A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis

Background Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. Objectives To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor‐inhibitor therapy. Methods Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5–15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Results In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician’s Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. Conclusions Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.     

Etanercept combined with methotrexate for high-need psoriasis

Background  For some high-need psoriatic patients, the efficacy of etanercept monotherapy is insufficient. In these cases it might be indicated to combine etanercept with other conventional treatments.
Objectives  To provide daily practice safety and efficacy data for etanercept and methotrexate combination therapy.
Methods  Data were extracted from an existing database, which contains prospective safety and efficacy data of all patients who were treated with etanercept in clinical practice. A case was defined as a patient using etanercept and methotrexate simultaneously for an indefinite period during follow-up. For all cases, baseline data, Psoriasis Area and Severity Index (PASI) scores, adverse events and laboratory values were investigated. Furthermore, the influence of introduction and discontinuation of methotrexate on these parameters was analysed.
Results  Fourteen patients with simultaneous use of etanercept and methotrexate were selected. In six patients, methotrexate was introduced after etanercept to avoid further psoriasis deterioration, which resulted in an improvement of psoriasis in four of these patients. Eight patients were on methotrexate therapy before start of etanercept. Discontinuation of methotrexate in six of these patients resulted in a decrease in PASI improvement in five patients. Etanercept combined with methotrexate was well tolerated, and only mild adverse events were reported. No clinically significant changes in laboratory parameters occurred.
Conclusions  Results show that combining etanercept with methotrexate is reasonable when efficacy of etanercept monotherapy is insufficient, or when rapid deterioration of psoriasis after abrupt discontinuation of methotrexate is expected. Laboratory values and adverse events were not different from what would have been expected when using methotrexate alone.     

A multicenter,randomized, open-label pilot trial assessing the efficacy and safety of etanercept 50 mg twice weekly followed by etanercept 25 mg twice weekly,the combination of etanercept 25 mg twice weekly and acitretin,and acitretin alone in patients with moderate to severe psoriasis

Background

Etanercept, a soluble tumor necrosis factor receptor, and acitretin have been shown to be effective in treating psoriasis. Acitretin is widely used in Korea. However, the combination of etanercept plus acitretin has not been evaluated among Korean patients with psoriasis. The objective of this study was to investigate the efficacy and safety of combination therapy with etanercept and acitretin in patients with moderate to severe plaque psoriasis.

Methods

Sixty patients with psoriasis were randomized to receive etanercept 50 mg twice weekly (BIW) for 12 weeks followed by etanercept 25 mg BIW for 12 weeks (ETN-ETN); etanercept 25 mg BIW plus acitretin 10 mg twice daily (BID) for 24 weeks (ETN-ACT); or acitretin 10 mg BID for 24 weeks (ACT). The primary efficacy measurement was the proportion of patients achieving 75 % improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Secondary end points included 50 % improvement in PASI (PASI 50) at week 24 and clear/almost-clear by Physician Global Assessment (PGA) at each visit through week 24.

Results

The proportions of patients achieving PASI 75, PASI 50, and PGA clear/almost-clear at week 24 in the ETN-ETN (52.4, 71.4, and 52.4 %, respectively) and ETN-ACT groups (57.9, 84.2, and 52.6 %, respectively) were higher than in the ACT group (22.2, 44.4, and 16.7 %, respectively). The incidence of adverse events was similar across all arms. This was an open-label study with a small number of patients.

Conclusion

In Korean patients with moderate to severe plaque psoriasis, etanercept alone or in combination with acitretin was more effective than acitretin. All treatments were well tolerated throughout the study.

Trial registration

This study was registered on July 7, 2009 at ClinicalTrials.gov, NCT00936065.

