Evaluating the use of the interferon‐γ response to Mycobacterium tuberculosis‐specific antigens in patients with psoriasis prior to antitumour necrosis factor‐α therapy: a prospective head‐to‐head cross‐sectional study

Background Targeted biological therapies have transformed the treatment of chronic inflammatory disease. However, reactivation of latent tuberculosis infection (LTBI) is a significant risk with the use of antitumour necrosis factor (anti‐TNF)‐α therapy and screening is mandatory prior to treatment. The tuberculin skin test (TST) may be difficult to interpret in patients with inflammatory disease or receiving immunosuppressive therapies. Objectives The aim of this study was to evaluate and compare the QuantiFERON^®‐TB Gold In‐Tube (QFR) and T‐SPOT.TB (TSTB) interferon‐γ‐release assays (IGRA) against the TST in a cohort of patients commencing anti‐TNF‐α therapies for chronic inflammatory disease. Methods A prospective cross‐sectional study was undertaken at a London tertiary referral centre. Demographic data collected included TB risk factors. TST, QFR and TSTB were performed in all patients. Results Seventy patients with chronic plaque psoriasis were included in the study. Agreement between QFR and TSTB, excluding indeterminate results, was 89% (κ = 0·567), between QFR and TST 85% (κ = 0·313) and 81% (κ = 0·244) between TSTB and TST. There was no significant association with concomitant immunosuppression and either TST or IGRA results. Seven patients received chemoprophylaxis for LTBI diagnosed after clinical risk assessment together with positive TST and/or IGRA. Three patients had positive results in all three tests. Conclusions While there was moderate overall agreement between QFR and TSTB and fair correlation between TST, QFR and TSTB, there were a number of discordant results, suggesting that a three‐pronged approach using TST, QFR and TSTB may be of additional benefit.     

Clinical applicability of Quantiferon-TB-Gold testing in psoriasis patients during long-term anti-TNF-alpha treatment: a prospective, observational study

Background Psoriasis patients who are treated with tumour necrosis factor (TNF)‐alpha antagonists are at increased risk of reactivation of latent tuberculosis infection (LTBI) and should be adequately screened and monitored during active treatment. Objectives To evaluate in a prospective study, the performance of Quantiferon‐TB‐Gold in tube (QFT) in vitro assay compared to the conventional tuberculin skin test (TST) in detecting LTBI among a cohort of non‐BCG‐vaccinated patients with moderate‐to‐severe psoriasis during long‐term treatment (12 months) with TNF‐alpha antagonists. Methods A total of 50 patients underwent QFT and TST testing at baseline and after 6 and 12 months of continuous anti‐TNF‐alpha treatment. Diagnosis of LTBI was made on the basis of a positive QFT result and negative chest‐radiographic and microbiological assays. Patients with LTBI were subjected to standard isoniazid chemoprophylaxis and after 1 month, they resumed anti‐TNF‐alpha treatment with subsequent QFT and TST testing after 6 months. In all the cases, a follow‐up period of 12 months was observed. Results During the 12‐month‐study period, 14% of patients presented a QFT conversion. During active anti‐TNF‐alpha treatment, a QFT conversion was observed in 10% of patients (five cases). Agreement between QFT and TST was moderate (κ = 0.408) at screening, good (κ = 0.734) after 6 months and fair (κ = 0.328) after 12 months of treatment. A total of 18% of patients presented a positive, discordant TST during the study period. Conclusions A single‐test QFT‐based screening strategy for LTBI in psoriasis patients receiving long‐term anti‐TNF‐alpha treatment could reduce the incidence of false‐positive LTBI cases, preventing unnecessary TB chemoprophylaxis.     

