TNF-α Inhibitors In Patients Research Articles

Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area

ObjectivesTo evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment.MethodsPatients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition).ResultsA total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6–12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6–10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5–13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 − 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049].ConclusionThese results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.

Quantification of longitudinal patient-reported burden of adverse drug reactions attributed to the use of TNF-α inhibitors in inflammatory rheumatic diseases: an observational prospective cohort study

ABSTRACT Background There is a lack of knowledge on patient perspectives on adverse drug reactions (ADRs) attributed to the use of biologics. The aim of this study is to quantify the burden over time of ADRs attributed to TNF-α inhibitors in patients with inflammatory rheumatic diseases (IRDs) and investigate whether the burden over time differs between different types of ADRs. Research design and methods Data were used from the Dutch Biologic Monitor (DBM), an observational prospective cohort study for patient-reported ADRs attributed to biologics. Patients with an IRD using a TNF-α inhibitor reporting an ADR, lasting for three consecutive questionnaires, were included. Questionnaires were sent every 2 months and the burden was scored on a 5-point Likert-type scale. Burden scores were analyzed using linear mixed models. Results Data from 166 unique patients reporting 274 ADRs were included. The burden score decreased every month by 0.29 points (95% CI −0.34 – −0.24) on average on a 5-point Likert-type scale. The burden score for infections and infestations decreased significantly faster than the burden score for injection site reactions. Conclusions Patient-reported burden of ADRs attributed to the use of a TNF-α inhibitor in patients with IRDs decreased significantly over time, especially for infections and infestations.

The Use of TNF-α Inhibitors in Active Ankylosing Spondylitis Treatment.

Ankylosing spondylitis (AS) is a challenging disease, characterized by chronic inflammation and structural damage primarily affecting the axial skeleton, while extra-articular manifestations may also appear. This results in the deterioration of patients' quality of life. Over the past few decades, tumor necrosis factor-α (TNF-α) inhibitors have revolutionized the management of AS, offering substantial relief from symptoms and improving patient outcomes. The aim of this review is to assess the efficacy of TNF-α inhibitors in patients with active AS. A search was performed in the PubMed database using the following keywords: ("TNF alpha inhibitors" OR "anti TNF-a" OR "TNF-a inhibitors" OR "anti TNF-alpha" OR "Etanercept " OR "Golimumab" OR "Infliximab" OR "Certolizumab pegol" OR "Adalimumab") AND "ankylosing spondylitis". The search was completed in February 2024, and 35 studies were included in this review following PRISMA guidelines. The findings reveal evidence supporting the efficacy of TNF-α inhibitors in reducing inflammation, preventing structural damage, and enhancing overall well-being in AS patients. Overall, TNF-α inhibitors have emerged as a cornerstone in the therapeutic algorithm against AS with a very satisfactory safety profile.

Prevalence and complication of COVID-19 in patients with ankylosing spondylitis (AS) and its relationship with TNF-a inhibitors.

Ankylosing spondylitis (AS) is a condition that is treated with nonsteroidal anti-inflammatory drugs and biological drugs such as anti tumor necrosis factor alpha (TNF-α). This study examined the prevalence of COVID-19 among individuals with AS and compare it between those receiving and not receiving TNF-α inhibitors. A cross-sectional study was conducted at the rheumatology clinic of Imam Khomeini Hospital in Tehran, Iran. The study included patients with AS who sought treatment at the clinic. Demographic information, laboratory and radiographic findings, and disease activity were recorded through interviews and examinations using a questionnaire. A total of 40 patients were studied over the course of 1 year. Among them, 31 patients were administered anti-TNF-α drugs, with 15 patients (48.3%) receiving subcutaneous Altebrel (Etanercept), 3 patients (9.6%) receiving intravenous Infliximab, and 13 patients (41.9%) receiving subcutaneous Cinnora (Adalimumab). Of the total, 7 patients (17.5%) tested positive for COVID-19, 1 of whom was confirmed through both CT scan and polymerase chain reaction (PCR) testing, while the remaining 6 patients were confirmed only through PCR testing. All patients tested positive for COVID-19 were male, and 6 of them had received Altebrel. Among the 9 AS patients who did not receive TNF inhibitors, 1 patient contracted SARS-CoV-2. The clinical symptoms experienced by these patients were mild, and hospitalization was not required. However, 1 patient who had insulin-dependent type 1 diabetes and was receiving Infliximab required hospitalization. This patient exhibited more severe COVID-19 symptoms, including high fever, pulmonary involvement, dyspnea, and decreased oxygen saturation. No cases of COVID-19 were reported in the Cinnora treatment group. The use of any of the drugs did not demonstrate a significant relationship with the occurrence of COVID-19 in patients. The use of the TNF-α inhibitors in patients with AS, may be associated with reduced hospitalization and death rate in COVID-19 cases.

Uveitis in Children: The Role of Biological Agents in Its Management

We aimed to determine medium and long-term effects of TNF-α inhibitors in patients with pediatric uveitis. This was a retrospective review of medical charts. Included were 50 patients (84 eyes). Mean age at diagnosis was 7.22 ± 4.04 years. At baseline (time of initiation of biologic therapy), all patients had active uveitis. Complete control of uveitis was achieved in 84.52% (n = 71) of eyes, after a median of 3 months (IQR 2 months). Mean LogMAR BCVA at baseline was 0.23 ± 0.44; it remained stable at 12 and 24 months. At baseline, 64% of patients were treated with oral corticosteroids, this decreased to 29.5% at 12 months (p = 0.001) and to 21.9% at 24 months (p < 0.001). Mean time to prednisone dose of ≤0.2 mg/kg/day was 8.1 ± 2.02 months after baseline. A total of 40.5% of eyes were treated with topical steroids at baseline and this significantly decreased to 5.8% at 12 months. Multiple linear regression model was calculated to predict moderate and severe visual loss; only presenting visual acuity accounted for a unique variance in the model. In conclusion, TNF-α inhibitors achieved rapid disease control while enabling a remarkable steroid-sparing effect in children suffering from chronic uveitis. Presenting visual acuity was the sole predictor of moderate to severe visual loss.

Biomarkers and Predictive Factors for Treatment Response to Tumor Necrosis Factor-α Inhibitors in Patients with Psoriasis.

We performed a retrospective and observational study of patients with psoriasis. The aim of this study was to define the laboratory indicators reflecting the treatment response to tumor necrosis factor (TNF)-α inhibitors and the predictors for the treatment response. From January 2010 to June 2022, 28, 15 and 12 patients with psoriasis were treated with infliximab (IFX), adalimumab (ADA) and certolizumab pegol (CZP), respectively. The values of C-reactive protein (CRP), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio decreased in parallel with psoriasis area and severity index (PASI) at weeks 12 and 52 of treatment. The percentage reduction of the CRP was correlated with that of the PASI at week 52 in all patients and subgroups treated with IFX. The percentage reduction of the PLR was correlated with that of the PASI at week 52 in all patients. Linear multivariate regression analyses revealed that the presence of scalp lesions was associated with a high percentage reduction of the PASI at week 52 in the ADA subgroup. The CRP and PLR might act as biomarkers reflecting the treatment response to TNF-α inhibitors in patients with psoriasis. The presence of scalp lesions might be a predictive factor for a high treatment response to ADA in patients with psoriasis.

EFFICACY AND SAFETY OF VEDOLIZUMAB AND TUMOR NECROSIS FACTOR INHIBITORS IN THE TREATMENT OF STEROID-REFRACTORY MICROSCOPIC COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND Tumor necrosis factor (TNF-α) inhibitors and the α4β7 integrin antagonist, vedolizumab have been investigated as a treatment option for patients with steroid-refractory microscopic colitis (MC) with controversial findings. AIMS To perform a systematic review and meta-analysis to evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory MC. METHODS Retrospective cohort studies and case series involving adult patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Outcomes of interest included the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Pooled proportional meta-analyses were used to calculate the overall rates of the primary and secondary endpoints. Heterogeneity was assessed using the I2 statistic. Publication bias was assessed via visual inspection of the funnel plots and using Egger’s regression. All statistical analysis was performed in R using the metafor and meta packages. RESULTS A total of 14 retrospective case series/studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% (95% CI [0.483; 0.776], I2=43% P=0.08), 57.8% (95% CI [0.3895; 0.7571], I2=0%, P=0.7541), and 39.3% (95% CI [0.0814; 0.7492, I2=66%, P=0.02) for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rate was 60.5% (95% CI [0.2772; 0.8953], I2=67%, P=0.03), 45.3% (95% CI [0.1479; 0.7747], I2=0%, P=0.36) and 32.5% (95% CI [0.000; 0.8508], I2=53%, P=0.14) in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biologic-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively. CONCLUSION Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory MC and with a tolerable safety profile. Given the nature of included studies, superiority of either therapy could not be elucidated. Future randomized controlled trials are needed to standardize study protocols, compare vedolizumab with TNF-α inhibitors, and further examine data on patients’ quality of life. Forest plot showing the pooled clinical remission rate at induction in patients with steroid-refractory microscopic colitis receiving (A) vedolizumab or TNF inhibitors (B) Data summary of the meta-analyses of the studies investigating secondary endpoints in patients with refractory MC receiving either (A) vedolizumab or (B) TNF inhibitors ABBREVIATIONS MR, maintenance remission; CR, clinical response; HR, histologic remission; OAE, overall adverse effects.

PD01 Using ELISA Tests For Monitoring Response To Anti-TNFs In Rheumatoid Arthritis: Findings From A NICE Health Technology Assessment

IntroductionPatients with severe rheumatoid arthritis (RA) disease may be treated with tumor necrosis factor (TNF)-α inhibitors. However, their efficacy is reduced by the presence of anti-drug antibodies. The objective of this HTA was to conduct a systematic review to investigate the effectiveness of using enzyme-linked immunosorbent assay (ELISA) tests (Promonitor, IDKmonitor, LISA-TRACKER, RIDASCREEN, MabTrack, and Sanquin Diagnostic Services) to measure levels of the drug and anti-drug antibodies for monitoring response to TNF-α inhibitors in patients with RA.MethodsA range of bibliographic databases including MEDLINE, EMBASE and CENTRAL were searched from inception to November 2018. Studies were eligible for inclusion if they investigated ELISA tests in RA patients receiving treatment with a TNF-α inhibitor who had achieved the treatment target (remission or low disease activity [LDA]) or experienced a primary or a secondary non-response. The tests must compare with standard care where treatment decisions are based on clinical judgements and monitoring using a composite score such as the disease activity score 28 joints (DAS28). Risk of bias was assessed using the Cochrane (ROBINS-1) tool for non-randomized studies.ResultsTwo studies were included. One non-randomized controlled trial (non-RCT) compared standard care with therapeutic drug monitoring using Promonitor test kits in RA patients in remission/LDA receiving adalimumab, and a historically controlled study investigated Sanquin ELISA kits. The non-RCT study showed that there was a non-significant reduction in the risk of flare in the intervention group compared with the control group. Patients’ health-related quality of life outcomes were higher in the intervention group at all visits compared with the control group. However, this study had serious limitations because analyses were not performed using an intention-to-treat approach. The historically controlled study did not provide valid evidence on whether ELISA-based monitoring is clinically effective.ConclusionsThere is only limited, poor evidence available. There are considerable uncertainties on the effectiveness of using ELISA tests for monitoring response to TNF-α inhibitors in RA. Further controlled trials are required.

Analysis and visualization of the course and burden over time of adverse drug reactions (ADRs) attributed to TNFα-inhibitors in patients with inflammatory rheumatic diseases (IRDs)

ABSTRACT Background We aimed to investigate course and burden over time of ADRs attributed to TNFα-inhibitors in IRD-patients, and whether Sankey diagrams and polar plots can visualize this. Research design and methods Data on ADRs experienced during the Dutch Biologic Monitor (January 2017 till December 2022) were used in this study. We selected IRD-patients using a TNFα-inhibitor, reporting skin reactions/infections/injection site reactions and completing ≥3 questionnaires (i.e. the initial report and ≥2 follow-ups). Course was scored as worsening/improving/remaining stable/resolving and as (non-)recurrent. Patients scored burden from 1 (no burden) to 5 (very high burden). Sankey diagrams and polar plots visualized this. Results 202 patients were included, reporting 353 ADRs. Most skin reactions were stable (25.0%). Most infections resolved (50.8%). Injection site reactions were mostly recurrent (72.3%). Skin reactions and infections tended to decrease in burden . Infections had highest burden at start, which mostly decreased over time. Injection site reactions had a low and stable burden. Conclusions Skin reactions attributed to TNFα-inhibitors by IRD-patients are stable with a slightly decreasing burden over time. Infections have highest burden at start but resolved mostly. Injection site reactions have a low and stable burden. Sankey diagrams and polar plots are suitable to visualize this.

Efficacy of TNF-α inhibitors in the treatment of ankylosing spondylitis

Purpose: The study aimed to evaluate and compare the efficacy of TNF-α inhibitors in the treatment of ankylosing spondylitis in everyday medical practice. Materials and methods: We analysed the data of 106 patients with ankylosing spondylitis treated in 2012–2019 with TNF-α inhibitors (etanercept, adalimumab or golimumab) under the drug program of the National Health Fund. The observation period for each patient was 18 months. The disease activity was assessed at 3-month intervals on the basis of BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDAS (Ankylosing Spondylitis Disease Activity Score). Results: The study covered 80 men and 26 women. The mean age of the patients was 37 years. The group receiving etanercept included 50 patients, adalimumab – 39 patients, and golimumab – 17 patients. Due to coexisting offaxial symptoms such as uveitis (n = 20/106) and peripheral arthritis (n = 39/106), some patients were simultaneously receiving classic disease-modifying antirheumatic drugs, i.e. methotrexate (n = 32/106), sulfasalazine (n = 8/106), cyclosporine (n = 5/106), and glucocorticosteroids (n = 14/106). All subgroups showed a significant clinical improvement in the form of a decrease in inflammatory markers and a decrease in disease activity after 3 months of treatment, increasing up to the 6th month. The biological drug was discontinued due to remission (according to BASDAI) in 20/48 patients taking etanercept and in 19/36 patients receiving adalimumab. The observation period following drug discontinuation for both groups was similar and lasted about 7 months. The remission time (according to BASDAI) without treatment was short; 3.55 ± 2.28 months for etanercept vs. 5.21 ± 2.53 months for adalimumab (p = 0.038). Conclusions: The inclusion of TNF-α inhibitors in patients with an unsatisfactory response to treatment with non-steroidal anti-inflammatory drugs resulted in a major reduction of disease activity. There was no statistically significant difference in treatment efficacy between individual TNF-α inhibitors, i.e. etanercept, adalimumab, and golimumab. The group treated with adalimumab was found with a trend towards longer-lasting remission after drug discontinuation, but it was short-lived and a return to treatment was necessary.

The development of universal alopecia during therapy with TNF-α inhibitors in patients with ankylosing spondylitis: description of three cases

Alopecia areata (АA) is an autoimmune multifactorial disease characterized by increased hair loss as a result of morphological and functional changes in hair follicles. АA is divided into four main forms, among which the most severe is the universal form (UA), in which complete hair loss is possible throughout the body. Alopecia in the practice of a rheumatologist can occur with some systemic diseases of the connective tissue, with the use of high doses of chemotherapy drugs and, more recently, with the use of inhibitors of tumor necrosis factors alpha (TNF-α). The article presents 3 clinical cases of the development of UA during therapy with TNF-α. Possible mechanisms are discussed, as well as the role of pro-inflammatory cytokines in the development of this condition.

Health-economic analysis of tocilizumab in patients with rheumatoid arthritis and systemic juvenile arthritis

Rationale . Rheumatoid arthritis (RA) and systemic juvenile arthritis (sJA) are the most frequent rheumatic diseases in adults and adolescents, consequently. Biologics disease modifying antirheumatic drugs (bDMARDs) are eff ective in treatment of RA and s JA. Aim . To perform health-economic analysis of tocilizumab for subcutaneous and intravenous injections in patients with RA and sJA comparing to TNF-α inhibitors. Materials and methods . Cost-minimizing analysis was used from the perspective of healthcare system (accounting for direct medical costs) with the modelling horizon — 1 year. We included into the model cost of RA and sJA bDMARDs, cost of adverse events correction and costs of laboratory and instrumental diagnostic. Results . Cost minimizing ratio of tocilizumab (subcutaneous form) in RA patients comparing to adalimumab (Humira), сertolizumab pegol, golimumab were 111 536; 129 094; 85 244 RUR, consequently favour to tocilizumab. Tocilizumab was less costly comparing to adalimumab (Humira), certolizumab pegol, golimumab by 12.8, 14.5, 10,0 %, consequently. Cost minimizing ratio of tocilizumab in RA patients comparing to adalimumab (Dalibra), etanercept, infl iximab (Remicade) were 40 497; 54 355; 28 419 RUR in favour to comparators. Tocilizumab was more costly comparing to adalimumab (Dalibra) etanercept, infl iximab (Remicade) by 5.6; 7.7; 3.9 %, consequently. Cost minimizing ratio of tocilizumab in sJA patients comparing to kanakinumab, adalimumab (Humira) and adalimumab (Dalibra) were 6 535 234; 478 297 and 323 263 RUR. Tocilizumab was less costly comparing to kanakinumab, adalimumab (Humira) and adalimumab (Dalibra) by 93.3; 50.6 and 41.1 %, consequently. Conclusions . Tocilizumab is economically reasonable comparing to others TNF-α inhibitors in patients with RA and sJA.

Hidradenitis suppurativa: Clinical characteristics and determinants of treatment efficacy.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that causes a significant decline in quality of life. There are numerous treatment options; however, real-life data on the efficacy of these treatments is limited. This study was performed in two centers to describe clinical characteristics and assess treatment outcome in a cohort of 139 patients with HS. Data on demographic and clinical characteristics, Hurley stage and comorbidities were collected from patient charts and evaluated retrospectively. Treatment response was measured with HS clinical response index (HISCR). Mean body mass index was 27.8±4.88. Inflammatory comorbidities were present in 23%. Among first-line drugs systemic doxycycline resulted in 60% HISCR followed by rifampicin-clindamycin combination (46.4%). Isotretinoin had the lowest HISCR (30.7%) in this group. For second-line therapies, all acitretin treated patients achieved response and patients treated with tumor necrosis factor alpha (TNF-α) inhibitors had the highest HISCR. Currently recommended first-line therapies have moderate efficacy in HS. Acitretin appears to be a reasonable alternative for the highly effective TNF-α inhibitors in patients with severe and resistant HS. Overall, these results support that excessive inflammatory response play an important role in pathogenesis of HS.

Genetic polymorphisms in tumour necrosis factor receptors (TNFRSF1A/1B) illustrate differential treatment response to TNFα inhibitors in patients with Crohn’s disease

BackgroundMonoclonal antibodies inhibiting tumour necrosis factor-α (TNFα) signalling pathway (anti-TNFα) have been widely used in Crohn’s disease (CD). However, treatment response varies among patients with CD and the clinical outcome...

Eight-year survival study of first-line tumour necrosis factor α inhibitors in rheumatoid arthritis: real-world data from a university centre registry.

Objective.This study aimed to investigate the efficacy, safety and survival of TNF-α inhibitors in patients with RA.Methods.A total of 178 patients >18 years of age were treated with TNF-α inhibitors. A total of 74 patients were treated with infliximab, 75 with adalimumab and 29 with etanercept. Each patient was followed-up for a period of 8 years.Results.Anti-TNF-α therapy resulted in rapid clinical improvement. The rate of good/moderate response according to EULAR response criteria for the index 28-joint DAS with CRP in the first 6 months was 82% for infliximab, 89.6% for adalimumab and 95.6% for etanercept. The rate of withdrawal in 8 years was 80% for patients on infliximab, 61.4% for patients on adalimumab and 47.6% for patients on etanercept. The main reasons for discontinuation were allergic reactions for infliximab (rate of discontinuation 25.7%) and inefficacy for adalimumab and etanercept (17.5% and 23.8%, respectively). Systemic allergic reactions and infections were significantly more frequent in the infliximab group (P < 0.05 and P < 0.001, respectively). However, there was no significant difference among the three drugs concerning serious infections. According to Kaplan–Meier survival analysis, a significantly faster withdrawal for infliximab patients was depicted compared with adalimumab (P = 0.003) and etanercept (P = 0.019), while adalimumab and etanercept were not statistically different (P = 0.089).Conclusions.TNF-α inhibitors establish an effective therapeutic option in RA showing an acceptable safety profile. Infections and allergic reactions appear more often with infliximab, while serious infections did not differ among them. RA patients treated with infliximab are more likely to discontinue treatment earlier compared with the other alternatives.

Is body composition related to efficacy of biological treatment with TNF-Α inhibitors in patients with crohn’s disease?

Is body composition related to efficacy of biological treatment with TNF-Α inhibitors in patients with crohn’s disease?

Adalimumab is a safe option for psoriasis patients with concomitant hepatitis B or C infection: a multicentre cohort study of 37 patients and review of the literature.

Little data are available about the safety of TNF-α inhibitors in patients with HCV and HBV infection. In particular, data concerning the use of adalimumab in patients with psoriasis and concomitant viral hepatitis are lacking and little is known about the drug's real safety in this context. To assess the long-term safety of adalimumab in a group of 17 consecutive psoriatic patients affected by chronic HBV infection and 20 consecutive psoriatic patients affected by chronic HCV infection. Thirty-seven consecutive patients with psoriasis and concomitant HBV or HCV infection being treated with adalimumab at four Italian referral centres (Modena, Padova, Verona and Turin) were assessed before the treatment and at the end of follow-up. Viral load and radiological studies (echography, Fibroscan) were also carried out in some of the patients. The patients responded well to treatment and did not show any HBV or HCV reactivation in a mean follow-up period of 27 and 40 months, respectively. The fibrosis score in eight HCV patients showed a slight reduction: pretreatment mean value 5.83 and post-treatment mean value 5.65. The use of adalimumab seems to be safe in patients with severe psoriasis and HBV or HCV infection. Nevertheless, large-scale prospective studies will be able to provide vital information on the impact of anti-TNF treatment on hepatic function in patients with psoriasis and concomitant chronic HCV or HBV infection and appropriate monitoring scheduling.

Hepatosplenic T-cell lymphoma arising in patients with immunodysregulatory disorders: a study of 7 patients who did not receive tumor necrosis factor-α inhibitor therapy and literature review.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive extranodal T-cell lymphoma that can arise in patients with underlying immune disorders. Others have suggested that tumor necrosis factor (TNF)-α inhibitor therapy for immune disorders increases the risk of HSTCL. To assess for a potential relationship between HSTCL and the use of TNF-α inhibitors, we searched for patients with HSTCL and underlying immune disorders at our institution. We identified 7 patients with a median age of 38 years. Five patients had Crohn disease, 1 ulcerative colitis, and 1 rheumatoid arthritis. In 6 patients, medication history for the immune disorder was available: 6 patients received 6-mercaptopurine or azathioprine, and 2 patients received steroids; no patients received TNF-α inhibitors. In all 7 patients, the histologic, immunophenotypic, and cytogenetic findings were similar to cases of HSTCL that arise in immunocompetent patients. We reviewed the literature and identified 60 patients with immune disorders who subsequently developed HSTCL. These patients were treated with immunosuppressive drugs in 89%, TNF-α inhibitors in 56%, and both therapies in 54%, and 1 (2%) patient was treated with TNF-α inhibitors only. Our cohort and literature review indicates that TNF-α inhibitor therapy is not essential for the development of HSTCL in patients with immunodysregulatory disorders, and implies that immunosuppressive drugs or other factors (eg, genetic predisposition, chronic antigenic stimulation) may be more critical in the pathogenesis in this context. Although these data are observational, they have implications for the use of TNF-α inhibitors in patients with inflammatory bowel disease and other immunodysregulatory disorders.

PTU-054 Therapeutic Monitoring of TNF-Alpha Inhibitors in Crohn’s Disease; Impact of Nice 2016 Guidelines in a UK District General Hospital

Introduction Therapeutic anti-TNFα monitoring enables optimisation of anti-TNFα therapy. Recently, NICE supported therapeutic monitoring of TNFα inhibitors in patients with Crohn’s disease who fail to respond. However, NICE found the evidence for routine monitoring in patients responding adequately to be insufficient. Small studies show high Infliximab (INF) trough levels and low antibody levels to be associated with successful maintenance of remission. Methods A retrospective review of drug level monitoring in patients with Crohn’s disease taking anti-TNFα drugs was conducted. Patient demographics, IBD type, duration and distribution were recorded. Data were collected to compare against the NICE guidance (DG22). Trough levels, antibody presence and the use of concomitant immunosuppression (thiopurine and/or methotrexate) were noted. Any clinical impact of monitoring was recorded. Results Over 26 months monitoring was performed 93 times in 80 patients. 60% of all monitoring was clinically indicated in patients suspected to be non-responders. The remaining 40% were part of routine care. Of the 80 patients, 53% were male. Median age at first monitoring was 36 years (range 17–79). Median time from diagnosis of Crohn’s was 86 months (range 5–528). 26% had ileal, 30% had colonic and 44% had ileocolonic disease. 30% had stricturing and 8% had penetrating disease phenotypes. 39% had perianal disease. At diagnosis, 19% were aged 16 or below, 56% were aged 17 to 40 and 24% were aged over 40. Onset was unknown in 1%. For all drug monitoring, the median time from anti-TNFα initiation (59% INF; 41% Adalimumab (ADA)) was 60 weeks (range 6–470). 31% had concomitant immunosuppression. Antibodies were detected in 16% (22% INF; 8% ADA). Overall, as a result of monitoring, 49% continued their current anti-TNFα, 37% dose-escalated, 1% de-escalated, 8% stopped, 3% switched to ADA, 1% switched to INF and 1% changed to Vedulizumab. 13% started or increased thiopurine or methotrexate and 8% proceeded to surgery. Of those patients monitored as a part of routine care, 24% dose-escalated, 11% stopped anti-TNFα drugs and 5% switched to ADA. Doses were unchanged in 60%. Conclusion A large proportion of monitoring in our population was for the routine evaluation in patients on anti-TNFα drugs. These patients are now considered outside of NICE practice guidelines. Thus, adhering to NICE guidelines will lead to a substantial reduction in the number of our patients tested. However, in this group, the evaluation of drug levels influenced care in 40% of cases. Thus, further studies are needed to determine the benefits of routine drug level monitoring in stable patients on anti-TNFα drugs. Disclosure of Interest None Declared

CERTOLIZUMAB PEGOL IN THE TREATMENT OF AXIAL SPONDYLOARTHRITIS

The paper gives the results of the RAPID-axSpA study that has evaluated for the first time the efficacy of the tumor necrosis factor-α (TNF-α) inhibitor certolizumab pegol (CZP) in treatment of axial spondyloarthritis (axSpA) clinical forms: already developed ankylosing spondylitis and non-radiographic axSpA. CZP was shown to be effective in all forms of axSpA, whether radiographically detected sacroiliitis was present or absent. This study has also demonstrated for the first time the long-term efficacy of TNF-α inhibitors in patients with initially high C-reactive protein level and/or signs of active sacroiliitis by magnetic resonance imaging.