     

Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION)

BACKGROUND: Biologic therapies such as adalimumab, a tumour necrosis factor antagonist, are safe and effective in the treatment of moderate to severe chronic plaque psoriasis. OBJECTIVES: To compare a biologic agent with methotrexate, a traditional systemic agent, to define clearly the role of biologics in psoriasis. METHODS: Patients with moderate to severe plaque psoriasis were randomized to adalimumab (80 mg subcutaneously at week 0, then 40 mg every other week, n=108), methotrexate (7.5 mg orally, increased as needed and as tolerated to 25 mg weekly; n=110) or placebo (n=53) for 16 weeks. The primary efficacy endpoint was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) after 16 weeks. Safety was assessed at all visits through week 16. RESULTS: After 16 weeks, 79.6% of adalimumab-treated patients achieved PASI 75, compared with 35.5% for methotrexate (P<0.001 vs. adalimumab) and 18.9% for placebo (P<0.001 vs. adalimumab). Statistically significantly more adalimumab-treated patients (16.7%) than methotrexate-treated patients (7.3%) or placebo-treated patients (1.9%) achieved complete clearance of disease. The response to adalimumab was rapid, with a 57% improvement in mean PASI observed at week 4. Adverse events were similar across treatment groups. Adverse events leading to study discontinuation were greatest in the methotrexate group, primarily because of hepatic-related adverse events. CONCLUSIONS: After 16 weeks, adalimumab demonstrated significantly superior efficacy and more rapid improvements in psoriasis compared with either methotrexate or placebo.     

Long-term maintenance treatment of moderate-to-severe plaque psoriasis with infliximab in combination with methotrexate or azathioprine in a retrospective cohort

Background  Effective, fast-acting and safe therapies are needed for long-term maintenance treatment of psoriasis. In October 2005, infliximab was approved for the treatment of moderate-to-severe plaque psoriasis, but long-term data are limited.
Objective  To evaluate the effectiveness of infliximab, used in combination with methotrexate or azathioprine, in maintaining clinical benefit in patients with moderate-to-severe psoriasis.
Methods  The medical charts of 23 patients treated with infliximab from August 2001 to February 2007 were retrospectively reviewed. Most patients received either infliximab 3 mg/kg (17 of 23) or 5 mg/kg (1 of 23) in combination with methotrexate, while 5 of 23 patients received infliximab 5 mg/kg in combination with azathioprine. Psoriasis Area Severity Index (PASI) score and adverse events were recorded at every infliximab infusion visit at the hospital.
Results  Patient data were available for a minimum of 4 weeks and up to 5 years and 5 months. At week 14, 91.3% achieved PASI 50, 69.6% achieved PASI 75, and 39.1% achieved PASI 90. Only two patients discontinued therapy due to loss of response: one after 15 months and one after 3 years. All other patients displayed a good clinical response (≥ PASI 50) and were still receiving this regimen at last observation. Combination regimens of infliximab with methotrexate or azathioprine were well tolerated, and only one patient discontinued therapy because of an adverse event (lung embolism) after two infusions with infliximab.
Conclusions  Long-term (> 1 year) maintenance therapy of infliximab combined with methotrexate or azathioprine is effective and well tolerated for moderate-to-severe plaque-type psoriasis.

Conflicts of interest

None declared     

Etanercept

Etanercept (Enbrel), a tumor necrosis factor-alpha antagonist produced by recombinant technology, is approved for use in the US as subcutaneous monotherapy in adults with moderate-to-severe psoriasis who are candidates for systemic therapy or phototherapy. The drug is also indicated in patients with psoriatic arthritis, in whom it may be used in combination with methotrexate. In well designed trials in patients with moderate-to-severe psoriasis, short-term etanercept therapy (typically 25 or 50 mg twice weekly) significantly increased the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score compared with placebo. Similarly, in well designed trials in patients with psoriatic arthritis, treatment with short-term etanercept 25 mg twice weekly, alone or in combination with methotrexate, improved clinical features of the disease, while radiographic progression of joint damage appeared to be significantly slowed in a nonblind 1-year extension. Short-term etanercept therapy was well tolerated in patients with psoriasis or psoriatic arthritis. Etanercept is thus a valuable new option for the treatment of patients with chronic moderate-to-severe plaque psoriasis (who are candidates for systemic therapy or phototherapy or have failed other systemic therapies) or with psoriatic arthritis.     

The efficacy of methotrexate plus pioglitazone vs. methotrexate alone in the management of patients with plaque‐type psoriasis: a single‐blinded randomized controlled trial

Recently, thiazolidinediones have shown to be efficacious with a favorable safety profile when used in the treatment of chronic plaque‐type psoriasis. The aim of this study was to evaluate and compare the efficacy and safety of a combination of methotrexate plus pioglitazone and methotrexate alone in plaque‐type psoriasis. A total of 44 adult patients with plaque‐type psoriasis were included in the study. Patients were randomized to treatment with methotrexate alone (group A) or methotrexate plus pioglitazone (group B) for 16 weeks. The primary efficacy outcome measure was psoriasis area and severity index (PASI) score change between the study groups at week 16 relative to baseline. The secondary efficacy outcome measure was dermatology life quality index (DLQI) score change between the two groups at week 16 relative to baseline. The PASI 75 score was also measured. After 16 weeks of therapy, the percentage of reduction in the mean PASI score was 70.3% in group B and 60.2% in group A. PASI 75 was achieved in 14 patients (63.6%) in group B compared with two patients (9.1%) in group A within 16 weeks, which was significant (P < 0.001). At 16 weeks from the baseline, a 63.6% decrease in the mean DLQI score of group B was seen, while the decrease for group A was 56.9%. Pioglitazone enhances the therapeutic effect of methotrexate in plaque‐type psoriasis, as demonstrated by a reduction in the mean PASI scores. In terms of DLQI, there was no extra benefit by the addition of pioglitazone to methotrexate therapy.     

Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: findings from the LIBERATE study

Background

Apremilast, an oral phosphodiesterase‐4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis.

Objective

To evaluate long‐term efficacy and safety of apremilast in biologic‐naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial.

Methods

Two hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and Severity Index (PASI; 0–72), Scalp Physician Global Assessment (ScPGA; 0–5) and Nail Psoriasis Severity Index (NAPSI; 0–8); patient‐reported outcomes (PROs) were assessed using the Dermatology Life Quality Index (DLQI; 0–32) and pruritus visual analog scale (VAS; 0–100 mm).

Results

The apremilast‐extension phase (Weeks 16–104) included 226 patients in the placebo/apremilast (n = 73), apremilast/apremilast (n = 74) and etanercept/apremilast (n = 79) groups, and at Week 104, 50.7%, 45.9% and 51.9% of these patients, respectively, maintained ≥75% reduction from baseline in PASI score (based on last‐observation‐carried‐forward analysis). Across treatment groups, ScPGA 0 (clear) or 1 (minimal) was achieved by 50.0%–59.2% of patients; NAPSI mean change from baseline was ?48.1% to ?51.1%; DLQI score ≤5 was achieved by 66.0%–72.5% of patients; and pruritus VAS mean change from baseline was ?24.4 to ?32.3. AEs in ≥5% of patients (diarrhoea, nausea, nasopharyngitis, upper respiratory tract infection and headache) did not increase with prolonged apremilast exposure.

Conclusions

Apremilast demonstrated significant and sustained improvements in skin, scalp, nails and PROs (pruritus and quality of life) over 104 weeks in patients with moderate to severe plaque psoriasis. Safety was consistent with the known safety profile of apremilast.

     

Sequential treatment with biologics: switching from efalizumab to etanercept in 35 patients with high‐need psoriasis

Background Use of biological agents has been shown to be an efficacious approach in psoriasis, when traditional treatments fail. However, there are limited data on the effectiveness and safety of switching from one biological agent to another. Objectives We aimed to evaluate the effectiveness and safety of etanercept as a sequential treatment in patients previously treated with efalizumab, and to evaluate different transition strategies from efalizumab to etanercept. Methods We present a retrospective study in patients with high‐need plaque psoriasis who were unable to continue efalizumab and were immediately switched to etanercept. Results We included 35 patients during a 4.5‐year period. At 24 weeks of etanercept therapy, 57% of patients had a PASI reduction of 75%, suggesting that alternating between biological agents is feasible. We used three different switching approaches: (i) etanercept in combination with cyclosporine as bridge therapy, (ii) etanercept in combination with methotrexate as bridge therapy, (iii) etanercept monotherapy. Combination therapy was efficacious in all patients, including eight patients with rebound phenomenon with efalizumab. Etanercept was discontinued in two patients as a result of serious adverse events that consisted of an oral squamous cell carcinoma and a diffuse B‐cell‐non‐Hodgkin lymphoma. Conclusions In our experience, it seems that etanercept alone may not be sufficient when transitioning from efalizumab in high‐need patients with severe worsening or rebound of psoriasis. In such patients, combination of etanercept with cyclosporine or methotrexate is a more effective approach. Non‐response to efalizumab did not preclude clinical response after switching to etanercept.     

Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis

Methotrexate, an inexpensive first-line systemic therapy for moderate-to-severe psoriasis, is limited in its use by unpredictable efficacy and toxicity. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in methotrexate transmembrane transporters and adenosine receptors are associated with efficacy and/or toxicity of the drug. DNA was collected from 374 patients with chronic plaque psoriasis who had been treated with methotrexate. Phenotypic data on efficacy and toxicity were available. Haplotype tagging SNPs (r(2)>0.8) across the relevant genes, with a minor allele frequency of >5%, were selected from the HAPMAP phase II data. SNPs within the efflux transporter genes ABCC1 (ATP-binding cassette, subfamily C, member 1) and ABCG2 (ATP-binding cassette, subfamily G, member 2) are associated with good response to methotrexate therapy in patients with psoriasis; the former gene was also associated with the onset of toxicity. With one SNP in ABCC1, rs246240, the carriage of two copies of allele 1 gives an odds ratio of 2.2 (95% confidence interval: 1.3-3.6; P=0.001) for developing toxicity to methotrexate. These data indicate that knowledge of SNPs in genes relevant to methotrexate efflux may be important in selecting patients suitable for this therapy.     

Systemic methotrexate treatment in childhood psoriasis: further experience in 24 children from India

Well-designed studies on systemic therapeutic modalities for severe psoriasis in children are rare. Children with severe disease are treated with the support of data extrapolated from that in adult, although management in them differs from adults in several important aspects. Like other systemic modalities, data regarding the use of methotrexate in the treatment of childhood psoriasis is meager. This study aims to analyze the efficacy and safety of methotrexate in severe or disabling childhood psoriasis. The records of all the patients <18 years of age treated with systemic methotrexate at the psoriasis clinic of our institute from January 1993 to December 2006 were retrieved. Information regarding demographic profile, disease characteristics, response to treatment, side effects, etc. was noted from predesigned clinic proforma. Indications of methotrexate use were baseline psoriasis area and severity index (PASI) >10, disease refractory to conventional therapies and disabling psoriasis even though the psoriasis area and severity index was <10. Clinical status of patients was assessed at weekly intervals for the first 2 weeks, fortnightly during next month and then monthly. Response to therapy was graded as good (50-75% decrease in PASI) and excellent (>75% decrease in PASI). Laboratory investigations to detect methotrexate induced toxicity were performed at regular intervals. Of the 29 patients treated with methotrexate, 24 were eligible for the final data analysis. Indication for the institution of methotrexate therapy was severe disease, viz., extensive recalcitrant plaque type psoriasis in 17 patients, erythroderma and generalized pustular psoriasis of von-Zumbusch type in three patients each and severe disabling palmo-plantar involvement along with chronic plaque lesions in one patient. Response to therapy was excellent (>75% decrease in PASI) in all but two patients. The mean time to control the disease, i.e., 50% reduction in PASI was 5.1 weeks. Mean total cumulative dose of methotrexate in the first episode was 215 mg. The duration of remission could be calculated in nine patients only, varying from 1.5 months to 3 years. Side effects were mild, observed in nine children, which included nausea, vomiting, and loss of appetite. Methotrexate is an effective, cheap, easily available, and reasonably safe drug to be used in severe childhood psoriasis under an expert supervision and laboratory monitoring.     

Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque‐type psoriasis – a randomized single‐blinded placebo‐controlled study

Background Psoriasis is a chronic, recurring inflammatory disease affecting the skin, joints and nails that has a significant negative impact on the quality of life. Efficacy of combination of methotrexate/narrowband ultraviolet B (NBUVB) phototherapy in the treatment of psoriasis has been rarely assessed. Objectives To compare the efficacy of methotrexate/NBUVB phototherapy combination vs. NBUVB phototherapy in the treatment of chronic plaque psoriasis. Methods Forty patients with chronic plaque‐type psoriasis (body surface area involvement >10%) were randomized to receive either methotrexate/NBUVB phototherapy (group A) or placebo/NBUVB phototherapy (group B). End point of treatment was 75% reduction in Psoriasis Area and Severity Index (PASI) Score or upto 6 months, whichever was earlier. Patients were then followed up for a period of 12 weeks for assessment of relapse. Results Of 40 patients, 37 completed the treatment period and 29 both the treatment period and follow‐up. PASI 75 was achieved in 19/20 patients in group A and 14/20 patients in group B (P < 0.04). The mean number of weeks(P = 0.001), the mean cumulative dose of NBUVB (P = 0.001) and the mean number of phototherapy sessions (P = 0.0001) required to achieve PASI 75 were significantly less in group A compared with group B. There was no significant difference in the number of patients who relapsed during the follow‐up period (P = 0.68). Conclusion Combination of methotrexate and NBUVB phototherapy provides more rapid clinical improvement compared with NBUVB monotherapy in the treatment for chronic plaque‐type psoriasis.     

Topical methotrexate therapy for psoriasis

In vitro percutaneous penetration of methotrexate is enhanced with 1-dodecylazacycloheptan-2-one (laurocapram [Azone]). Laurocapram-containing methotrexate formulations provide effective local inhibition of epidermal DNA synthesis in the in vivo hairless mouse and minipig models, providing the biochemical rationale for topical use in the treatment of psoriasis. Topical methotrexate (0.1%, 0.5%, and 1%) in a laurocapram-containing formulation was tested in a two-center double-blind pilot clinical study of 42 patients with plaque psoriasis. Drugs were applied twice a day for six weeks, and lesions were scored weekly for erythema, scale, and elevation. An overall improvement of 50% or more in the combined scores for erythema, scale, and elevation was obtained with 0.1% methotrexate (64% of patients), 0.5% methotrexate (59%), and 1% methotrexate (56%) vs the vehicle alone (25%). These preliminary findings suggest that methotrexate preparations that provide adequate percutaneous absorption may have a beneficial effect in the treatment of psoriasis.     

Patient-reported outcomes of psoriasis improvement with etanercept therapy: results of a randomized phase III trial

BACKGROUND: Etanercept, a soluble tumour necrosis factor receptor, lessens the severity of psoriasis as measured by physician-reported clinical outcomes. Equally important is the patient perspective on the effect of etanercept therapy on daily life. OBJECTIVES: To assess patient-reported outcomes (PROs) in patients with psoriasis receiving etanercept therapy. METHODS: In this multinational, randomized, phase III trial, patients with psoriasis received placebo (n = 193), etanercept 50 mg per week (n = 196) or etanercept 50 mg twice weekly (n = 194) during the initial 12-week, double-blind period. Thereafter, all patients received open-label etanercept (50 mg per week). The following PROs were assessed: Dermatology Life Quality Index (DLQI), Short Form-36 Health Survey (SF-36), patient rating of pruritus, and patient global assessment of psoriasis. RESULTS: At week 12, DLQI total score improved by 65-70% in patients receiving etanercept compared with 6% in patients receiving placebo (P < 0.0001), and improvement in DLQI was clinically meaningful (> or = 5-point improvement or 0 score) for 72-77% of patients receiving etanercept therapy. All DLQI and SF-36 subscales and the SF-36 physical and mental component summary scores demonstrated significantly greater improvement with etanercept therapy than with placebo, illustrating that etanercept benefits patients with psoriasis across multiple domains that contribute to health-related quality of life. With etanercept therapy, distributions of patient ratings of pruritus and global assessment of disease shifted from moderate to severe (baseline) to minimal to good (week 12). Etanercept-induced benefits of PROs were maintained for patients who reduced their dose after 12 weeks. CONCLUSIONS: Etanercept therapy improves PROs in patients with psoriasis and makes a meaningful difference to their lives. These results support the efficacy profile of physician-reported clinical measures while providing a more complete understanding of the benefits experienced by patients with psoriasis treated with etanercept.     

Comparative therapeutic evaluation of different topicals and narrow band ultraviolet B therapy combined with systemic methotrexate in the treatment of palmoplantar psoriasis

Background:

The incidence of uncomplicated psoriasis is 1–3% in the general population. The involvement of palm and sole is seen in 7–14.5% of cases. There are different topicals and systemic therapies available for treating the case of psoriasis but none is satisfactory for longer duration.

Aim:

The study involved the comparative therapeutic evaluation of the different topical regimens and narrow band ultraviolet B (NB-UVB) therapy in combination with systemic methotrexate.

Materials and Methods:

The study was held in out-patient department of Skin, VD and Leprosy of B.R.D. Medical College, Gorakhpur, from July 2007 to December 2008. The group included 98 new cases of palmoplantar psoriasis. These cases were divided into eight groups according to the eight regimens involved in the study. The severity of psoriasis was assessed by the ESIF (erythema, scaling, induration and fissuring) score.

Results:

The study showed that all the regimens had significant response rates. The combination of NB-UVB with systemic methotrexate had maximum response rate (64.85±4.52%) that was statistically significant (paired “t” at 16d.f. = 33.329, P<0.001) with minimum number of recurrences after stopping the treatment. The combination of halobetasol ointment with systemic methotrexate also had significant response rate (paired “t” at 19d.f. = 13.5183, P<0.001) but had maximum number of cases with recurrence (70%) after stopping the treatment.

Conclusion:

These results suggest that the combination of every regimen with systemic methotrexate resulted in an early and a good improvement in the quality of life of patients suffering from psoriasis. It also shows that NB-UVB in combination with systemic methotrexate is more efficacious and has minimum recurrence rate and side effects in the treatment of palmoplantar psoriasis.     

Efficacy and safety of methotrexate in alopecia areata

BACKGROUND

Alopecia areata is a chronic disorder of the hair follicles and nails, of unknown etiology, with clear autoimmune components and genetic factors. Several therapeutic options have been suggested; however, no treatment is able to modify the disease course. Methotrexate is an immunosuppressant used in various dermatoses and recently introduced as a therapeutic option for alopecia areata.

OBJECTIVES

To evaluate the efficacy and safety of methotrexate in alopecia areata.

METHODS

In a retrospective, non-controlled study, we evaluated 31 patients with alopecia areata in current or prior treatment with methotrexate to assess the therapeutic response according to sex, age, pattern of alopecia areata, disease duration, cumulative dose of methotrexate, use of systemic corticosteroids or other treatments, and drug safety.

RESULTS

Regrowth greater than 50% was observed in 67.7% of patients, with the best responses observed in those with <5 years of disease progression (79%), age over 40 years (73.3%), male patients (72.8%), cumulative dose of methotrexate 1000-1500 mg, and multifocal alopecia areata (93%). Among patients receiving systemic corticosteroids in combination with methotrexate, 77.3% had greater than 50% regrowth, compared with 44.4% in those who used methotrexate alone. The therapeutic dose ranged from 10-25 mg/week. No patient had serious adverse effects. Relapse was observed in 33.3% of patients with more than 50% regrowth.

CONCLUSION

Methotrexate appears to be a promising and safe medication for the treatment of severe alopecia areata when used alone or in combination with corticosteroids.     

Effect of methotrexate on serum levels of IL-22 in patients with psoriasis

Interleukin-22 (IL-22) is the effector molecule of T-helper subset 22 (Th-22) lineage that promotes keratinocyte proliferation and dermal inflammation in psoriasis. Methotrexate is widely used as a first-line treatment in moderate to severe psoriasis. Methotrexate inhibits inflammatory and cytokinetic processes via various mechanisms, but the relevance of these to psoriasis is limited and whether methotrexate is specifically able to down-regulate Th22 cytokines is unknown. To determine if methotrexate reduces IL-22 in cases of psoriasis. Nineteen patients with moderate to severe psoriasis were given methotrexate 15 mg per week for up to 12 weeks. Serum levels of IL-22 were determined by enzyme-linked immunosorbent assay (ELISA) before and after treatment. Eleven of 19 patients (57.8%) achieved a 75% PASI score reduction. IL-22 levels were significantly higher in untreated psoriasis patients (56.63 ± 60.73 pg/mL) than in controls (12.58 ± 12.59 pg/mL). Methotrexate significantly reduced serum levels of IL-22 in psoriasis patients to 5.91 ± 7.97 pg/mL (p<0.001). Moreover, there was a significant positive correlation between IL-22 levels and PASI (r=0.63, p=0.004). Methotrexate significantly reduces serum IL-22 levels in cases of psoriasis. This is a novel mechanism by which methotrexate acts in the treatment of this disease.     

Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms

Background  The use of methotrexate is limited by interindividual variability in response. Previous studies in patients with either rheumatoid arthritis or psoriasis suggest that genetic variation across the methotrexate metabolic pathway might enable prediction of both efficacy and toxicity of the drug.
Objectives  To assess if single nucleotide polymorphisms (SNPs) across four genes that are relevant to methotrexate metabolism [folypolyglutamate synthase ( FPGS ), gamma-glutamyl hydrolase ( GGH ), methylenetetrahydrofolate reductase ( MTHFR ) and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase ( ATIC )] are related to treatment outcomes in patients with psoriasis.
Methods  DNA was collected from 374 patients with psoriasis who had been treated with methotrexate. Data were available on individual outcomes to therapy, namely efficacy and toxicity. Haplotype-tagging SNPs ( r ² > 0·8) for the four genes with a minor allele frequency of > 5% were selected from the HAPMAP phase II data. Genotyping was undertaken using the MassARRAY spectrometric method (Sequenom^®).
Results  There were no significant associations detected between clinical outcomes in patients with psoriasis treated with methotrexate and SNPs in the four genes investigated.
Conclusions  Genetic variation in four key genes relevant to the intracellular metabolism of methotrexate does not appear to predict response to methotrexate therapy in patients with psoriasis.     

Effects of etanercept treatment on lipid profile in patients with moderate-to-severe chronic plaque psoriasis: a retrospective cohort study

Treatment with tumor necrosis factor alpha (TNF-α) inhibitors may have favourable effects on the lipid profile. This is the first study to assess the impact of etanercept on the lipid profile in patients with moderate-to-severe plaque psoriasis. To investigate the effect of etanercept on the lipid profile after 24 weeks of treatment in patients with moderate-to-severe plaque psoriasis. We conducted a retrospective cohort study reviewing the medical records of 45 consecutive patients who were treated for psoriasis with etanercept between June 2006 and September 2009. Demographic and clinical data were collected. Levels of total cholesterol, LDL-C, HDL-C, triglycerides, fasting glucose and C-reactive protein were recorded at the start of etanercept and at week 24. Levels of total cholesterol, LDL-C and triglycerides increased after 24 weeks of treatment with etanercept, with mean differences of 7.1 mg/dL (p=0.505), 2.0 mg/dL (p=0.718) and 2.8 mg/dL (p=0.180), respectively. HDL-C decreased, with a mean difference of -1.4 mg/dL (p=0.995). None of these changes were statistically significant. We found no favourable changes on the lipid profile after 24 weeks of treatment with etanercept in responding patients with chronic plaque psoriasis.     

A Clinical Trial of Combination Therapy with Etanercept and Low Dose Cyclosporine for the Treatment of Refractory Psoriasis

Background

Over the past decade, combination therapies have become a mainstay of dermatologic care in psoriasis. Combination therapies are often more effective and safer than large dose single-agent therapies. With the emergence of new biologic therapies, dermatologists now have a wider array of tools to treat psoriasis. Although much data exists regarding cyclosporine or biologic agents alone for psoriasis, little is known about the efficacy, safety and tolerability of combination regimens.

Objective

We designed a study to evaluate the efficacy and safety of etanercept and cyclosporin combination therapy in patients with refractory psoriasis.

Methods

We administered oral cyclosporine (200 mg daily) and subcutaneous etanercept 50 mg weekly injections until symptoms improved, then maintained treatment at a reduced dose. Seven patients with refractory psoriasis were evaluated 4 weekly.

Results

All 7 patients showed rapid responses to combination therapy. Mean Psoriasis Area and Severity Index reductions following conditioning therapy (mean: 6.85 weeks) and maintenance therapy (mean: 56.5 weeks) were 94.9% and 93.2%, respectively.

Conclusion

Etanercept and low-dose cyclosporine combination therapy appears to be a safe and efficacious alternative treatment strategy for patients with refractory psoriasis. The combination induced rapid improvement in patients with refractory psoriasis and dramatically improved their quality of life. Clinical studies including larger patient cohort are required to validate the safety and efficacy of this combination therapy.