Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-γ release assay vs. tuberculin skin test

Background Antitumour necrosis factor (anti‐TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon‐γ release assays (IGRA) have been shown to be more sensitive and specific than TST. Objective To compare the TST and the T‐SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti‐TNF treatment. Methods A retrospective study was carried out over a 4‐year period on patients with psoriasis requiring anti‐TNF treatment. All were subjected to the TST, T‐SPOT.TB and chest X‐ray. Risk factors for LTBI and history of bacillus Calmette–Guérin (BCG) vaccination were recorded. The association of T‐SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti‐TNF therapy when indicated. Results Fifty patients were included; 90% had prior BCG vaccination. A positive T‐SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7·43; 95% confidence interval 1·38–39·9), which was not the case for the TST. Agreement between the T‐SPOT.TB and TST was poor, κ = 0·33 (SD 0·13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T‐SPOT.TB. All patients received an anti‐TNF agent for a median of 56 weeks (range 20–188); among patients with a positive TST/negative T‐SPOT.TB, no tuberculosis was detected with a median follow‐up of 64 weeks (44–188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. Conclusion This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti‐TNF therapy, even if LTBI is correctly diagnosed and treated.     

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.     

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.     

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.     

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.     

Serial Quantiferon‐TB Gold test results in 279 patients with psoriasis receiving biologic therapy

The risk of active tuberculosis is still a concern in patients receiving biologics. To determine the risk of latent tuberculosis infection (LTBI) reactivation by Quantiferon‐TB Gold (QFT) assay in psoriatic patients treated with biologics in 11 years' follow‐up, along with chest radiography alterations. This retrospective study included 279 patients with plaque‐type and/or pustular, or nail psoriasis who were treated with biologics, and had results for ≥2 LTBI tests. The QFT outcomes were defined according to the baseline and the follow‐up QFT results; seroconversion as from negative to positive, seroreversion as from positive to negative, persistently seronegative as invariantly negative, persistently seropositive as invariantly positive, and other any result was accepted as indeterminate. Demographic features, the presence and the type of any chest X‐ray abnormality was noted during the follow‐up. Of 279 baseline QFT tests, the vast majority were negative (n = 193; 69%), with a less of positive (n = 86; 31%). Ten (5.2%) of 193 patients converted from negative to positive QFT status after starting biologic therapy (P < 0.001) during 11 years' follow‐up. Although these 10 patients exhibited seroconversion of QFT from negative to positive, only one patient was diagnosed with active TB. There was no statistically significant difference among biologics as regards with QFT seroconversion risk (P = .09). This study showed that 5.2% of patients showed seroconversion. Annual QFT testing remains a necessary and mandatory tool to prevent further TB reactivation in psoriasis patients taking biologic therapy although only one patient was diagnosed with active TB in this cohort.     

Unusual presentation of tuberculosis in an infliximab-treated patient – which is the correct TB screening before starting a biologic?

Infliximab is an anti-TNFα chimeric monoclonal antibody, commonly used in the treatment of moderate to severe psoriasis. TNFα is a pro-inflammatory cytokine which play a key role in host defense from infections by intracellular bacteria, such as Listeria monocytogenes , Histoplasma Capsulatum and especially Mycobacterium Tuberculosis . Infliximab therapy increases the risk of tuberculosis due mainly to the reactivation of latent TB infection (LTBI) and, therefore, it is mandatory to screen patients for LTBI prior to starting a treatment with anti-TNFα agents. We report the case of a psoriatic patient, who, despite a negative screening for infection by M. tuberculosis including both tuberculin skin test (TST) and chest X-ray, developed after 4 months of infliximab treatment, a severe pulmonary, lymphnodal and intestinal tuberculosis during infliximab treatment.     

Clinical applicability of T‐cell interferon‐α release assay for tumour necrosis factor‐α inhibitor therapy in severe psoriasis

Many studies have found that screening and treatment of latent tuberculosis (TB) before starting treatment with tumour necrosis factor (TNF)‐α inhibitors reduces associated TB infections. The new T‐cell interferon‐α release assay (TIGRA), is more specific and sensitive for detection of latent TB compared with the tuberculin skin test (TST). We report results of TIGRA in our first 63 patients commencing TNF‐α inhibitors for severe psoriasis. Of the 63 patients, 5 (7.9%) had a positive TIGRA result and were started on treatment for latent TB. We found that the only risk factor for TB associated with a positive TIGRA was a history of travel to countries with high TB incidence. To our knowledge, this is the first study to identify the background risk (7.9%) of latent TB in an endemic UK population. This result emphasizes the importance of TIGRA testing to reduce the risk of TB in patients treated with TNF‐α inhibitor.     

