Discontinuation Of Tumor Necrosis Factor Inhibitors Research Articles

Prevalence and predictors of sustained remission/low disease activity after discontinuation of induction or maintenance treatment with tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic and scoping review

BackgroundTo determine the prevalence of sustained remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) after discontinuation of tumor necrosis factor inhibitors (TNFi), separately in induction treatment and maintenance treatment studies, and to identify predictors of successful discontinuation.MethodsWe performed a systematic literature review of studies published from 2005 to May 2022 that reported outcomes after TNFi discontinuation among patients in remission/LDA. We computed prevalences of successful discontinuation by induction or maintenance treatment, remission criterion, and follow-up time. We performed a scoping review of predictors of successful discontinuation.ResultsTwenty-two induction-withdrawal studies were identified. In pooled analyses, 58% (95% confidence interval (CI) 45, 70) had DAS28 < 3.2 (9 studies), 52% (95% CI 35, 69) had DAS28 < 2.6 (9 studies), and 40% (95% CI 18, 64) had SDAI ≤ 3.3 (4 studies) at 37–52 weeks after discontinuation. Among patients who continued TNFi, 62 to 85% maintained remission. Twenty-two studies of maintenance treatment discontinuation were also identified. At 37–52 weeks after TNFi discontinuation, 48% (95% CI 38, 59) had DAS28 < 3.2 (10 studies), and 47% (95% CI 33, 62) had DAS28 < 2.6 (6 studies). Heterogeneity among studies was high. Data on predictors in induction-withdrawal studies were limited. In both treatment scenarios, longer duration of RA was most consistently associated with less successful discontinuation.ConclusionsApproximately one-half of patients with RA remain in remission/LDA for up to 1 year after TNFi discontinuation, with slightly higher proportions in induction-withdrawal settings than with maintenance treatment discontinuation.

Drug Survival of Tumor Necrosis Factor-Alpha Inhibitors and Switched Subsequent Biologic Agents in Patients with Psoriasis: A Retrospective Study.

This study aimed to retrospectively examine the drug survival of tumor necrosis factor (TNF)-alpha inhibitors and switched subsequent biologic agents after discontinuation of TNF inhibitors. This real-world setting study was conducted at a single academic center. We included patients who were treated with adalimumab (n = 111), certolizumab pegol (n = 12), and infliximab (n = 74) at Jichi Medical University Hospital from 1 January 2010 to 31 July 2021. No significant differences were noted in drug survival between the three TNF inhibitors. The 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. Of the patients who discontinued TNF inhibitors for any reason (n = 137), 105 chose biologics as their subsequent treatment. The subsequent biologics included 31 cases of TNF inhibitors (adalimumab in 20, certolizumab pegol in 1, and infliximab in 10), 19 of interleukin-12/23 inhibitor (ustekinumab), 42 of interleukin-17 inhibitors (secukinumab in 19, brodalumab in 9, and ixekizumab in 14) and 13 of interleukin-23 inhibitors (guselkumab in 11, risankizumab in 1, and tildrakizumab in 1). Cox proportional hazards analysis for the subsequent drugs in cases of discontinuation due to inadequate efficacy revealed that female sex was a predictor of drug discontinuation (hazard ratio 2.58, 95% confidence interval 1.17-5.70) and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug persistence (hazard ratio 0.37, 95% confidence interval 0.15-0.93). Interleukin-17 inhibitors may be a favorable option for patients who need to switch from TNF inhibitors due to inadequate efficacy. However, this study is limited by the small number of cases and its retrospective design.

Discontinuation of tofacitinib and TNF inhibitors in patients with rheumatoid arthritis: analysis of pooled data from two registries in Canada

ObjectivesThe similarity in retention of tumour necrosis factor inhibitors (TNFi) and tofacitinib (TOFA) was previously reported separately by the Ontario Best Practices Research Initiative and the Quebec cohort Rhumadata. However,...

