A Randomized, Double-blind, Placebo- controlled Study to Evaluate the Safety and Efficacy of Ammonium Lactate Lotion 12% and Halobetasol Propionate Ointment 0.05% in the Treatment and Maintenance of Psoriasis
Jason J. Emer, MD; Amylynne Frankel, MD; Andrew Sohn, BS; Mark Lebwohl, MD
Mount Sinai School of Medicine, Department of Dermatology, New York, New York
Disclosure: Dr. Emer, Dr. Frankel, and Mr. Sohn report no relevant conflicts of interest. Dr. Lebwohl lectures for Ranbaxy. Funding sources for this study were provided by Ranbaxy Laboratories, Inc. The data for this clinical trial have been presented in poster format at the Winter Clinical Dermatology Conference, Grand Hyatt Kauai, Hawaii; January 23–28, 2010, and the Fall Clinical Dermatology Conference, Wynn Hotel, Las Vegas, Nevada; October 16–19, 2010.
Consensus recommends a gradual reduction in the frequency or steroid potency of topical corticosteroids following clinical improvement in the treatment of psoriasis, although no established guidelines have been developed. The authors sought to evaluate a combination regimen in the treatment and maintenance of psoriasis. Patients with mild-to-moderate psoriasis were enrolled (n=55) in a randomized, double-blind, placebo-controlled study using ammonium lactate lotion and halobetasol ointment. Those with initial improvement of target plaques after two weeks of combination treatment twice daily were randomized to a maintenance phase (n=41). Patients applied ammonium lactate lotion twice daily everyday and either placebo ointment (n=20) or steroid ointment (n=21) twice daily on weekends only. Forty-one of 55 patients (74.6%) were rated as “clear” (0) or “almost clear” (1) after two weeks of combination treatment. In the maintenance phase, the probability of physician global assessment worsening at six weeks in the steroid group was only 10 percent while in the placebo group the probability rose to 75 percent (p<0.0001). The probability of physician global assessment worsening climbed to 100 percent by 14 weeks in the placebo group while only increasing to 29 percent in the steroid group (p<0.0001).
Twelve patients at study termination still had not worsened. Worsening of the physician global assessment index was more likely (HR 7.8 [2.84, 21.43]) in the placebo group than in the steroid group (p<0.0001). No cutaneous side effects, such as steroid atrophy or irritation, were noted. Combination treatment effectively cleared plaque psoriasis initially, and ammonium lactate twice daily everyday with weekend-only applications of halobetasol ointment effectively sustained the initial improvement for a significantly longer period of time when compared with placebo without demonstrating any significant side effects, such as steroid atrophy.
(J Clin Aesthet Dermatol. 2011;4(2):28–39.)
Psoriasis is a chronic inflammatory skin disorder with a prevalence of approximately 1 to 3 percent worldwide. The most common form is plaque psoriasis (psoriasis vulgaris), which accounts for the majority of cases. Psoriasis is characterized by well-circumscribed, erythematous plaques with scale that represent a response to an infiltration of inflammatory T-cells producing disease-stimulating cytokines in skin lesions. Although many treatments have success in initial clearance, the long-term maintenance of disease is disputed since no current treatment is curative. Topical therapies, including topical corticosteroids, are the most commonly used agents as the first-line treatment of psoriasis and can be used as monotherapy or in combination with other agents.[3,4] The long-term use of superpotent topical corticosteroids can have a multitude of unwanted cutaneous side effects, such as skin atrophy, telangiectasia, striae, tachyphylaxis, and allergy.[5,6]
The majority of patients with psoriasis have limited disease affecting only a small body surface area (BSA). Superpotent topical corticosteroids generally provide a quick improvement with an excellent safety profile in patients with limited disease. In the setting of more extensive or recalcitrant disease, the risk of detrimental side effects, including increased systemic absorption inhibiting the hypothalamic-pituitary-adrenal (HPA) axis, and/or local cutaneous side effects is increased with continuous monotherapy treatment and is not routinely recommended.[7,8] Patients with exceptionally indurated, coarsely scaled, chronic plaques often require treatment with the highest potency topical corticosteroids as monotherapy or frequently in combination with another agent for synergy or as a steroid-sparing option.[9-11]
Efficacy rates of topical corticosteroids vary among the different classes and within those of the same class, making the choice of a particular agent or class difficult. Of the four vehicle- or placebo-controlled trials of class I corticosteroids, efficacy rates (success defined as “clear” or “almost clear”) are varied between 58 to 92 percent, thus the specifics of the primary endpoint used in each study has an important bearing on the percentage of improvement noted.[7,12–15] One must keep in mind that a variety of factors can affect the efficacy of topical corticosteroids, such as medication vehicle, location of use, presence or absence of occlusion, patient preference, and treatment adherence. Therefore, when critically examining the results of a trial, one must consider the variety of factors that may influence the results as well as the evaluation scales used for scoring percent improvements, as this can have a profound influence on overall outcome measures.