Incidence of tuberculosis infection in psoriatic patients on anti‐TNF therapy: report of a case series with 144 patients

Background Worldwide clinical trials and post‐marketing surveillance data have demonstrated an increased incidence of tuberculosis (TB) disease associated with antitumour necrosis factor (anti‐TNF) agents. The majority of these cases are presumed to result from a reactivation of latent disease, while the rate of new infections is unknown. A study was performed to evaluate the incidence of latent tuberculosis infection (LTBI) in psoriatic patients screened for biological therapy in a high‐incidence area, such as Madrid, Spain. Patients and methods One hundred and forty‐four patients with moderate‐to‐severe psoriasis treated with anti‐TNF agents were recruited. All of them were screened for active TB or LTBI before therapy. The screening included a detailed medical study, physical examination, chest X‐ray, tuberculin skin test (TST) with purified protein derivative and re‐TST. Results A total of 42 (29%) patients were diagnosed with LTBI based on a positive TST or re‐TST, and/or signs of past TB in the chest X‐ray. All of them received chemoprophylaxis with isoniazide. One patient developed a primary active lymphnode TB. Conclusion This is the first study to underscore the incidence of LTBI in patients with psoriasis treated with anti‐TNF therapy in the Spanish population. We support that the use of TST is still reliable and an effective diagnostic method for the detection of LTBI in anti‐TNF therapy.     

Management of long‐term therapy with biological drugs in psoriatic patients with latent tuberculosis infection in real life setting

Psoriatic patients with latent tuberculosis infection (LTBI) need a prophylaxis before starting a treatment with biological drugs. The aim of this study is to investigate the safety and efficacy of prophylaxis of LTBI in psoriatic patients receiving long‐term biological drugs. The study included 56 patients (42 male and 14 female) affected by moderate‐to‐severe psoriasis (mean PASI: 12.8 ± 6.9 SD) treated with anti‐TNF‐α and/or anti IL 12, 23 and/or anti‐CD11 drugs with a diagnosis of LTBI. LTBI diagnosis was based on tuberculin skin test and/or QuantiFERON TB Gold test positivity and chest X‐ray suggestive, without clinical, or microbiological evidence of active disease. All patients received prophylactic therapy for 9 months with isoniazid (INH) 300 mg/day, starting 3 weeks before the beginning of biological treatment. Fifty‐four patients completed prophylaxis with INH without any adverse events or intolerance; they continue the biological treatment without appearance of active tuberculosis. One patient developed tuberculosis pleurisy in course of treatment with etanercept. The infection has been treated and after a stable remission, treatment was restarted without tuberculosis reactivation. In this retrospective analysis, the prophylaxis of LTBI whit INH was effective and safe in longer follow‐up period.     

Clinical experience of QuantiFERON(®) -TB Gold testing in patients with psoriasis treated with tumour necrosis factor blockers in Taiwan

Background In Taiwan, an intermediate tuberculosis burden country, around 9·3% of patients with rheumatoid arthritis treated with adalimumab develop tuberculosis despite prescreening with the tuberculin skin test. Within the Asia‐Pacific region, the tuberculosis risk in patients with psoriasis who use tumour necrosis factor (TNF) blockers is unknown. Objectives This study reports the use of QuantiFERON^®‐TB Gold (QFT‐G) (Cellestis, Melbourne, Vic., Australia) as a screening method for latent tuberculosis infection (LTBI) in patients with psoriasis. Methods This retrospective review evaluated 216 patients with psoriasis in whom TNF blockers were considered between 2004 and 2009 in a tertiary referral hospital in Taiwan. Beginning in 2007, QFT‐G was performed on all patients who were candidates for TNF blockers. Results Seventeen patients who used TNF blockers for less than 4 weeks were excluded. Of the 147 assessed patients receiving TNF blockers, 110 (75%) underwent QFT‐G tests. A total of 126 (86%) patients used etanercept and 40 (27%) patients used adalimumab. Nineteen patients switched between both. Overall, patients had a median of 24 weeks (range 4–307) exposure to TNF blockers. Twelve patients (11%) who were treated with TNF blockers and eight (15%) without TNF blockers had positive QFT‐G results. Of all TNF blocker users, only one patient (0·68%) developed tuberculosis. Conclusions QFT‐G can be used to screen for LTBI in a tuberculosis endemic area where bacille Calmette–Guérin vaccination coverage is high. Isoniazid prophylaxis is recommended for those who have positive QFT‐G test results.     