Can Biologics Be Discontinued in Patients with Psoriatic Arthritis in Stable Remission? A Prospective Single‐CenterClinical and Ultrasound Study

Biologic disease‐modifying antirheumatic drugs (bDMARDs) and particularly tumor necrosis factor inhibitors (TNFi) have dramatically changed the natural history of psoriatic arthritis (PsA), making complete clinical remission possible in most patients. However, TNFi drugs are not without potential adverse effects such as increased infectious risk. In addition, their extensive use is associated with a significant economic burden. This prospective longitudinal cohort study involving 45 PsA patients treated with TNFi in stable remission aimed to evaluate by both clinical examination and ultrasound timing and predictive factors of disease relapse after discontinuation of TNFi treatment. Thirty‐nine (86.6%) of 45 enrolled patients experienced disease relapse during the follow‐up period, while six patients (13.4%) maintained remission beyond the scheduled 104 weeks. The median survival time of drug‐free remission after TNFi discontinuation was 24 weeks (95% confidence interval (CI): 22.6–25.4). Disease relapse was characterized by marked clinical and ultrasound worsening of dermatologic and rheumatologic conditions. However, resuming previously discontinued treatment allowed all patients to quickly regain clinical remission. Interestingly, axial involvement was a key feature of the symptomatological pattern of disease relapse, being the main reason for treatment restart in 26% of our cohort. Based on a multivariate Cox model, three variables (VAS pain, tender joint count, and swollen joint count) of the clinical assessment performed at the time point of TNFi treatment onset negatively influenced the time to disease relapse. In conclusion, temporary discontinuation of TNFi drugs is feasible and relatively safe. However, as few predictors of the risk and timing of disease relapse have been identified, patients should be closely monitored when therapy is discontinued.

Development of pulmonary sarcoidosis in Crohn\u2019s disease patient under infliximab biosimilar treatment after long-term original infliximab treatment: a case report and literature review

BackgroundInflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor inhibitors (TNF-I) are effective for the treatment. Recently, biosimilars of TNF-I, such as CT-P13, have been developed and are thought to possess equal efficacy and safety to the original TNF-I. Sarcoidosis is also a systemic granulomatous disease of unknown etiology. In steroid-resistant cases of sarcoidosis, TNF-I have been reported effective for achieving resolution. However, the progression of sarcoidosis due to the TNF-I also has been reported. We herein report a case of pulmonary sarcoidosis with a Crohn’s disease (CD) patient developed after a long period administration (15 years) of TNF-I.Case presentationsA 37-year-old woman with CD who had been diagnosed at 22 years old had been treated with the TNF-I (original infliximab; O-IFX and infliximab biosimilar; IFX-BS). Fifteen years after starting the TNF-I, she developed a fever and right chest pain. Chest computed tomography (CT) revealed clustered small nodules in both lungs and multiple enlarged hilar lymph nodes. Infectious diseases including tuberculosis were negative. Bronchoscopic examination was performed and the biopsy specimens were obtained. A pathological examination demonstrated noncaseating granulomatous lesions and no malignant findings. TNF-I were discontinued because of the possibility of TNF-I-related sarcoidosis. After having discontinued for four months, her symptoms and the lesions had disappeared completely. Fortunately, despite the discontinuation of TNF-I, she has maintained remission.ConclusionsTo our knowledge, this is the first case in which sarcoidosis developed after switching from O-IFX to IFX-BS. To clarify the characteristics of the cases with development of sarcoidosis during administration of TNF-I, we searched PubMed and identified 106 cases. When developing an unexplained fever, asthenia, uveitis and skin lesions in patients with TNF-I treatment, sarcoidosis should be suspected. Once the diagnosis of sarcoidosis due to TNF-I was made, the discontinuation of TNF-I and administration of steroid therapy should be executed promptly. When re-starting TNF-I, another TNF-I should be used for disease control. Clinicians should be aware of the possibility of sarcoidosis in patients under anti-TNF therapy.