Local cutaneous side effects occur much more frequently than systemic side effects, especially in intertriginous (axillae and groin) and thinner skin areas (face). For superpotent topical corticosteroids, the package inserts advise no more than 2 to 4 weeks of continuous use to limit adverse side effects. General consensus recommends that a gradual reduction in the frequency (“weekend” or “pulse” therapy) or potency (“step-down” therapy) of a topical corticosteroid be instituted after initial clinical improvement for long-term maintenance without subjecting the skin to corticosteroid-associated side effects. Adding a second agent (keratolytic, emollient, vitamin D analogue) may also help effectively maintain clearance and offer a corticosteroid-sparing option. A meta-analysis of 22 studies reported that clearing rates following monotherapy ranged from 2 to 85 percent versus clearance rates of 39 to 100 percent for combination therapies. Combination therapies involve using a pair of drugs concomitantly in order to optimize their effectiveness. Lower doses of an individual agent may be used with the potential for synergistic therapeutic effects of the medications in combination. The goal of these regimens is to help limit side effects or lack of medication effectiveness over time.[18,19] Clinical trials involving combination modalities (calcipotriene, tazarotene, tacrolimus, pimecrolimus, salicylic acid, anthralin, tar, nonmedicated topical moisturizers) have demonstrated increased clinical benefit when compared with corticosteroid monotherapy.[18,20,21]
Ammonium lactate lotion 12% (Lac-Hydrin®; Ranbaxy Laboratories Inc, Jacksonville, Florida) is composed of ammonium lactate (lactic acid), cetyl alcohol, glycerin, magnesium aluminum silicate, water, light mineral oil, propylene glycol, methyl and propylparabens, laureth-4, and polyoxyl 40 stearate.[22,23] When applied to the skin, it has been shown to create a stimulatory response that induces an epidermal proliferation increasing epidermal thickness and hydration and an increased number of granular layers and underlying dermal cells. Lactic acid is an alpha-hydroxy acid and may act as a humectant when applied to the skin. Currently, ammonium lactate lotion is approved for the treatment of dry, scaly skin (xerosis) and ichthyosis vulgaris to aid in the temporary relief of itching associated with these conditions. In one pivotal trial, ammonium lactate lotion was evaluated to determine whether the increase in epidermal thickness was effective in reversing or preventing the atrophic response to topical corticosteroids. The study concluded that concomitant use of ammonium lactate lotion with a potent topical corticosteroid resulted in significant sparing of atrophy in both the epidermis and dermis.
The effect of moisturizing has been extensively studied in dermatological conditions, such as atopic dermatitis (AD), and has been shown to enhance the efficacy of topical corticosteroids and also prevent disease exacerbation, but this has not been evaluated in patients with psoriasis.[24,25]
The goal of this study was to evaluate the safety and efficacy of a twice-daily regimen of halobetasol ointment (Ultravate®; Ranbaxy Laboratories, Inc.) in combination with ammonium lactate lotion in a consecutive, open-label treatment phase for two weeks followed by a placebo-controlled maintenance phase with twice-daily, everyday, ammonium lactate lotion and weekend-only dosing of twice-daily halobetasol ointment or placebo. Due to the risk of increased cutaneous adverse side effects with prolonged use of superpotent corticosteroids, weekend-only therapy after initial significant clearance should offer an excellent corticosteroid-sparing maintenance option. Further, ammonium lactate lotion has been shown to prevent against cutaneous atrophy and the combination of ammonium lactate lotion with a superpotent topical corticosteroid (halobetasol) should have a protective effect against cutaneous atrophy and help provide increased initial treatment efficacy along with assistance in maintaining lesion clearance.
