Many options exist for the treatment of rosacea, including topical and systemic therapies, laser ... more Many options exist for the treatment of rosacea, including topical and systemic therapies, laser and light-based therapies, and surgical procedures. A classification system for rosacea identifies 4 subtypes (i.e., erythematotelangiectatic, papulopustular, phymatous, and ocular), which may help guide therapeutic decision-making. The goals of therapy include reduction of papules, pustules, erythema, physical discomfort, and an improvement in quality of life. Standard topical treatment agents include metronidazole, azelaic acid, and sodium sulfacetamide-sulfur. Second line therapies include benzoyl peroxide, clindamycin, calcineurin inhibitors, and permethrin.
Recent data have demonstrated an increasingly strong link between chronic inflammatory conditions... more Recent data have demonstrated an increasingly strong link between chronic inflammatory conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA)/psoriasis, ankylosing spondylitis (AS), and vascular events. In addition, atherosclerosis is no longer thought to be a passive disease of lipid sequestration in arteries, but rather an active inflammatory process that appears to share inflammatory and immune pathways with other chronic inflammatory conditions. This article outlines some relevant data regarding the association of chronic inflammatory disease with atherosclerosis and cardiovascular (CV) outcomes.
Phosphodiesterase 4 (PDE4) is a key enzyme in the regulation of immune responses of inflammatory... more Phosphodiesterase 4 (PDE4) is a key enzyme in the regulation of immune responses of inflammatory diseases through degradation of the second messenger, cyclic adenosine 3’,5’-monophosphate (cAMP). Apremilast, a selective PDE4 inhibitor, has been shown to reduce the production of pro-inflammatory cytokines by increasing intracellular levels of cAMP and promoting the production of anti-inflammatory cytokines. The efficacy and safety of apremilast in the treatment of psoriasis and psoriatic arthritis has been demonstrated in phase 2 and 3 studies and will be reviewed here. Across all studies, treatment was generally well-tolerated with some mild gastrointestinal complaints that occurred early and resolved over time, resulting in few drop-outs. Meaningful changes in dactylitis and enthesitis were also observed. Routine monitoring is not required given the absence of drug associated physiologic, biochemical, and haematological changes. Apremilast proves to be a new promising systemic therapy for treating psoriatic disease.
Acting on keratinocytes to produce antimicrobial peptides and chemokines, which in turn attract n... more Acting on keratinocytes to produce antimicrobial peptides and chemokines, which in turn attract neutrophils and other inflammatory cells, interleukin-17 (IL-17) is believed to be a potent driver of plaque psoriasis. Its proinflammatory characteristics make IL-17 an attractive therapeutic target for addressing immune dysregulation. This review examines the role of IL-17 in the pathogenesis of plaque psoriasis and the potential implications of its inhibition. The efficacy and safety results from Phase 2 and 3 trials with monoclonal antibodies targeting IL-17RA (brodalumab), a
Psoriasis is a chronic condition which requires ongoing management with therapies that have demon... more Psoriasis is a chronic condition which requires ongoing management with therapies that have demonstrated favorable safety and efficacy profiles in long-term use. While biologics changed the way psoriasis is treated by providing effective targeted therapy, they are not without limitations. However, small molecules are emerging therapeutic options for the treatment of psoriasis. Several oral and topical small molecules, spanning different therapeutic classes, are proving to be promising treatment options in psoriasis. While studies to date have yielded positive results, further investigation of these agents are warranted for both safety and efficacy.
Increasingly, quality of life data are being captured along with other measures to evaluate succ... more Increasingly, quality of life data are being captured along with other measures to evaluate success in the treatment of numerous disease states. This is no less true in hidradenitis suppurativa (HS), an inflammatory condition that features multiple symptoms, including abscesses that can develop in multiple sites on the body, often in sensitive areas, that can be painful, can rupture, and can produce malodorous pus. The collection of baseline data with respect to the personal impact of HS is a necessary first step to determine if various interventions enhance the quality of life for patients with HS. While no particular tool provides sufficient insight about the psychosocial impairment that HS promotes, myriad instruments that have been used to measure the quality of life of HS patients have consistently shown that the disease has a substantial adverse impact on the physical, social, and emotional well-being of patients.