Sequential Stevens-Johnson syndrome and photo-recall phenomenon

Summary Background Ustekinumab is a monoclonal antibody that targets interleukin (IL)‐12/23 p40 to treat psoriasis. The IL‐12 pathway is also important in regulating immunity to Mycobacterium tuberculosis. Objectives To evaluate the safety of isoniazid (INH) prophylaxis for newly identified latent tuberculosis infection (LTBI) in ustekinumab‐treated patients with psoriasis. Methods Safety data from 3177 psoriasis patients evaluated across five phase III trials of ustekinumab (45 or 90 mg) conducted in North America, Europe and Asia were analysed. LTBI was diagnosed based on positive tuberculin skin test or QuantiFERON^®‐TB test (Cellestis, Carnegie, Vic., Australia) without evidence of active tuberculosis. Results At baseline, 101/2898 (3·5%) non‐Asian and 66/279 (23·7%) Asian patients were newly identified with LTBI, and all were treated with INH. Through week 12, among patients who received INH, rates of adverse events (AEs) representative of INH toxicity were generally comparable between control and ustekinumab‐treated patients, as well as between ustekinumab dose groups. Markedly abnormal alanine transaminase values occurred with comparable incidences between control and ustekinumab‐treated patients. The rate of study agent discontinuation due to INH toxicity was low (5/167, 3·0%) and comparable between control and ustekinumab groups through week 12. The rate of INH‐related AEs did not increase disproportionately through week 28. No cases of active tuberculosis were reported in patients who received concomitant INH starting at baseline. Conclusions Across five trials of ustekinumab‐treated patients with psoriasis, no cases of LTBI reactivation were observed in patients receiving concomitant INH prophylaxis for LTBI. INH prophylaxis was generally well tolerated by these patients with psoriasis.     

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.     

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.     

Markers of systemic inflammation in psoriasis: a systematic review and meta‐analysis

Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)‐1β, IL‐6, IL‐10, C‐reactive protein (CRP), intracellular adhesion molecule (ICAM)‐1, E‐selectin and tumour necrosis factor (TNF)‐α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random‐effects model. Seventy‐eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL‐6 [d = 1·32, 95% confidence interval (CI) 0·83–1·81], CRP (d = 1·83, 95% CI 0·76–2·90), TNF‐α (d = 1·32, 95% CI 0·86–1·79), E‐selectin (d = 1·78, 95% CI 1·32–2·25) and ICAM‐1 (d = 1·77, 95% CI 1·15–2·39). The SMD between cases and controls for IL‐1β and IL‐10 was not significant. Age had a significant effect on the SMD for IL‐6 and TNF‐α. For IL‐6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy.     

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.     

Efficacy comparison of ustekinumab between anti‐tumor necrosis factor‐α drug‐naïve and anti‐tumor necrosis factor‐α drug‐resistant Japanese psoriasis cases

Ustekinumab is highly efficacious for psoriasis; however, it has not been fully clarified whether previous failure in anti‐tumor necrosis factor‐α (TNF‐α) therapy affects the treatment response with ustekinumab. Therefore, we evaluated the efficacy of ustekinumab in anti‐TNF‐α‐naïve and anti‐TNF‐α‐resistant cases and compared the clinical efficacies of adalimumab and ustekinumab in biologic naïve cases. Thirty‐five patients with plaque psoriasis who showed resistance to conventional therapies were enrolled; 26 patients, who had never been treated with biologics, were allocated to ustekinumab or adalimumab; nine patients who failed to achieve psoriasis area and severity index (PASI) 50 at week 16 with one or two TNF‐α antagonists were switched to ustekinumab. The end of the study was defined as 52 weeks after starting the first biologic for anti‐TNF‐α‐naïve patients and after switching to ustekinumab for anti‐TNF‐α‐resistant patients. The primary outcome measurement was the percentage of patients achieving PASI75 at week 16. In patients treated with ustekinumab, 87.5% of anti‐TNF‐α‐naïve and 77.8% of anti‐TNF‐α‐resistant cases achieved a PASI75 response at week 16, and no statistically significant difference was found between the treatment response rates (P = 0.60). When comparing the treatment efficacy of ustekinumab and adalimumab among anti‐TNF‐α‐naïve patients, there was also no statistically significant difference in PASI75 achievement rates (87.5 vs. 83.3%, P = 0.79). Our study suggests that ustekinumab can be considered as a first‐line biologic for psoriasis and a rescue therapy for anti‐TNF‐α‐resistant cases.     