Patients. This was a randomized, double-blind, placebo-controlled trial conducted at the outpatient clinic of the Mount Sinai School of Medicine Department of Dermatology Clinical Trials Center, in New York, New York, from January 2009 to March 2010. Eligible participants were all adults aged 18 years and older with at least a six-month history of plaque-type psoriasis with a disease severity rated at least “mild” (2) for each of the key psoriasis characteristics (scaling, erythema, plaque elevation/induration). Women of childbearing potential were required to have a negative urine pregnancy test immediately prior to study drug treatment and agree to the use of adequate birth control methods during the entire study. Patients who were pregnant or nursing with a known sensitivity to any of the study drug components, those requiring other medications (topical or systemic) that could affect the course of the disease, those on biological or other systemic treatments for psoriasis in the past three months, those on topical therapies other than emollients in the past one month, and those with pre-existing overt atrophy or telangiectasia in treatment areas were excluded from study participation.
Study objectives and design. Patients were recruited through advertisements (posters, emails, announcements), referrals from the Mount Sinai Dermatology Faculty Practice Associates, and through outside voluntary faculty and rotating dermatology residents. After signing an institutional review board (IRB)-approved informed consent, patients were evaluated for trial eligibility by history and physical examination. A target lesion/location was chosen by the study physician for treatment with an overall BSA ?10 percent. Target lesions/locations were not matched between patients, and the scalp, face, and intertriginous areas were avoided. Clinical assessments including physician global assessment (PGA; the physician’s impression of the disease at a single time point rated as: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe, and 5=very severe) and signs of psoriasis (physician’s assessment of the severity of each of the three key characteristics of psoriatic lesions rated as: 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe, and 5=very severe) were obtained. Digital photography was performed by IRB-approved protocols. Subjects deemed eligible were given both ammonium lactate lotion and halobetasol ointment and instructed on proper application technique. Subjects were directed to place a thin film of halobetasol ointment on each target lesion prior to the application of the ammonium lactate lotion twice daily for two weeks. After two weeks, patients were asked to return with medication for clinical evaluation, photography, and medication accountability. Patients with a lesion score of “clear” (0) or “almost clear” (1) per PGA were randomized in a ratio of 1:1 in a double-blind fashion into one of the following two groups: 1) ammonium lactate lotion twice daily everyday plus halobetasol ointment twice daily on weekends only or 2) ammonium lactate lotion twice daily everyday plus placebo twice daily on weekends only (Figure 1). In order to maintain a double-blind, placebo-controlled maintenance phase, an unblinded study coordinator was trained to dispense the prefilled, identical tubes of halobetasol ointment or placebo at each study visit after medication accountability. The placebo was matched to study drug in appearance, smell, and consistency. For random allocation of the study participants, a computer-generated list (unpredictable sequence) was used to assign patients to treatment groups. The sequence was concealed from the researchers enrolling and assessing study participants. Follow-up assessments were scheduled every four weeks for up to 24 weeks, for total study duration of up to 26 weeks.