Phosphodiesterase (PDE) 4 participates in regulating the inflammatory response by degrading cycli... more Phosphodiesterase (PDE) 4 participates in regulating the inflammatory response by degrading cyclic adenosine 30 ,50 -monophosphate (cAMP), a key second messenger. Inhibition of PDE4 increases the intracellular cAMP level, which in turn results in a reduction in inflammatory mediators and an increase in anti-inflamma- tory mediators. Immune-modulating effects of PDE4 inhibitors have been investigated in a number of inflam- matory conditions, such as asthma, atopic dermatitis, chronic obstructive pulmonary disease, Behc ̧et’s disease, psoriasis, and psoriatic arthritis. Apremilast, a selective PDE4 inhibitor, has been shown to block the production of pro-inflammatory cytokines (interferon-c, tumor necrosis factor-a, interleukin [IL]-12, IL-17, and IL-23), which are the key players in the pathogenesis of psoriasis. Increased intracellular cAMP levels result in a range of anti-inflammatory effects on numerous cell lines. A decrease in pro- inflammatory activity has been shown to result in a reduced psoriasiform response in preclinical in vivo models of psoriasis, and reduction of biologic activity in a pilot study in humans. The efficacy and safety of apremilast in the treatment of psoriasis have been demonstrated in phase II and III clinical trials. Apremilast demonstrated efficacy in reducing the severity of moderate to severe plaque psoriasis. Treatment with apremilast was well tolerated, with generally mild gastrointestinal complaints, which occurred early in the course of the treatment and resolved over time, and there was no requirement for laboratory test monitor- ing. These results make apremilast an attractive therapeutic option for plaque psoriasis.
Background Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associat... more Background Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoria- sis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (288%), PASI 50 (555%) and static Physician’s Global Assessment score of 0 or 1 (204%) vs. placebo (58%, 197%, 44%, respec- tively; P < 0001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed sig- nificant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks.
Plaque psoriasis has a relatively high prevalence in adolescence, resulting in a significant impa... more Plaque psoriasis has a relatively high prevalence in adolescence, resulting in a significant impact on quality of life, including social interactions. The primary objective was to assess the safety of once-daily application of fixed-combination calcipotriol plus betamethasone dipropionate gel in adolescent scalp psoriasis. Assessment of efficacy was a secondary objective. This phase II, multicentre, single-arm, open-label, 8-week trial included patients aged 12-17 years with moderate-to-very severe scalp psoriasis according to Investigator's Global Assessment (IGA) (≥ 10% of the scalp area affected). Seventy-eight patients received treatment. Twenty-seven patients (35%) reported a total of 64 adverse events (AEs); most were mild (33/64) or moderate (22/64) in severity and there were no serious AEs. No cases of hypercalcaemia were reported, and the mean changes from baseline to end of treatment in albumin-corrected serum calcium (0·00 mmol L(-1)), 24-h urinary calcium excretion (...
Many options exist for the treatment of rosacea, including topical and systemic therapies, laser ... more Many options exist for the treatment of rosacea, including topical and systemic therapies, laser and light-based therapies, and surgical procedures. A classification system for rosacea identifies 4 subtypes (i.e., erythematotelangiectatic, papulopustular, phymatous, and ocular), which may help guide therapeutic decision-making. The goals of therapy include reduction of papules, pustules, erythema, physical discomfort, and an improvement in quality of life. Standard topical treatment agents include metronidazole, azelaic acid, and sodium sulfacetamide-sulfur. Second line therapies include benzoyl peroxide, clindamycin, calcineurin inhibitors, and permethrin.
Recent data have demonstrated an increasingly strong link between chronic inflammatory conditions... more Recent data have demonstrated an increasingly strong link between chronic inflammatory conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA)/psoriasis, ankylosing spondylitis (AS), and vascular events. In addition, atherosclerosis is no longer thought to be a passive disease of lipid sequestration in arteries, but rather an active inflammatory process that appears to share inflammatory and immune pathways with other chronic inflammatory conditions. This article outlines some relevant data regarding the association of chronic inflammatory disease with atherosclerosis and cardiovascular (CV) outcomes.
Phosphodiesterase 4 (PDE4) is a key enzyme in the regulation of immune responses of inflammatory... more Phosphodiesterase 4 (PDE4) is a key enzyme in the regulation of immune responses of inflammatory diseases through degradation of the second messenger, cyclic adenosine 3’,5’-monophosphate (cAMP). Apremilast, a selective PDE4 inhibitor, has been shown to reduce the production of pro-inflammatory cytokines by increasing intracellular levels of cAMP and promoting the production of anti-inflammatory cytokines. The efficacy and safety of apremilast in the treatment of psoriasis and psoriatic arthritis has been demonstrated in phase 2 and 3 studies and will be reviewed here. Across all studies, treatment was generally well-tolerated with some mild gastrointestinal complaints that occurred early and resolved over time, resulting in few drop-outs. Meaningful changes in dactylitis and enthesitis were also observed. Routine monitoring is not required given the absence of drug associated physiologic, biochemical, and haematological changes. Apremilast proves to be a new promising systemic therapy for treating psoriatic disease.