Methotrexate Reduces the Probability of Discontinuation of TNF Inhibitors in Seropositive Patients With Rheumatoid Arthritis. A Real-World Data Analysis

Tumor necrosis factor inhibitors (TNFi) are widely used for the treatment of patients with rheumatoid arthritis (RA), however a considerable percentage of patients discontinued the therapy. The aim of this study is to explore real-world TNFi survival, stratified for seropositivity, and to determine the factors that may influence it. This is a retrospective, observational and longitudinal study, using real-world data of patients, who started their first TNFi therapy between 1999 and 2018 from the RA-PAZ cohort. Patients were considered seropositive if they showed positive serum levels of either RF, ACPA, or both. Treatment survival was analyzed using Kaplan-Meier curves, and Cox proportional hazards models were used to compare the risks of TNFi discontinuation for seronegative and seropositive patients. Of the included 250 patients, 213 (85%) were seropositive. Results showed that TNFi survival did not depend on seropositivity status. However, median survival time was significant longer for seropositive patients who received concomitant MTX compared to patients who did not receive it (median [95% CI]: 3.3 yr. [2.3–4.2] vs. 2.6 yr. [1.7–3.6], respectively; p = 0.008). Furthermore, seropositive patients who received concomitant MTX were 49% less likely to discontinue TNFi therapy than patients who did not receive it (HR: 0.51; 95% CI: 0.35–0.74). In addition, we found that in seropositive patients, the use of prednisone throughout the TNFi treatment was associated with a higher likelihood of therapy discontinuation (OR: 2.30; 95% CI: 1.01–5.23). In conclusion, these data provide evidence to support the use of concomitant MTX in seropositive patients to prolong the effectiveness and the survival of the TNFi therapy. Moreover, the co-administration of prednisone in seropositive patients receiving TNFi was highly associated with TNFi discontinuation.

Comparison of long-term efficacy between biological agents following tumor necrosis factor inhibitor failure in patients with rheumatoid arthritis: a prospective cohort study.

Background:Currently, there is contradictory evidence regarding the best strategy to follow after discontinuation of a first biological agent in patients with rheumatoid arthritis (RA). We aimed to compare the long-term efficacy of switching to a second tumor necrosis factor inhibitor (TNFi) versus biopharmaceuticals with other mechanisms of action (non-TNFi) in patients with RA who previously failed a first TNFi.Methods:This prospective cohort study analyzed data from 127 patients who discontinued a previous TNFi between 1999 and 2016. Disease activity was assessed at baseline and at 6, 12, and 24 months (m-6, m-12, m-24) after switching. Primary outcome was the proportion of patients achieving good/moderate EULAR response (E-resp). Factors associated with clinical outcomes were assessed using univariate and multivariate logistic regression models.Results:Seventy-seven (61%) patients received a second TNFi and 50 (39%) switched to a non-TNFi. At m-6 and m-12, no differences were observed between groups; nevertheless, at m-24, the proportion of patients with E-resp was higher in the non-TNFi group (49% TNFi group versus 77% non-TNFi group; p = 0.002). In regression models, switching to a non-TNFi was significantly associated with E-resp at m-24 (odds ratio = 3.21; p = 0.01). When assessing the response to the second biological agent based on the reason for discontinuation of the first TNFi, similar results were obtained; at m-24, patients who discontinued the first TNFi due to inefficacy (either primary or secondary) experienced a better E-resp if they had switched to a non-TNFi (primary inefficacy: 52% TNFi group versus 79% non-TNFi group, p = 0.09; secondary inefficacy: 50% versus 76%, p = 0.03).Conclusion:In our cohort of RA patients who discontinued a first TNFi, those who switched to a non-TNFi were three times more likely to attain a sustained clinical response, regardless of whether they had discontinued the first biologic due to a primary or secondary inefficacy.

Posttraumatic Stress Disorder, Depression, Anxiety, and Persistence of Methotrexate and TNF Inhibitors in Patients with Rheumatoid Arthritis.

ObjectiveTo examine the relationship of posttraumatic stress disorder (PTSD) with earlier treatment discontinuation and medication adherence in US veterans with rheumatoid arthritis (RA).MethodsVeterans Affairs (VA) administrative data (2005‐2014) were used to define unique dispensing episodes of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) for veterans with RA. Diagnosis codes were used to categorize patients into mutually exclusive groups: PTSD (with/without depression/anxiety), depression/anxiety without PTSD, and neither psychiatric diagnosis. Multivariable Cox proportional hazards models were used to evaluate associations between psychiatric diagnoses and time to disease‐modifying antirheumatic drug discontinuation (lapse in refill >90 days). Multivariable logistic regression was used to examine associations of diagnoses with medication nonadherence (proportion of days covered <0.8).ResultsThere were 15 081 dispensing episodes of MTX and 8412 dispensing episodes of TNFi. PTSD was independently associated with a greater likelihood of earlier discontinuation of both MTX (hazard ratio [HR] 1.15 [1.10‐1.21]) and TNFi (HR 1.20 [1.13‐1.28]). Depression/anxiety had a comparable risk of discontinuation for both MTX (HR 1.14 [1.10‐1.19]) and TNFi (HR 1.16 [1.10‐1.22]). Depression/anxiety, but not PTSD, was associated with higher odds of MTX (odds ratio [OR] 1.12 [1.03‐1.22]) and TNFi (OR 1.14 [1.02‐1.27]) nonadherence.ConclusionVeterans with RA and comorbid PTSD, depression, or anxiety had poor persistence of MTX and TNFi therapies. These results suggest that earlier discontinuation and low adherence to therapy among patients with RA with these psychiatric comorbidities may contribute to worse disease outcomes. Mechanisms by which these comorbidities contribute to lower adherence deserve further investigation and may lead to targeted interventions to improve disease outcomes.

Real-world Longterm Effectiveness of Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis Patients from the Rheumatic Diseases Portuguese Register.

To assess longterm effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA) registered in the Rheumatic Diseases Portuguese Register, exposed to at least 1 TNFi, prospectively followed between 2001 and 2017. Kaplan-Meier analysis was performed for first-, second-, and third-line TNFi. Responses included European League Against Rheumatism (EULAR) criteria, Disease Activity Index for Psoriatic Arthritis (DAPSA), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) at 3 and 6 months. Baseline predictors of discontinuation and response were studied using Cox and multivariable multinomial/logistic regression models. The 750 patients with PsA showed drug retention of 4.1 ± 3.4 years (followup 5.8 ± 3.8 yrs) for first TNFi. Switching to a second (189 patients) or third (50 patients) TNFi further decreased survival by 1.1 years. Female sex, higher baseline 28-joint count Disease Activity Score, and infliximab were predictors of first TNFi discontinuation. After 6 months of the first TNFi, 48.7% of patients achieved a good EULAR criteria response and 20.9% were in DAPSA remission. There were 11.4% in MDA, and 56.4% had a good ASDAS. Responses to the second TNFi were significantly inferior compared to responses to the first TNFi. Female sex and higher baseline Health Assessment Questionnaire-Disability Index were negatively associated with good EULAR response at 3 months, and obesity decreased the chance of response at 6 months. In this study, switching to a second or third TNFi was associated with significantly lower drug survival and response rates for patients with axial and peripheral PsA subtypes. More successful therapeutic approaches will require considering the effect of sex and obesity on TNFi effectiveness.

Tumor necrosis factor-α inhibitor-induced psoriasis in juvenile idiopathic arthritis patients.