Efficacy and safety assessments. Clinical assess-ments including PGA and signs of psoriasis were obtained by study investigators at each study visit along with standardized digital photography of each target lesion. Patients were also required to complete an IRB-approved subject self-assessment, which evaluated on a four-point scale (0=complete disease control, 1=good disease control, 2=limited disease control, and 3=uncontrolled disease) the patient’s perceived extent of psoriatic disease in the treatment area at each study visit. In the open-label phase of the trial (first 2 weeks), all patients were given both medications twice daily and then evaluated for significant disease clearance. Study enrollment required at least an average of “mild” (2) for each of the signs of psoriasis, and the two-week visit required patients to be “clear” (0) or “almost clear” (1) per PGA (an average of 0–1 on the signs of psoriasis) to be randomized into the placebo-controlled maintenance phase of up to an additional 24 weeks. At any time point throughout the maintenance phase, if a target lesion/location assessment scored “mild” (2) or greater by the PGA clinical evaluation, the patient was considered to have disease relapse and was discontinued from study treatment. Safety and efficacy evaluations were performed every four weeks throughout the maintenance phase. The primary efficacy analysis was the percentage of patients achieving a PGA value of “clear” (0) or “almost clear” (1) in the first two weeks of combination treatment as well as at each time point through the maintenance phase compared to baseline (time of randomization). Patients were followed until worsening of the PGA to “mild” (2) or greater or until the final study visit, whichever came first. Secondary efficacy endpoints included changes in subject self-assessment scores, changes in the signs of psoriasis, and the presence of atrophy or telangiectasia at treatment sites. Safety evaluations were conducted through patient history and physical examination, notably a focused skin examination. Adverse events (AEs) were recorded up to the study total of 26 weeks. No follow-up visits were conducted after study treatment concluded.
Statistical analysis. The primary endpoint was a change in PGA during the 24 weeks of the study in the intention-to-treat population (ITT). Secondary efficacy endpoints included changes in subject self-assessment scores, changes in the signs of psoriasis, and the presence of atrophy or telangiectasia at treatment sites for the total 26 weeks of the study. The statistical analyses were performed with SAS Version 9.2 (SAS Institute Inc., Cary, North Carolina). Probabilities of PGA not worsening were estimated using the Kaplan-Meier product limit method with a comparison between treatment group survival curves evaluated by the log-rank test statistic. The Cox proportional hazards model was used to estimate the hazard ratio for worsening of PGA (equivalent to a relative risk adjusted for follow-up time) and a corresponding 95-percent confidence interval. The starting event for the Kaplan-Meier and Cox regression analyses was the two-week visit (time of randomization; represented as 0 weeks on the x-axis) and the terminating event was worsening of PGA (represented as 4-week intervals up to a total of 24 weeks on the x-axis) (Figure 2). All patients were followed from their starting event until their PGA worsened or until their last follow-up visit. If a patient did not worsen, then he or she was censored (marked for analysis) at his or her last visit. Patients who were censored are displayed in the Kaplan-Meier figure with a symbol. For all calculations, the threshold for significance was set at p?0.05. Safety analyses included all patients who received at least one dose of study medication (ITT population). Patients lost to follow up (LTF) were considered to have a probability of disease worsening at their scheduled follow-up visit and were considered discontinued at that study visit.
Secondary outcomes, including subject self-assessment and signs of psoriasis ratings, were analyzed as continuous dependent variables in these statistical models. Mixed modeling analysis of covariance (ANCOVA) was used to compare the relationships between psoriasis symptoms over time in the placebo and steroid treatment groups.
Subject disposition. A total of 57 patients were seen at the screening visit and entered into the open-label portion of the study (Figure 3). Two patients (3.5%, [2 of 57]) failed to return at the two-week study visit and were not included in the efficacy analyses since they were not randomized into the placebo-controlled maintenance phase of the study. The majority of patients (96.5%, [55 of 57]) completed the initial two weeks of the study and was assessed for substantial improvement in lesion characteristics to be considered for randomization into the placebo-controlled maintenance phase. Fourteen patients (25.5%, [14 of 55]) failed to achieve “clear” (1) or “almost clear” (0) by PGA at the two-week study visit and were excluded from the randomization phase of the study. The majority of patients (74.5%, [41 of 55]) had substantial improvement in target lesion characteristics with a documented PGA ?1 and were randomized into the placebo-controlled maintenance portion of the study (Figure 4). Forty-one patients (74.5%, [41 of 55]) were randomized at a ratio of 1:1 to either one of two treatment groups (placebo or steroid). Twenty-one patients (51.2%, [21 of 41]) were randomized to ammonium lactate lotion twice daily everyday with placebo twice daily on weekends only (placebo group). Twenty patients (48.8%, [20 of 41]) were randomized to ammonium lactate lotion twice daily everyday with halobetasol ointment twice daily on weekends only (steroid group). Two patients (total; 4.9%, [2 of 41]) were LTF in the steroid group, but were included in the efficacy analyses since they were randomized to study treatment and had received at least one weekend dosage of placebo-controlled study medication. All patients in the placebo group completed the study.