Acting on keratinocytes to produce antimicrobial peptides and chemokines, which in turn attract n... more Acting on keratinocytes to produce antimicrobial peptides and chemokines, which in turn attract neutrophils and other inflammatory cells, interleukin-17 (IL-17) is believed to be a potent driver of plaque psoriasis. Its proinflammatory characteristics make IL-17 an attractive therapeutic target for addressing immune dysregulation. This review examines the role of IL-17 in the pathogenesis of plaque psoriasis and the potential implications of its inhibition. The efficacy and safety results from Phase 2 and 3 trials with monoclonal antibodies targeting IL-17RA (brodalumab), a
Psoriasis is a chronic condition which requires ongoing management with therapies that have demon... more Psoriasis is a chronic condition which requires ongoing management with therapies that have demonstrated favorable safety and efficacy profiles in long-term use. While biologics changed the way psoriasis is treated by providing effective targeted therapy, they are not without limitations. However, small molecules are emerging therapeutic options for the treatment of psoriasis. Several oral and topical small molecules, spanning different therapeutic classes, are proving to be promising treatment options in psoriasis. While studies to date have yielded positive results, further investigation of these agents are warranted for both safety and efficacy.
Increasingly, quality of life data are being captured along with other measures to evaluate succ... more Increasingly, quality of life data are being captured along with other measures to evaluate success in the treatment of numerous disease states. This is no less true in hidradenitis suppurativa (HS), an inflammatory condition that features multiple symptoms, including abscesses that can develop in multiple sites on the body, often in sensitive areas, that can be painful, can rupture, and can produce malodorous pus. The collection of baseline data with respect to the personal impact of HS is a necessary first step to determine if various interventions enhance the quality of life for patients with HS. While no particular tool provides sufficient insight about the psychosocial impairment that HS promotes, myriad instruments that have been used to measure the quality of life of HS patients have consistently shown that the disease has a substantial adverse impact on the physical, social, and emotional well-being of patients.
Phosphodiesterase (PDE) 4 participates in regulating the inflammatory response by degrading cycli... more Phosphodiesterase (PDE) 4 participates in regulating the inflammatory response by degrading cyclic adenosine 30 ,50 -monophosphate (cAMP), a key second messenger. Inhibition of PDE4 increases the intracellular cAMP level, which in turn results in a reduction in inflammatory mediators and an increase in anti-inflamma- tory mediators. Immune-modulating effects of PDE4 inhibitors have been investigated in a number of inflam- matory conditions, such as asthma, atopic dermatitis, chronic obstructive pulmonary disease, Behc ̧et’s disease, psoriasis, and psoriatic arthritis. Apremilast, a selective PDE4 inhibitor, has been shown to block the production of pro-inflammatory cytokines (interferon-c, tumor necrosis factor-a, interleukin [IL]-12, IL-17, and IL-23), which are the key players in the pathogenesis of psoriasis. Increased intracellular cAMP levels result in a range of anti-inflammatory effects on numerous cell lines. A decrease in pro- inflammatory activity has been shown to result in a reduced psoriasiform response in preclinical in vivo models of psoriasis, and reduction of biologic activity in a pilot study in humans. The efficacy and safety of apremilast in the treatment of psoriasis have been demonstrated in phase II and III clinical trials. Apremilast demonstrated efficacy in reducing the severity of moderate to severe plaque psoriasis. Treatment with apremilast was well tolerated, with generally mild gastrointestinal complaints, which occurred early in the course of the treatment and resolved over time, and there was no requirement for laboratory test monitor- ing. These results make apremilast an attractive therapeutic option for plaque psoriasis.
Background Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associat... more Background Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoria- sis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (288%), PASI 50 (555%) and static Physician’s Global Assessment score of 0 or 1 (204%) vs. placebo (58%, 197%, 44%, respec- tively; P < 0001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed sig- nificant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks.
Plaque psoriasis has a relatively high prevalence in adolescence, resulting in a significant impa... more Plaque psoriasis has a relatively high prevalence in adolescence, resulting in a significant impact on quality of life, including social interactions. The primary objective was to assess the safety of once-daily application of fixed-combination calcipotriol plus betamethasone dipropionate gel in adolescent scalp psoriasis. Assessment of efficacy was a secondary objective. This phase II, multicentre, single-arm, open-label, 8-week trial included patients aged 12-17 years with moderate-to-very severe scalp psoriasis according to Investigator's Global Assessment (IGA) (≥ 10% of the scalp area affected). Seventy-eight patients received treatment. Twenty-seven patients (35%) reported a total of 64 adverse events (AEs); most were mild (33/64) or moderate (22/64) in severity and there were no serious AEs. No cases of hypercalcaemia were reported, and the mean changes from baseline to end of treatment in albumin-corrected serum calcium (0·00 mmol L(-1)), 24-h urinary calcium excretion (...
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Papers by M. Gooderham
Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis.
Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoria- sis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast.
Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (288%), PASI 50 (555%) and static Physician’s Global Assessment score of 0 or 1 (204%) vs. placebo (58%, 197%, 44%, respec- tively; P < 0001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed sig- nificant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection.
Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks.
Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis.
Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoria- sis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast.
Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (288%), PASI 50 (555%) and static Physician’s Global Assessment score of 0 or 1 (204%) vs. placebo (58%, 197%, 44%, respec- tively; P < 0001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed sig- nificant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection.
Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks.