银屑病患者抗肿瘤坏死因子α治疗前后血清抗核抗体、抗dsDNA抗体及抗ENA抗体的变化

目的：观察银屑病患者接受抗肿瘤坏死因子α制剂治疗后抗核抗体（ANA）、抗dsDNA抗体和抗可提取性核抗原（ENA）抗体的变化。方法回顾分析32例银屑病患者,其中13例使用英夫利西单抗治疗,19例使用依那西普治疗。英夫利西单抗组第0、2、6周各用药1次,此后每隔8周用药,于每次用药前检测患者ANA、抗dsDNA抗体及ENA的情况和临床症状的变化。依那西普组每周用药2次,每3~6个月检测患者ANA、抗dsDNA抗体及ENA的情况和临床症状的变化。采用银屑病皮损面积和严重度指数（PASI）75、疾病活动评分（DAS）28评估临床疗效,间接免疫荧光法检测血清ANA水平,免疫印迹法和ELISA法检测抗dsDNA抗体水平,免疫印迹法检测抗ENA抗体水平。结果32例银屑病患者临床症状有不同程度缓解。32例抗TNF?α治疗的患者中有7例（21.9%）出现自身抗体,其中英夫利西单抗组中4例治疗（8.3±5.1）个月后出现自身抗体,3例ANA阳性,3例ENA阳性;依那西普组中3例治疗（9.0±3.0）个月后出现自身抗体,3例ANA阳性,1例ENA阳性。结论部分银屑病患者接受抗肿瘤坏死因子α制剂治疗后可出现自身抗体。     

Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris

Background Adherence to treatment is an indicator of treatment success. Long‐term data on adherence to biologic treatment in psoriasis are lacking. Objectives To compare the tumour necrosis factor (TNF)‐α inhibitors regarding drug survival rate and safety in patients with psoriasis. Methods This study is based on data from the Danish nationwide database DERMBIO covering patients with psoriasis treated with a biologic agent. All patients who received anti‐TNF‐α treatment in academic referral centres were included. Baseline data, adverse events, time on treatment and reason for stopping treatment were recorded. Hazard ratios (HRs) for factors determining drug survival were calculated by logistic regression. Results In total, 882 treatment series with etanercept (n = 311), adalimumab (n = 427) or infliximab (n = 144) were administered to 747 patients. Significant predictors of drug survival were: sex, the anti‐TNF‐α agent and the previous response to an anti‐TNF‐α agent. In the group of anti‐TNF‐α‐naïve patients the longest drug survival was observed for infliximab, followed by adalimumab [HR vs. infliximab 3·70, 95% confidence interval (CI) 1·99–6·89] and etanercept (HR vs. infliximab 3·18, 95% CI 1·72–5·86). The 4‐year drug survival is in the range of 40% for etanercept or adalimumab vs. 70% for infliximab. There was no difference in number of adverse events. Conclusions The overall efficacy of anti‐TNF‐α drugs diminishes with time, as envisaged by the progressive loss of patient adherence to treatment. The major reasons for stopping treatment were loss of efficacy, followed by adverse events. Infliximab had the best patient retention ability, with 70% of patients still being on the drug after 4 years of treatment.     

Antinuclear antibodies associate with loss of response to antitumour necrosis factor‐α therapy in psoriasis: a retrospective,observational study

Background An increasing number of patients with severe psoriasis are failing to respond to antitumour necrosis factor (TNF)‐α therapy (etanercept, infliximab and adalimumab). Objectives We observed that many of these patients developed antinuclear antibodies (ANA) and antidouble‐stranded DNA (anti‐dsDNA) antibodies while on treatment prompting us to investigate whether their development is associated with anti‐TNF treatment failure. Methods All patients with psoriasis who had received anti‐TNF therapies were identified and their blood results and treatment histories were obtained from electronic patient records and case notes. Results A total of 97 patients had been treated with anti‐TNF agents (60 were on their first agent, 22 had been on and stopped one agent, nine had been on and stopped two agents and six had been on and stopped all three agents). ANA developed in 17% of patients on their first treatment, 54% of patients who had failed one treatment, 78% of patients who had failed two treatments and 83% of patients who had failed all three treatments. Anti‐dsDNA antibodies developed in 2%, 27%, 33% and 83% of patients from the same respective groups. Significantly, the antibodies developed before treatment had failed with all three agents and their development was not related to the total time that patients had been on anti‐TNF therapy. Conclusions This study suggests that the development of ANA and anti‐dsDNA antibodies on anti‐TNF treatment may act as a marker of forthcoming treatment failure. Large‐scale prospective studies are required to assess the importance of this observation.     

Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1)

Background Infliximab is indicated for treatment of moderate‐to‐severe plaque psoriasis in adults whose disease cannot be controlled with other systemic therapies, including methotrexate (MTX). To date, no studies have directly compared the efficacy and safety of infliximab and MTX. Objectives To compare the efficacy and safety of infliximab vs. MTX in adults with moderate‐to‐severe plaque psoriasis. Methods MTX‐naïve patients (n = 868) were randomized 3 : 1 to receive infliximab 5 mg kg^?1 at weeks 0, 2, 6, 14 and 22 or MTX 15 mg weekly with a dose increase to 20 mg weekly at week 6 if the Psoriasis Area and Severity Index (PASI) response was < 25%. At week 16, patients with < PASI 50 response could switch treatment groups. The primary efficacy endpoint was PASI 75 response at week 16. Major secondary efficacy endpoints were PASI 75 response at week 26, and the proportion of patients achieving a Physician’s Global Assessment (PGA) score of cleared (0) or minimal (1) at weeks 16 and 26. Others included Dermatology Life Quality Index, 36‐Item Short Form Health Survey, and PGA, PASI 50, PASI 75 and PASI 90 responses over time. Results The primary endpoint was achieved by a significantly greater proportion of infliximab‐treated patients (508/653, 78%) than MTX‐treated patients (90/215, 42%; P < 0·001). Key secondary endpoints also were achieved by a greater proportion of infliximab‐treated patients. Similar responses were observed at week 26 in patients who switched from MTX to infliximab at week 16. Overall adverse event (AE) incidence was comparable between groups, but incidence of serious and severe AEs was slightly higher in the infliximab group. Conclusions Infliximab was well tolerated and more efficacious than MTX in patients with moderate‐to‐severe plaque psoriasis. Infliximab also was efficacious in patients who failed MTX and switched to infliximab.     

Infliximab partially impairs the anti‐Mycobacterium tuberculosis immune responses of severe psoriasis patients with positive tuberculin skin‐test

Background Infliximab and etarnecept are now widely used for treating severe psoriasis. However, these drugs, especially infliximab, increased the risk of tuberculosis reactivation. Surprisingly, epidemiological data suggest that the tuberculosis rate in patients taking infliximab in São Paulo State, Brazil, is similar to that of some developed, non‐endemic countries. Objective The aim of this study was to better understand the effect of infliximab on Mycobacterium tuberculosis (Mtb) immune responses of psoriasis patients in an endemic setting (Brazil). Methods We evaluated the tuberculosis‐specific immune responses of severe psoriasis patients and healthy individuals, both tuberculin skin test (TST) positive, in the presence/absence of infliximab. Patients had untreated severe psoriasis, no co‐morbidities affecting the immune responses and a TST >10 mm. Healthy TST⁺ (>10 mm) individuals were evaluated in parallel. PBMC cultures from both groups were stimulated with different Mycobacterium tuberculosis (Mtb) antigens (ESAT‐6, 85B and Mtb lysate) and phytohemagglutinin, with or without infliximab (5 μg/mL). Parameters evaluated were TNF‐α, IFN‐γ and IL‐10 secretion by ELISA, overnight IFN‐γ ELISpot and lymphocyte proliferative response (LPR). Results Infliximab almost abolished TNF‐α detection in PBMC supernatants of both groups. It also significantly reduced the LPR to phytohemagglutinin and the Mtb antigens as well as the IFN‐γ levels secreted into day 5 supernatants in both groups. There was no concomitant exaggerated IL‐10 secretion that could account for the decreases in these responses. ELISpot showed that, contrasting with the central‐memory responses above, infliximab did not affect effector‐memory INF‐γ‐releasing T‐cell numbers. Conclusions Infliximab affected some, but not all aspects of the in vitro antituberculosis immune responses tested. The preserved effector‐memory responses, putatively related to exposure to environmental mycobacteria, may help to explain the lower than expected susceptibility to tuberculosis reactivation in our setting.     

Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial

Background Psoriasis is a chronic disease that significantly diminishes the health‐related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor α monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. Objectives The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. Methods In this double‐blind, placebo‐controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg^?1 of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. Results Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3‐ and 5‐mg kg^?1 groups showed a median percentage improvement in DLQI scores of 84·0% and 91·0%, respectively, compared with 0% in the placebo group (P < 0·001). The median decrease from baseline in DLQI score at week 10 was 8·0 and 10·0 for the 3 and 5 mg kg^?1 infliximab groups, respectively, compared with 0 in the placebo group (P < 0·001). Thirty‐three per cent and 40% of patients in the 3 and 5 mg kg^?1 infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0·001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0·61, P < 0·001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50–75% improvement in PASI during the same period (60%). Conclusions Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe psoriasis.     

Infliximab for the treatment of psoriasis in the U.K.: 9 years' experience of infusion reactions at a single centre

Background Infliximab is an antitumour necrosis factor‐α chimeric monoclonal antibody that is an established treatment for severe chronic plaque psoriasis. The recommended administration of a 2‐h infusion followed by 2 h of monitoring is practised due to the potential occurrence of infusion reactions. However, accelerated infusions and shortened monitoring periods are used in patients with rheumatological disorders and inflammatory bowel disease without an increase in adverse events. Objectives To review the standard infliximab infusion protocol, the incidence of acute infusion reactions, the use of concomitant methotrexate and the clinical relevance of the 2‐h postinfusion monitoring period. Methods A retrospective case note and pharmacy database review of all infliximab infusions administered to patients with psoriasis at a tertiary dermatology centre was carried out. Results Fifty‐nine consecutive patients received a total of 858 infliximab infusions (range 1–43 infusions per patient) between January 2001 and June 2010. The incidence of infusion reactions was 1·5%, affecting 16·9% of patients and occurring between the first and eleventh infusions. Mild, moderate and severe acute reactions occurred in 0·6% (n = 5), 0·3% (n = 3) and 0·3% (n = 3) of infliximab infusions, respectively. Thirty‐three patients (56%) received concomitant systemic treatments during part of or throughout the infliximab treatment, including 24 (41%) on methotrexate (5–20 mg weekly). The prevalence of infusion reactions in patients receiving infliximab alone was 27% compared with 4% in those receiving concomitant methotrexate (P = 0·05). All infusion reactions were managed as per our trust protocol with only one infusion reaction occurring in the postinfusion period (10 min after infusion completion). Conclusion The risk of infusion reactions in our cohort of patients was low, with the majority occurring early in the treatment cycle. Concomitant methotrexate may reduce this risk. A shortened postinfusion monitoring period can be safely considered.     

A follow-up study in 28 patients treated with infliximab for severe recalcitrant psoriasis: evidence for efficacy and high incidence of biological autoimmunity

BACKGROUND: Infliximab, an antitumour necrosis factor-alpha chimeric monoclonal antibody, is effective for the treatment of severe psoriasis. While the induction of antinuclear antibodies (ANA) and antidouble-stranded-DNA antibodies (anti-dsDNA-ab) is frequently observed in patients with rheumatoid arthritis and Crohn disease receiving infliximab, the incidence of induced biological and clinical autoimmunity remains unknown in the context of psoriasis. OBJECTIVES: To investigate biological and clinical signs of autoimmunity in 28 patients receiving infliximab for severe, recalcitrant forms of psoriasis, and the clinical response to treatment. METHODS: Twenty-eight patients, 15 men and 13 women (median age 39.4 years) with psoriasis refractory to three or more systemic treatments were included. Twenty presented with plaque-type psoriasis [median Psoriasis Area and Severity Index (PASI) score 25.9; range 7.2-48], five with psoriatic erythroderma (median PASI score 54; range 48-72) and three with generalized pustular psoriasis (GPP). Psoriatic arthritis was present in 13 patients (46.4%). Infliximab 5 mg kg(-1) was given at week (W) 0, W2, W6 and every 8 weeks thereafter. Clinical data were assessed at baseline and before each infusion. Detection of ANA and of IgM and IgG anti-dsDNA-ab were performed at baseline and at W22 by immunofluorescence and enzyme-linked immunosorbent assay, respectively. RESULTS: The mean number of infliximab infusions was 5.5 (range 2-15). Among patients with plaque-type and erythrodermic psoriasis, 17 of 25 (68%) and three of five reached a PASI improvement of 75% or more, respectively, while rapid improvement of clinical and biological signs was observed in all three patients with GPP. The prevalence of positive detection of ANA raised from 12% at baseline to 72% at W22 (P = 0.0001), an increase which was also observed for IgM anti-dsDNA-ab (68% vs. 0%, P < 0.0001), while no significant change was observed for the IgG isotype (16% vs. 0%, P = 0.125). Three patients developed nonerosive polyarthritis, without any other criteria for systemic lupus. CONCLUSIONS: The incidence of biological autoimmunity is high in patients with refractory psoriasis receiving infliximab. The concomitant onset of polyarthritis in three cases raises the need to investigate the incidence of autoimmune manifestations in psoriatic patients receiving infliximab in further large-scale studies.     

Therapeutic Hotline: Re‐induction may be useful to manage psoriasis relapse during long‐term maintenance treatment with infliximab: a retrospective analysis

Infliximab is an anti‐tumor necrosis factor‐alpha monoclonal antibody that is highly effective for the treatment of psoriatic disease. During maintenance treatment, some patients may experience a disease relapse, and, in such circumstances, dose intensification is frequently used to regain efficacy. We report our cumulative experience on the use of infliximab re‐induction in patients whose psoriasis relapsed during long‐term maintenance treatment with infliximab. From September 2005 to January 2009, 22 patients required re‐induction because of a relapse of their psoriasis. Re‐induction was effective in restoring response in most patients and was well tolerated in all cases, without occurrence of serious or unexpected adverse events.     

Anti–tumour necrosis factor-α therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study

Background Chronic plaque psoriasis is associated with overweight or obesity. Anti–tumour necrosis factor‐α (anti‐TNF‐α) treatments are now frequently used in psoriasis management. TNF‐α is deeply involved in body weight homeostasis, which may be affected by TNF‐α–targeted therapy. Objective To investigate whether anti‐TNF‐α treatments is associated with changes in body weight in patients with chronic plaque psoriasis. Methods We performed a retrospective controlled analysis comparing the variations in body weight and body mass index (BMI) in three closed cohorts of psoriatic patients during a 6‐month treatment with etanercept (N = 58), infliximab (N = 40) or methotrexate (N = 43). Results We observed a body weight increment of 1.5 ± 2.7 kg (mean ± SD; P = 0.0002) and 2.5 ± 3.3 kg (P = 0.004) in patients treated with etanercept and infliximab, respectively. In contrast, a non‐significant change (0.6 ± 1.4 kg; P = 0.4) was measured in patients treated with methotrexate. The BMI increased with 0.5 ± 0.5 (P = 0.01) and 0.8 ± 1 (P = 0.003) points in patients treated with etanercept and infliximab, respectively, whereas it did not change (< 0.2 ± 0.5; P = 0.06) in patients treated with methotrexate. About one fourth of patients experienced a 4‐ to 10‐kg weight gain. Differences in body weight variations among patients treated with anti‐TNF‐α therapies and methotrexate were statistically significant (P = 0.0005). We could not identify clinical parameters predicting this phenomenon. Conclusions Patients with psoriasis treated with long‐term anti‐TNF‐α therapies may manifest a body weight gain. This effect should be taken into account in the global approach to patients with psoriasis.     

Treatment of palmoplantar psoriasis with infliximab: a randomized,double‐blind placebo‐controlled study

Background Palmoplantar psoriasis is a difficult to treat variant of plaque psoriasis. Objective To study the safety and efficacy of infliximab in non‐pustular palmoplantar psoriasis. Methods Patients with non‐pustular palmoplantar psoriasis affecting at least 10% of their palms and soles and with a modified palmoplantar psoriasis area and severity index (m‐PPPASI) of at least eight were recruited. Patients were randomized (1:1) to receive infliximab 5 mg/kg or placebo at weeks 0, 2 and 6. Patients initially randomized to placebo received infliximab at weeks 14, 16 and 20 whereas patients randomized to infliximab received additional infliximab infusions every 8 weeks until week 22. Results Twenty four (24) patients were randomized in this study. At week 14, 33.3% and 66.7% of patients treated with infliximab achieved m‐PPPASI 75 and m‐PPPASI 50 respectively compared to 8.3% for both m‐PPPASI 75 (P = 0.317) and m‐PPPASI 50 (P = 0.009) for patients randomized to placebo. A reduction of 50.3% in the mean surface area of palms and soles affected with psoriasis was seen at week 14 in patients randomized to infliximab as compared to an increase of 14.9% in patients randomized to placebo (P = 0.009). Conclusions This pilot study did not reach its primary endpoint of m‐PPPASI 75 at week 14. However, infliximab was observed to be more efficacious than placebo in improving PPSA and with respect to the percentage of patients reaching m‐PPPASI 50 at week 14. Larger and longer term studies are needed for severe patients to better assess the efficacy of infliximab in palmoplantar psoriasis.     

Adalimumab administration after infliximab therapy is a successful treatment strategy for generalized pustular psoriasis

We report a case of a 70‐year‐old woman with generalized pustular psoriasis (GPP) who responded well to infliximab therapy and adalimumab therapy after secondary failure of infliximab therapy, but did not respond to ustekinumab therapy. We speculate that the pathogenic factor in this case favored anti‐tumor necrosis factor (TNF)‐α therapy to anti‐interleukin‐12/23 therapy. Herein, we also briefly present three additional cases of treatment with adalimumab after secondary failure of infliximab. GPP is often difficult to treat, and no placebo‐controlled trials have been conducted to guide the use of biologics against it because of a paucity of cases. Infliximab and adalimumab are anti‐TNF‐α antibodies that specifically block the interaction of TNF‐α with its receptors. Infliximab has been reported to be effective, with a rapid clearance of symptoms, even in cases of severe GPP. Adalimumab could be a good biologic candidate that can be administrated after secondary failure of infliximab therapy.     

Serum chemerin is increased in patients with chronic plaque psoriasis and normalizes following treatment with infliximab

Background Chronic plaque psoriasis is associated with obesity, which is a metabolic and inflammatory disorder. Adipokines are involved in the pathogenesis of psoriasis and they are biomarkers of obesity‐related inflammation. Objectives To measure serum adipokines in patients with chronic plaque psoriasis treated with infliximab. Methods Serum levels of chemerin, resistin, visfatin, C‐reactive protein (CRP), lipids, glycaemia and liver enzymes were measured in 40 patients with psoriasis and 40 controls matched by age, sex and body mass index (BMI). Adipokines were measured at baseline and after 2–12 months of treatment with infliximab 5 mg kg^?1. Results At baseline, levels of chemerin (195·9 ± 48·5 vs. 145·6 ± 27·1 ng mL^?1), resistin (2·03 ± 0·9 vs. 1·4 ± 0·5 ng mL^?1) and CRP (5·5 ± 7·3 vs. 1·9 ± 4·4 mg L^?1) were higher (P < 0·01) in patients with psoriasis compared with controls. Psoriasis was associated with elevated chemerin level independently of age, sex, BMI and levels of cholesterol and triglycerides. Chemerin was linearly correlated to CRP (r = 0·4, P = 0·01) and resistin (r = 0·3, P = 0·01). Chemerin levels were higher in patients affected by psoriatic arthritis than in patients with psoriasis without arthritis (195·5 ± 49·1 vs. 158·1 ± 37·5 ng mL^?1, P = 0·01). After 2 months of infliximab treatment a significant reduction of chemerin, resistin and CRP levels was observed. Conclusions Patients with psoriasis have higher blood levels of adipokines, which normalize during therapy with infliximab. Whether this reduction is a direct effect of infliximab or secondary to a reduction of inflammation should be further investigated.     

Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti‐TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 8.1; 95% CI: 4.2–15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6–16.3, p < .001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 2.3; 95% CI: 1.4–3.8, p = .01) or infliximab (OR: 2.2; 95% CI: 1.1–4.1, p = .018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti‐TNF agents for the treatment of PsO and PsA patients.     

Enhanced CCR9 expression levels in psoriatic skin are associated with poor clinical outcome to infliximab treatment

Infliximab is an anti‐tumor necrosis factor (TNF)‐α antibody drug that suppresses TNF‐α and its associated inflammatory responses. Although infliximab therapy generally results in a 75% or greater improvement in the Psoriasis Area and Severity Index from baseline in psoriasis patients, there is the heterogeneity of therapeutic efficacy in psoriasis patients among patients of a similar PASI baseline score. However, there are few published reports about the predictors of the clinical response among psoriasis patients who undergo biologic therapies. We thus evaluated the possible existence of biologic markers that would indicate poor prognosis of infliximab using skin biopsy specimens. This was because we assumed that the inhibitors for upregulated chemokine/chemokine receptors in non‐responders may have the ability to reduce the occurrence of psoriatic eruptions. PCR array analyses identified that the levels of various chemokines and chemokine receptors were increased in non‐responders in comparison to responders. Immunohistochemical analyses revealed that upregulation of the CCR9 protein levels was not associated with the pretherapeutic PASI score, but with poor response to infliximab. Our results indicated that the expression levels of CCR9 in lesional skin may be a useful biologic marker of the clinical efficacy of infliximab therapy in psoriasis patients.     

Body weight increment in patients treated with infliximab for plaque psoriasis

Background Psoriasis is frequently associated with overweight and obesity. Anti‐TNF‐α therapies are effective in the treatment of psoriasis. TNF‐α is highly involved in body weight regulation. Objective Our objective was to evaluate the increase in weight throughout the treatment with infliximab and the association of weight gain with the body mass index (BMI). Methods Thirty‐five patients affected with severe plaque psoriasis receiving infliximab were included. A control group consisted of 16 patients affected with severe plaque psoriasis and treated with cyclosporine, methotrexate, or acitretin. Assessment of PASI score, body weight and BMI were performed at a 1 and 3‐year follow‐up. Results We observed a body weight increment of 2.5 ± 4.4 kg (mean ± SD) (i.e. + 3.6% of baseline) and 0.1 ± 5 kg (i.e. + 1.2%) in patients treated with infliximab and the control group, respectively (P = 0.046), after 1 year of treatment. After 3 years of infliximab administration, weight gain was 4.8 ± 5 kg (n = 16) (i.e. + 6%) (P = 0.005). Moreover, as classified by BMI, normal weight patients experienced a 4 ± 3.7 kg weight gain (i.e. + 6%) whereas overweight and obese patients had gained 1.3 ± 4.8 kg (i.e. + 1.2%) (P = 0.039) after 1 year of anti‐TNF‐α therapy. Percentual changes in body weight were larger in normal weight patients at baseline than in overweight/obese counterparts (P = 0.0149). Conclusion All patients, including normal weight patients, should receive a dietary intervention.     

Infliximab for the treatment of psoriasis in Greece: 4 years of clinical experience at a single centre

Background Infliximab, a chimeric monoclonal antibody, has been shown to be effective for moderate to severe psoriasis. Clinical experience with long‐term infliximab therapy for psoriasis is accumulating, and it is therefore important to share our experience with its use in real‐life clinical practice. Objectives To report our experience with infliximab (Remicade^®; Schering Plough, Kenilworth, NJ, U.S.A.) for the treatment of moderate to severe plaque psoriasis (and/or arthritis) from a single clinic in Greece. Patients and methods Between August 2004 and March 2008, 62 patients presenting to our clinic with moderate to severe psoriasis were treated with infliximab. Disease phenotype, clinical course, disease severity and adverse events were assessed throughout the treatment period. Results Infliximab resulted in a reduction of median Psoriasis Area and Severity Index (PASI) of 70% at week 6 and 84·4% at week 14. Nineteen patients who have completed 1 year on infliximab treatment experienced sustained efficacy with a median PASI improvement of 92·16% and a Physician’s Global Assessment (PGA) of ‘clear’ or ‘almost clear’, while nine patients have reached approximately 20 months of continuous therapy. All patients with psoriatic arthritis showed marked improvement in their clinical symptoms following the first infusion. Eight patients (12·9%) experienced adverse events that required discontinuation of treatment. There were no statistically significant differences in PASI and Dermatology Life Quality Index (DLQI) scores between patients with arthritis and those with only skin lesions, or between those who received methotrexate, either from the beginning or during infliximab therapy, and those who did not receive methotrexate at all. Selected patients of interest are discussed. Conclusions The above data confirm previous reports that treatment with infliximab is an efficacious and safe option for patients with moderate to severe plaque psoriasis (and/or arthritis). Long‐term follow‐up, continued pharmacovigilance, and controlled comparative studies will be required to fully evaluate its use in the treatment of psoriasis.     