Efficacy. The primary efficacy endpoint was a change in PGA during the 24-week maintenance phase of the study in the ITT population (Figure 5). Figure 2 demonstrates the probability of worsening of the PGA index for both treatment groups throughout the placebo-controlled maintenance phase. The probability of PGA worsening at four weeks in the steroid group was only 10 percent while in the placebo group the probability rose to 75 percent (p<0.0001). The probability of PGA worsening climbed to 100 percent by 12 weeks in the placebo group while only increasing to 29 percent in the steroid group (p<0.0001). By 20 weeks, the probability of worsening increased and remained at 35 percent in the steroid group. There were 12 patients (steroid group, 57.1%, [12 of 21]) at 24 weeks that still had not worsened. Two patients were LTF in the steroid group (censored as boxes in Figure 2) and were considered to have a probability of disease worsening, and subsequently discontinued, at their scheduled follow-up visit. Since these two patients had received at least one weekend dose of study medication, they were included in the final statistical analysis. Overall, the median time to worsening in the placebo group was four weeks while there was no median time to worsening in the steroid group (at least ?24 weeks) because 50 percent of those patients did not worsen through the course of the placebo-controlled maintenance phase. All patients (100%, [20 of 20]) in the placebo group had a worsening of the PGA index by 12 weeks in the placebo-controlled maintenance phase; while only a minority of patients (42.9%, [9 of 21]) in the steroid group had worsening of the PGA index (Table 1). Worsening of the PGA index was 7.8 times more likely in the placebo group than in the steroid group (p<0.0001). No statistically significant mean time to disease worsening could be calculated as a majority of patients remained in the steroid group at study conclusion. However, nonstatistical mean values of 5.2 weeks (placebo group) and 17.9 weeks (steroid group) can be calculated if one considers the patients remaining (steroid group only, n=12) to be censored at 24 weeks (conclusion of the maintenance phase) and all other patients (steroid and placebo groups, n=29) to be censored at their determined discontinuation visit.
Secondary efficacy endpoints included changes in subject self-assessment scores, changes in the signs of psoriasis, and the presence of atrophy or telangiectasia at treatment sites. To obtain subject self-assessment scores, patients were asked to evaluate the extent of their disease control (disease status) in the preceding days prior to clinical evaluation. The subjects in the placebo group demonstrated higher self-assessment scores (subjectively reported feelings of worse disease status) at every time point compared to those subjects in the steroid group (Figure 6). Overall, there was a statistically significant difference in subject self-assessment scores between the placebo group and steroid group over time in the placebo-controlled maintenance phase of the study (p=0.0368) (Table 2).
Individual changes in the signs of psoriasis were also recorded at each study visit for target lesions. The signs of psoriasis assessments identify the severity of each of the three key characteristics of psoriatic lesions including scaling, erythema, and plaque elevation/induration. Mean scaling, erythema, and plaque elevation/induration scores were much lower in the steroid group compared to the placebo group and there was a statistical difference between groups over time (p<0.0001, p<0.0001, p=0.0180, respectively) (Figure 7, Figure 8, and Figure 9; Table 3,
Table 4, and Table 5).
Safety. There were no reported AEs, including serious AEs, related to study medication throughout the study. No cases of cutaneous irritation, atrophy, or telangiectasia were identified.
Safe and effective long-term treatment and maintenance options are needed for managing the chronic nature of psoriasis to improve patient satisfaction, adherence, and quality of life. In clinical practice, superpotent topical corticosteroids are used as initial therapy to achieve a quick resolution of lesions (improvement to “clear” or “almost clear”) with subsequent reduction of dosage (potency) and/or frequency to maintain this successful early response. To minimize the risks of continued topical corticosteroid use and sustain initial improvement, the authors tested the safety and efficacy of a combination pattern of initial brief application of a superpotent topical corticosteroid (halobetasol ointment) followed by long-term, weekend-only applications to the previously affected sites of psoriasis. Ammonium lactate lotion was added twice daily as an emollient, moisturizer, and keratolytic to create synergy with the halobetasol ointment while optimistically minimizing the risk of corticosteroid-associated cutaneous side effects. The study demonstrated that the combination of ammonium lactate lotion and halobetasol ointment twice daily continually for two weeks had excellent clinical efficacy with no noted adverse effects (Figure 10 A and B). A reduction in the dosing frequency of halobetasol ointment to weekend-only applications (“weekend” therapy or “pulse” therapy) while maintaining twice-daily dosing of ammonium lactate lotion, demonstrated maintenance of initial clinical efficacy for a much longer period of time as compared to weekend-only dosing of placebo (Figure 10 C, D, E).
A number of strategies have been suggested to improve the safety and efficacy of long-term therapy with topical corticosteroids and include the following: 1) using treatment regimens that minimize side effects (weekend-only or “pulse” therapy, dose reduction, or rotating to another therapy), 2) combining topical corticosteroids with other topical agents (vitamin D analogues, tar, tazarotene, salicylic acid, moisturizers), 3) following package insert recommendations (limiting use of superpotent steroids to ?2 weeks), 4) using caution in vulnerable areas (face, intertriginous, or other thin-skinned areas), and 5) using caution in infants, children, and the elderly.26 All of the listed recommendations were utilized in this trial to help minimize side effects while maximizing clinical efficacy.
Weekend-only or “pulse” therapy following successful initial improvement with a superpotent topical corticosteroid has been shown to be extremely valuable in the long-term remission of psoriasis.[27–29] The intention of weekend-only or “pulse” therapy is to prolong remission while minimizing the side effects associated with superpotent topical corticosteroids. Lebwohl et al demonstrated that the use of a second agent (calcipotriene ointment) applied on weekdays (days off of superpotent corticosteroid) to a weekend-only or “pulse” therapy regimen of a superpotent topical corticosteroid (halobetasol ointment) increased the duration of remission in psoriasis. In our study, patients who achieved initial improvement (to “clear” or “almost clear”) on open-label, twice-daily therapy with combination treatment and who were subsequently randomized to the steroid group (weekend-only applications of halobetasol ointment), were able to maintain remission for an extremely longer period of time as compared to those in the placebo group (Figure 2). Our study had limitations, as the placebo-controlled maintenance phase of the study did not have a long enough study duration to capture clinically significant changes in disease status in the steroid group since more than 50 percent of the patients at the end of the 24 weeks still remained in the study. Thus, the best conclusions the authors could draw was that the median time to worsening was four weeks in the placebo group and ?24 weeks in the steroid group.
Modification from continuous, twice-daily applications of both medications after the initial two weeks was made for the following various reasons: 1) package insert limits continuous application of halobetasol ointment to ?2 weeks, 2) to help limit the potential for long-term side effects associated with superpotent topical corticosteroids, and 3) to test, in a placebo-controlled fashion, the weekend-only or “pulse” therapy maintenance regimen. Combination ammonium lactate lotion twice daily everyday with halobetasol ointment or placebo on weekends only was used to help maintain initial efficacy, reduce the incidence of corticosteroid-associated side effects, and to add necessary moisturization and exfoliation considered necessary in inflammatory skin conditions such as psoriasis. Ammonium lactate lotion has been reported to decrease skin atrophy without decreasing the side effects of the superpotent topical corticosteroid clobetasol. Salicylic acid and other keratolytics, such as ammonium lactate lotion, can be used with topical corticosteroids to increase skin penetration and improve clinical response.
Our study confirmed that no incidences of side effects such as cutaneous irritation, atrophy, or telangiectasia were noted in either the steroid group or the placebo group through either phase of the 26-week trial. To limit the incidence of corticosteroid-associated side effects, patients were required to be adults (?18 years of age) with plaque-type psoriasis of the body (not including disease in sensitive skin areas such as the face and/or intertriginous areas); however, topical corticosteroids have been studied in sensitive skin areas and in both children and the elderly with good disease treatment and maintenance.[31,32] Combination treatment of topical corticosteroids and topical calcineurin inhibitors is commonplace in the treatment of AD, but studies in psoriasis are lacking. A recent study of patients with AD demonstrated that the long-term intermittent application of topical calcineurin inhibitors to previously affected skin is more effective at maintaining disease stabilization as compared to vehicle placebo and may be safer.
In general, topical corticosteroid therapy should be initiated with the lowest potency agent that will sufficiently give quick, initial disease control. Avoiding prolonged use with a short initial duration of therapy and then switching to a lower potency topical corticosteroid, decreasing the frequency to twice-weekly or weekend-only or “pulse” therapy, or adding in other agents for maintenance in combination or as a monotherapy, are practical strategies to minimize corticosteroid-related side effects and maximize clinical efficacy and patient satisfaction. Additional studies are needed to further dictate treatment guidelines with superpotent topical corticosteroids in maintenance therapy after initial disease improvement in patients with corticosteroid-responsive inflammatory skin conditions such as psoriasis.
In addition to excellent physician global improvements scores initially (74.5%, [41 of 55]) and in the placebo-controlled maintenance phase, individual lesion characteristics remarkably improved and were sustained throughout the trial in the steroid group (Figure 7, Figure 8, and Figure 9; Table 3,
Table 4, and Table 5). This clinical sustenance may be in part due to ammonium lactate lotion’s moisturizing and keratolytic properties, allowing for the weekend-only dosage of corticosteroid to have enhanced skin penetration and a longer duration of effect. In addition, no corticosteroid-related adverse events were noted in either phase of the study, although this finding can be due either to the addition of the ammonium lactate lotion, which is known to prevent against skin atrophy, or due to the frequency reduction of the halobetasol ointment to weekend-only therapy or a combination of both. Further studies on ammonium lactate lotion’s properties and pathophysiological mechanisms within the skin may help elucidate the authors’ findings.
Subject self-assessment scores improved dramatically following the initiation of both medications twice daily in the open-label phase of the study. On average, in the steroid group, these results were sustained, and in the placebo group, they worsened throughout the placebo-controlled maintenance portion of the study. When analyses were completed comparing PGA to the subject self-assessments and there was a difference, the patient always graded his or her lesions as worse than the physician, signifying there was a discrepancy in disease perception between the subject and the physician. These findings have many implications that could have an impact on a subject’s quality of life, treatment adherence, and treatment expectations. It is already known that many patients with psoriasis have associated comorbidities, such as anxiety and depression, that can lead to poor adherence and treatment outcomes.[34,35] Although the authors believe treatment adherence was paramount through the course of this study, evidence of assessment disagreement in both treatment groups between physician and subject necessitates further studies in this area to determine what factors may be affecting this dissimilarity.
Combination twice-daily ammonium lactate lotion and halobetasol ointment for two weeks effectively cleared plaque psoriasis in approximately 75 percent of patients. Halobetasol ointment weekend-only maintenance therapy in combination with twice-daily ammonium lactate lotion effectively sustained initial improvement for a significantly longer period of time when compared with placebo. No adverse effects, such as cutaneous irritation, atrophy, or telangiectasia, were noted through the study. Although topical corticosteroids are an integral part of the therapeutic treatment options for the treatment of psoriasis and extremely safe when used judiciously in the short term, long-term maintenance regimens incorporating dose or frequency reduction or the addition of a second corticosteroid-sparing agent is the most optimal for successful remissions. Future studies incorporating combination or rotational therapies in the long term will determine guidelines for most advantageous remissions and maintenance thereof.
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