and by 45.6% after 24 weeks. Patients who switched because of secondary loss of efficacy (loss of initial PASI 75 response) or adverse events/intolerance were more likely to reach PASI 75 than those who switched as a result of primary inefficacy (PASI 75 never achieved) (hazard ratio 2.7, 95% confidence interval 1.3-5.5 vs hazard ratio 2.0, 95% confidence interval 1.0-3.9 and 1, respectively). Limitations There was a small number of patients with complete follow-up data. Conclusion PASI 75 response in patients who switched from one anti-TNF-alfa agent to another was significantly reduced in patients who showed primary inefficacy of the first anti-TNF-alfa. © 2013 by the American Academy of Dermatology, Inc