Efficacy and safety of adalimumab in patients with psoriasis previously treated with anti‐tumour necrosis factor agents: subanalysis of BELIEVE

Background Few large clinical studies have evaluated whether switching tumour necrosis factor antagonists (anti‐TNFs) is likely to improve psoriasis in patients with prior anti‐TNF treatment. Objective The aim of this subanalysis of the BELIEVE study was to assess the efficacy and safety of adalimumab for psoriasis in patients with and without previous anti‐TNF treatment. Methods The BELIEVE study enrolled patients with moderate to severe psoriasis and prior failure, intolerance or contraindication to ≥2 systemic therapies. In this 16‐week, double‐blind, randomized, controlled trial, patients received adalimumab (80 mg, week 0; 40 mg every other week, weeks 1–15) with either topical vehicle or topical calcipotriol/betamethasone dipropionate (C/B) applied once daily for 4 weeks, then as needed. The primary endpoint was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. This post hoc subanalysis evaluated the safety and efficacy of adalimumab, with and without topical therapy, in BELIEVE patients who had prior exposure to anti‐TNFs. Results Of 730 patients enrolled, 282 (38.6%) had prior anti‐TNFs and 448 (61.4%) were anti‐TNF‐naïve. Combining topical vehicle and topical C/B study populations, 61.7% of patients with prior anti‐TNFs achieved PASI 75 at week 16, compared with 71.7% of anti‐TNF‐naïve patients (P = 0.095). Adalimumab resulted in clinically meaningful improvement regardless of which prior anti‐TNF agent had been used, the number of prior anti‐TNFs tried, or reasons for discontinuation of prior anti‐TNF therapy. Adverse event incidences were similar between patients with and without prior anti‐TNF therapy. Conclusion Adalimumab was effective and well‐tolerated in patients with psoriasis previously treated with anti‐TNF therapy.     

Effects of anti‐TNF‐α agents on circulating endothelial‐derived and platelet‐derived microparticles in psoriasis

Psoriasis involves TNF‐α secretion leading to release of microparticles into the bloodstream. We investigated the effect of TNF blockers on microparticles levels before and after treatment in patients (twenty treated by anti‐TNF‐α agents and 6 by methotrexate) with severe psoriasis. Plasmatic microparticles were labelled using fluorescent monoclonal antibodies and were analysed using cytometry. Three months later, 70% of patients treated with anti‐TNF‐α agents achieved a reduction in PASI score of at least 75%. The clinical improvement in patients treated with anti‐TNF‐α agents was associated with a significant reduction of the mean number of platelet microparticles (2837/μl vs 1849/μl, P = 0.02) and of endothelial microparticles (64/μl vs 22/μl, P = 0.001). Microparticles are significantly decreased in psoriatic patients successfully treated by anti‐TNF‐α. Microparticles levels as circulating endothelial cells represent signs of endothelial dysfunction and are elevated in psoriasis. Then, TNF blockade may be effective to reduce cardiovascular risk through the reduction of circulating microparticles.     

Prevalence of metabolic syndrome in children with moderate to severe psoriasis treated with TNF inhibitors in comparison to conventional agents

Association of childhood psoriasis with metabolic syndrome has not been studied well. TNF‐alfa contributes to the inflammation seen in metabolic syndrome, and recently etanercept has shown to reduce the levels of inflammatory markers. Assessment of prevalence of metabolic syndrome in juvenile psoriasis patients in Kuwait. We included 236 patients with moderate to severe psoriasis below 18 years treated for at least 24 weeks with TNF inhibitors (Group A), and equal number of age and sex matched cases treated with conventional medications (Group B). The metabolic syndrome (MBS) was defined according to the International Diabetes Foundation (IDF 2007 criteria for children). Increased waist circumference was seen in 56.77% of cases in Group A. Triglyceridemia was less frequent in Group A. MBS was higher in Group B [41·52% vs. 50·42%, odds ratio (OR) 1·76, 95% CI 1.19–2.41; p = .005]. Psoriasis is associated with higher prevalence of metabolic syndrome in children. Six months of anti TNF treatment showed lesser association with metabolic syndrome. With fasting blood glucose, and serum TG seen in significantly lesser number of patients in this group.     

Latent tuberculosis infection and active tuberculosis in patients with psoriasis: a study on the incidence of tuberculosis and the prevalence of latent tuberculosis disease in patients with moderate–severe psoriasis in Spain. BIOBADADERM registry

Introduction The incidence of tuberculosis (TB) or the prevalence of latent tuberculosis infection (LTBI) in psoriasis patients has not been described in the Spanish population. We carried out a study with the objectives: (i) To describe the incidence of TB in patients with psoriasis on systemic treatment in the Spanish population; (ii) To determine the prevalence of LTBI in patients who are candidates for biological treatment; and (iii) To investigate the level of compliance with current recommendations for LTBI and TB screening. Methods Data were obtained from BIOBADADERM (Spanish registry for systemic biological and non‐biological treatments in psoriasis). An analysis was performed of the exposed cohort to determine the prevalence of LTBI and to describe compliance with the screening guidelines. Results A total of 1425 patients were registered in BIOBADADERM. They included 793 (56%) patients exposed to biological treatment and 632 (44%) treated with conventional systemic drug. Overall follow‐up was 3720 person‐years. Of the 793, 20.5% (163) were diagnosed with LTBI before starting biological treatment. The rate of active TB for the exposed cohort was 145 cases × 100 000 patient‐years (95% CI 54–389). No case of TB was found in the control group. Screening for LTBI was performed in 83% of the exposed sample. Conclusion Patients with psoriasis who are exposed to biological treatment appear to be at greater risk for tuberculosis. In Spain, up to 20% of patients with psoriasis who are candidates for biological therapy have LTBI. There continues to be a significant percentage of errors in compliance with clinical guidelines.     

The reliability of tuberculin skin test in the diagnosis of latent tuberculosis infection in psoriasis patients: A case‐control study

Tuberculin skin test (TST), which is used in the diagnosis of latent tuberculosis infection, may cause Koebner's phenomenon and false‐positive results in psoriasis patients. The purpose of this study is to compare TST with QuantiFERON‐TB Gold Plus (QFT‐plus) test in psoriasis patients and to determine the effects of psoriasis on TST results. Ninety‐two psoriasis patients and 30 control subjects were included in the study. QFT‐plus test, TST, and prick test to distinguish the increase of induration because of the skin trauma were performed on both groups. The demographics, risk factors for latent tuberculosis infection, BCG vaccination history, Koebner's history, psoriasis severity, and treatment history of the patients were recorded. The effects of these variables on test results were investigated by comparing those with control group. The criteria of National Tuberculosis Diagnosis and Treatment Guidelines were used in the evaluation of test results, and threshold value of positivity for TST was taken as 10 mm in BCG‐vaccinated patients who are planned to start biological treatment. Prick test results were negative in the control group. There was no significant relation between the results of prick test and TST induration diameters in the patient group. Although TST positivity was significantly higher in patients (62%) compared with control group (33%), QFT‐plus test results were not statistically different between two groups. Agreement between two tests was determined to be low in patient group with 48% (K = 0.1), and it was determined to be moderate with 77% in control group (K = 0.4). QFT‐plus test was found to be negative in 46 of 57 TST‐positive patients (80.7%) in patient group. It was determined in both groups that vaccination did not have any effect on test results. When threshold value was lowered to 5 mm in patient group without considering BCG reaction, the number of TST‐positive patients increased from 57 to 65. Mean TST induration diameter was 10 mm and 14 mm in cases with mild and moderate to severe clinical manifestation, respectively (P = .04). However, no effect of disease period and treatment was determined on both test results. TST positivity was higher in psoriasis patients compared with control group. It was considered due to the increased reaction of the skin to mycobacterial antigens rather than the Koebner's response. Although TST results were not affected by BCG, it was concluded that a 10‐mm threshold value of positivity was a suitable approach in order to reduce the number of patients receiving unnecessary preventive treatment in patients who are considered to initiate biologic agents. Furthermore, it was also concluded that QFT‐plus test may be preferred in psoriasis patients since it is applied in vitro and its specificity is higher and not affected by disease severity.     

Responses to ustekinumab in the anti‐TNF agent‐naïve vs. anti‐TNF agent‐exposed patients with psoriasis vulgaris

Background Approximately 20–30% of patients with psoriasis treated with anti‐tumour necrosis factor α (TNFα) agents will discontinue treatment within 2 years due to loss of efficacy or side‐effects. Switching to another anti‐TNFα agent produces clinical responses inferior to previously untreated patients. Ustekinumab binds to the p40 subunit of interleukin (IL)‐12 and IL‐23 and provides a mechanism of action independent of TNFα. Objective To investigate the efficacy of ustekinumab in a clinical practice setting and to compare treatment responses to ustekinumab in patients previously treated with TNFα inhibitors and anti‐TNFα‐naïve patients. Methods Patients receiving either ustekinumab (n = 71) or the subcutaneous TNFα inhibitors adalimumab or etanercept (n = 108) were identified through the registry of psoriasis patients in our Institutions. Efficacy effect outcome was a 75% improvement in the psoriasis area severity index (PASI75). Kaplan–Meier statistics evaluated the adherence to the treatments expressed as drug survival rate. Results PASI75 was achieved in 80% of the ustekinumab‐treated patients after a median time of 112 days. There was no difference in efficacy in anti‐TNFα‐naïve patients compared with anti‐TNFα unresponsive patients. Patients treated with ustekinumab showed a superior adherence to treatment in comparison with adalimumab and etanercept. Limitations Patients were non‐randomly assigned to treatment, which potentially may lead to biases. Observation time was short (1 year). Conclusion In clinical practice, the short‐term efficacy and patient adherence to ustekinumab are excellent and comparable to the data obtained in clinical trials. Lack of response to previous anti‐TNF treatment does not impair clinical response to ustekinumab.     

Screening for latent tuberculosis infection in psoriasis and psoriatic arthritis patients in a tuberculosis‐endemic country: a comparison of the QuantiFERON®‐TB Gold In‐Tube test and tuberculin skin test

Since the introduction of biologic therapies for tuberculosis (TB), screening for latent TB infection has increased in importance, especially in countries in which TB is endemic. The aim of this study was to evaluate the effect of psoriasis on tuberculin skin test (TST) results and to compare two TB screening tests, the TST and QuantiFERON^®‐TB Gold In‐Tube (QFT–GIT) test, in psoriasis and psoriatic arthritis (PA) patients living in a TB‐endemic country (Turkey). This prospective study included 61 psoriasis and 40 PA patients, and 58 healthy controls. Demographic data, medical history, human immunodeficiency virus (HIV) status, level of education, smoking status, exposure to TB, personal and family histories of TB, and bacillus Calmette–Guérin (BCG) vaccination status were recorded for all participants. The TST and QFT–GIT were performed in all participants. The mean ± standard deviation TST indurations in the patient and control groups were 12.6 ± 6.4 mm and 10.2 ± 6.5 mm, respectively (P = 0.051). The TST positivity rate was higher in patients than in controls (86.1% vs. 37.9%; P < 0.001), whereas QFT–GIT positivity did not differ significantly (patients: 20.8%; controls: 17.2%; P = 0.737). False positive results can lead to unnecessary prophylactic TB treatment; therefore, the cut‐off point for TST positivity in psoriasis and PA patients should be re‐evaluated, or other tests, such as the QFT–GIT, should be used.     

Candida infections in patients with psoriasis and psoriatic arthritis treated with interleukin‐17 inhibitors and their practical management

The recognition of the central role of interleukin (IL)‐17A in the pathogenesis of psoriasis has led to the development of several monoclonal antibodies targeting this cytokine or its receptors for therapeutic purposes. IL‐17A also plays an important role in immunological protection against infections, especially those due to Candida spp., as evidenced by findings in patients with genetic defects in IL‐17‐related immune responses. To assess the potential of anti‐IL‐17 treatment to promote Candida infections, here we have systematically reviewed published clinical trials of patients with psoriasis or psoriatic arthritis. Candida infections were reported in 4·0% of patients treated with brodalumab, 1·7% with secukinumab and 3·3% with ixekizumab vs. 0·3%, 2·3% and 0·8% of those assigned to placebo, ustekinumab or etanercept, respectively. Although the incidence of Candida infection was found to be increased by only a small degree during anti‐IL‐17 therapy, patients undergoing such treatment should be monitored for fungal infection and treated as necessary. We propose adoption of the recently updated recommendations for the practical management of Candida infection in patients administered IL‐17 inhibitors.     

TNF-alpha gene 1031 T/C polymorphism in Turkish patients with Behçet's disease

Background Genetic factors that predispose individuals to Behçet's disease (BD) are considered to play an important role in development of the disease. The tumour necrosis factor (TNF)‐α gene, which is closely linked to the HLA‐B51 gene, is involved in susceptibility for BD. Recently, a polymorphism at position ?1031 within the TNF‐α promoter region was demonstrated to be responsible for susceptibility to BD in a British population. However, the functional effects of this polymorphism have not yet been determined. Objectives To investigate the possible relation of the TNF‐α–1031 T/C polymorphism with susceptibility to BD in a Turkish population and to determine the functional importance of this polymorphism. Methods Ninety‐nine unrelated patients (47 women, 52 men; mean ± SD age, 34·10 ± 10·53 years) with BD and 103 ethnically matched healthy controls (52 males, 51 females; mean ± SD age, 40·25 ± 14·15) were enrolled in the study. For genotyping, polymerase chain reaction – restriction fragment length polymorphism (PCR‐RFLP) analysis was employed. The functional importance of TNF‐α–1031 T/C polymorphism was determined with an enzyme‐linked immunospot (ELISPOT) assay. For this purpose, mononuclear cells obtained from BD patients and controls were analysed for TNF‐α and interferon (IFN)‐γ production. Results A significant difference was observed between BD patients and controls with respect to the allele frequency of TNF‐α–1031C [P = 0·018, OR = 1·83, 95% confidence interval (CI) = 1·07–3·13]. When the allele frequencies were analysed according to the clinical features, the T allele in patients with positive skin pathergy test (SPT) was significantly increased when compared with those of patients without these findings (P = 0·004, OR = 2·75, 95% CI = 1·3–5·86). To demonstrate the frequency of TNF‐α and IFN‐γ producing cells, mononuclear cells from four representative individuals of each genotype were used and the spontaneous and stimulated TNF‐α and IFN‐γ values (spot numbers) were analysed. Compared with the control groups, a significant increase was observed in the number of cells producing TNF‐α obtained from BD patients (P < 0·001). Moreover, the stimulation index for TNF‐α [bacterial lipopolysaccharide (LPS) stimulated/unstimulated] was higher for the CC genotype (9 ± 9·5) with respect to the other genotypes (TT; 1·3 ± 0·3 and TC; 1·2 ± 0·2). While the difference in the spontaneous IFN‐γ values between groups were not statistically significant, the stimulated IFN‐γ values were found to be significantly increased in the BD group when compared with the healthy control group (P = 0·004). Conclusions Our results showed that, in the Turkish population the TNF‐α–1031C allele is associated with susceptibility to BD. On the other hand, carrying the T allele may render patients more prone to developing a positive skin pathergy test. In addition, ELISPOT assays revealed that BD patients exhibited a significantly higher number of mononuclear cells producing TNF‐α, and cells obtained from patients with a CC genotype had a stronger response to LPS stimulation. The strong IFN‐γ response upon LPS stimulation in BD patients supports the previous findings that BD is a Th1 driven disease. These findings suggest that the TNF‐α–1031 polymorphism may have a functional effect and could explain the reason for high levels of TNF‐α production observed in BD patients.