Risk of tuberculosis reactivation during interleukin-17 inhibitor therapy for psoriasis: a systematic review

Immunosuppressive therapies, effective in treating inflammatory disorders such as psoriasis, increase the risk of serious infections, such as tuberculosis (TB). For example, tumour necrosis factor (TNF)-alpha inhibitors significantly increase the risk of TB reactivation in patients with latent TB infection (LTBI), which has led clinicians to routinely test for TB prior to initiation of these medications. This protocol has since extended to other, newer immunomodulatory therapies for psoriasis, such as interleukin (IL)-17 inhibitors, including secukinumab, ixekizumab and brodalumab. We conducted a systematic review to examine whether there is any evidence that IL-17 inhibitor therapy for psoriasis increases the risk of TB reactivation. Using PubMed and EMBASE, our literature search resulted in 139 total articles. After manually reviewing each article for the discussion of IL-17 inhibitors for psoriasis, with data originating from clinical trials, and assessment for incidence of TB reactivation, 23 articles met the full inclusion criteria for our review. Overall, we found no cases of TB reactivation in patients treated with IL-17 inhibitors for psoriasis. This suggests that IL-17 inhibitors may be safely used in psoriasis patients with LTBI who receive appropriate LTBI treatment. However, long-term real-world studies are warranted to further evaluate this risk.     

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.     

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.     

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.     

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.     

Patients with psoriasis are more likely to be treated for latent tuberculosis infection prior to biologics than patients with inflammatory bowel disease

Screening for latent tuberculosis infection (LTBI) is recommended before treatment with biologics is initiated in patients with psoriasis or inflammatory bowel disease (IBD). Our objective was to evaluate the effect of underlying disease (psoriasis or IBD) on the risk of LTBI diagnosis prior to anti-tumor necrosis factor-alpha (TNF-α) therapy. During a two-year period LTBI diagnosis rate was compared in consecutive patients with psoriasis or IBD (Crohn's disease or ulcerative colitis). IBD patients (n = 33) had significantly smaller tuberculin skin testing compared to psoriasis patients (n = 30) (p = 0.007). Applying LTBI diagnosis guidelines resulted in more psoriasis (50%) than IBD patients (24.2%) receiving treatment for LTBI prior to onset of anti-TNF-α treatment (p = 0.04). In conclusion, current recommendations for LTBI diagnosis must be re-evaluated to account for the unique tuberculin hyperactive state of the skin of patients with psoriasis.     

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.     

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.     

Latent tuberculosis: Risk factors,screening and treatment in liver transplantation recipients from an endemic area

BACKGROUNDPatients undergoing solid organ transplantation, particularly those who live or have lived in tuberculosis (TB) endemic areas, are at a high risk of developing TB. The majority of post-transplantation TB cases are associated with reactivation of latent TB infection (LTBI). Brazil is in a single position with overlapping areas of high TB endemicity and high transplant activity. In liver transplant (LT), one should be aware of the potential hepatotoxicity associated with the treatment regimens for LTBI. AIMTo evaluate the frequency of LTBI in LT patients and treatment-related issues. METHODSThis was a retrospective analysis of a cohort of cirrhotic patients aged ≥ 18 years, who underwent LT at a high-complexity teaching hospital from January 2005 to December 2012.RESULTSOverall, 429 patients underwent LT during the study period. Of these, 213 (49.7%) underwent the tuberculin skin test (TST) during the pre-transplant period, and 35 (16.4%) of them had a positive result. The treatment for LTBI was initiated after LT in 12 (34.3%) of the TST-positive patients; in 3 (25.0%), treatment was maintained for at least 6 mo. CONCLUSIONThe prevalence of LTBI was lower than expected. Initiation and completion of LTBI treatment was limited by difficulties in the management of these special patients.     

Is tuberculin skin testing reliable during anti-tumor necrosis factor-alfa therapy? A case report and review of the literature

The increased risk to patients on anti-tumor necrosis factor-alfa therapy of developing active tuberculosis supports screening of these patients for latent tuberculosis infection. The current practice of determining the presence of latent tuberculosis infection primarily, and often entirely, depends on the use of tuberculin skin testing (TST). We report a patient with psoriasis on long-term etanercept therapy who had a negative TST result and a positive interferon-gamma release assay result. Similar cases have also been found through a review of the literature. These findings suggest that TST might be unreliable during long-term anti-tumor necrosis factor-alfa therapy. QuantiFeron-TB Gold testing may be a more appropriate primary test in patients with risk factors for false-negative TST results.     

Development of MGUS in psoriatic patients: a possible undiagnosed event during anti‐TNF‐α‐treatment

Background Monoclonal gammopathies are haematological conditions characterized by the clonal proliferation of plasma cells which produce a monoclonal immunoglobulin that accumulates in the blood. They have already been reported during treatment with a range of drugs but never before during treatment with the anti‐TNF‐α treatments: adalimumab, etanercept and infliximab currently used in the therapy of moderate‐severe psoriasis and psoriatic arthritis. Objective This is a case series describing the development of MGUS in psoriatic patients treated with anti‐TNF‐α. Methods Three hundred patients receiving an anti‐TNF‐α treatment for chronic plaque psoriasis or psoriatic arthritis in a clinical setting in Italy, These patients were screened through serum protein electrophoresis to investigate the possible development of MGUS. Results Eight patients were found to have developed monoclonal gammopathy of undetermined significance. The median treatment duration for the eight patients was 1 year with excessive IgG present in five patients, IgM accumulation in one patient and a double monoclonal component in two patients. Conclusion Our data suggest that there may be an association between anti‐TNF‐α therapy and development of MGUS.     

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.