Efficacy and safety of biologics in erythrodermic psoriasis: a multicentre, retrospective study

Background Even though efficacy of biologics has been extensively studied in psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of the disease, have been scarcely reported. Objectives To address the efficacy and safety of biologics in patients with erythrodermic psoriasis. Methods A multicentre national retrospective study was performed using the French Psoriasis Group network. Patients showing psoriasis involving at least 90% of body surface area (BSA), and in whom severity of the disease had been evaluated before and after 3 and/or 6 months of treatment with biologics, were enrolled in the study. Results were expressed using intention‐to‐treat analysis. Results We included 28 patients, representing 42 flares of erythrodermic psoriasis treated with infliximab (n = 24), adalimumab (n = 7), etanercept (n = 6), ustekinumab (n = 3) or efalizumab (n = 2). A 75% improvement of BSA or Psoriais Area and Severity Index 12–14 weeks after treatment onset was reached in 48% of flares treated with infliximab, in 50% of those treated with adalimumab and in 40% of those treated with etanercept. Twelve serious adverse events, consisting of bacterial infection in seven of them, were observed. Biological treatment was discontinued for safety concern in 19% of cases. A given biologic was administered for up to 48 weeks in 34% of flares. Conclusions Biologics show overall good short‐term efficacy, but treatment switch due to lack of efficacy or side‐effects is frequently observed on a longer term, with only one‐third of patients still receiving the same drug after 1 year. The most significant safety concern consists of severe infections.     

Multidrug resistant miliary tuberculosis during infliximab therapy despite tuberculosis screening

We describe an unusual case of multidrug‐resistant miliary tuberculosis diagnosed 9 months after the commencement of infliximab treatment for psoriasis despite negative pretreatment tuberculosis screening, including chest X‐ray and interferon‐gamma release assay. After 4 months' treatment with amikacin, ethambutol, pyrazinamide and moxifloxacin, infliximab was restarted with concomitant anti‐TB medications. No recurrence of tuberculosis has been detected 12 months after recommencing infliximab.     

Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis

We examined the relation between adalimumab and infliximab plasma trough levels, anti‐adalimumab and anti‐infliximab antibody formation. We analyzed plasma from 32 adalimumab‐treated and 20 infliximab‐treated psoriasis patients for evaluating trough levels of each drug. The presence of anti‐adalimumab and anti‐infliximab antibodies was analyzed and the severity of psoriasis was evaluated. At week 28, 25 out of 32 and at week 48, 21 out of 30 adalimumab‐treated patients maintained as more than PASI 75. At week 28, 12 out of 20 and at week 48, nine out of 18 infliximab‐treated patients were evaluated as more than PASI 75. In patients treated with 40 mg adalimumab every other week, the mean trough level was 7.62 μg/mL (range, 0.05–10.6) at week 48. In patients treated with 80 mg adalimumab every other week, the mean trough level was 8.61 μg/mL (range, 0.08–13.5) at week 48. Mean trough level of infliximab‐treated cases (4.1–5.2 mg/kg; mean, 4.6) was 4.64 μg/mL (range, 0.03–16.9) at week 48. Anti‐adalimumab antibody was detected in five out of 32 cases and anti‐infliximab antibody was detected in six out of 20 cases, respectively, at weeks 24 and 48. The optimal cut‐off values of adalimumab and infliximab concentration for more than PASI 75 were more than 7.84 μg/mL and more than 0.92 μg/mL, respectively. The trough levels of adalimumab and infliximab in psoriasis patients were positively associated with clinical response and were significantly lower in cases having anti‐adalimumab or anti‐infliximab antibodies.