The development of psoriasis while on tumor necrosis factor inhibitors (TNFi) is a paradoxical effect of agents that treat psoriasis. There is a paucity of data available on this entity in juvenile idiopathic arthritis (JIA). Our objectives were to determine the prevalence of TNFi-induced psoriasis in patients with JIA at two pediatric centers, and psoriasis response to therapeutic modifications. We performed retrospective chart review on patients with JIA treated with TNFi (adalimumab, etanercept, infliximab) who developed psoriasis. TNFi-induced psoriasis was defined as an incident diagnosis of psoriasis after starting a TNFi. Patients with personal histories of psoriasis prior to TNFi therapy were excluded. Following diagnosis, responses to medication changes were defined based on physician assessments. Nine of 166 (5.4%) patients on TNFi for JIA were diagnosed with TNFi-induced psoriasis. All cases were female. One had a family history of psoriasis. The median age was 10 (range 2-16) years. Five (55%) patients experienced scalp psoriasis, including four (44%) with alopecia. Two (22%) patients achieved significant improvement after switching to different classes of biologic agents, while three (33%) patients had significant improvement following discontinuation of biologic therapy. One of fivepatients who switched to a different TNFi had complete resolution, while four had worsening symptoms or partial improvement. Our findings demonstrate the prevalence of TNFi-induced psoriasis in JIA at two centers. Though larger studies are needed, our data suggest discontinuation of TNFi or biologic class switching should be considered as treatment strategies in select patients.

Association between seropositivity and discontinuation of tumor necrosis factor inhibitors due to ineffectiveness in rheumatoid arthritis.

Discontinuation of biologic therapy in rheumatoid arthritis is attributable to various reasons, with the most important cause being insufficient response. In this study, we investigated the association between rheumatoid factor (RF) and anti-citrullinated protein autoantibody (ACPA) status and the discontinuation of tumor necrosis factor inhibitors (TNFi) therapy due to insufficient response in bio-naïve rheumatoid arthritis (RA) patients. This study included patients enrolled in the Tsurumai Biologic Communication Registry in Japan. The crude comparison of TNFi discontinuation due to ineffectiveness between seropositive and seronegative patients was analyzed using the cumulative incidence function of competing events and Gray test. We assessed the associations between baseline patient characteristics and discontinuation of TNFi therapy due to insufficient response using Fine-Gray proportional hazard regression. Fine-Gray proportional hazard analysis considered competing events of interest, including insufficient response, adverse event, palliation, and personal reasons. Of 1237 patients evaluated, 79.3% were positive for RF and 85.4% for ACPA; 72.6% were double positive and 11.1% were double negative. TNFi therapy had been discontinued because of insufficient response at 200weeks in 19.8% RF-positive, 16.7% RF-negative, 23.0% ACPA-positive, and 13.8% ACPA-negative patients. There was a significantly higher discontinuation rate due to insufficient response in ACPA-positive patients than in ACPA-negative patients using Gray test, with a similar trend as that for RF status. RF positivity was significantly predictive of the discontinuation of TNFi therapy due to ineffectiveness using Fine-Gray proportional hazard regression analysis after adjusting for baseline characteristics, including age, sex, stage, class, disease activity at baseline, methotrexate use, and prednisolone use [hazard ratio 1.73 (95% confidence interval 1.07-2.80)]. Using Fine-Gray proportional hazard regression, we demonstrated that RF positivity was related to a higher discontinuation rate of TNFi therapy due to ineffectiveness in bio-naïve RA patients. Key Points • RF positivity is related to a higher discontinuation rate of TNFi therapy due to ineffectiveness. • ACPA is not predictive of a discontinuation of TNFi therapy due to ineffectiveness.

No Association of Discontinuing Tumor Necrosis Factor Inhibitors Before Gestational Week Twenty in Well-Controlled Rheumatoid Arthritis and Juvenile Idiopathic Arthritis With a Disease Worsening in Late Pregnancy.

To investigate whether the discontinuation of tumor necrosis factor inhibitors (TNFi) during pregnancy is associated with any changes of the disease course in women with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Pregnant women with RA and JIA from the US and Canada were enrolled in the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project, a prospective cohort study. Information about medication and disease activity (patient-reported outcome measures) was collected prior to gestational week 20 and at gestational week 32. Associations between patterns of TNFi continuation or discontinuation and disease activity changes were tested in unadjusted and multivariate analyses. Among 490 women (397 with RA, 93 with JIA) enrolled between 2005 and 2017, 122 (24.9%) discontinued a TNFi before gestational week 20, 201 (41.0%) received a TNFi beyond week 20, and 167 (34.1%) did not receive a TNFi during pregnancy. At the time of enrollment, disease activity was low to minimal in 72.9% of women. TNFi discontinuation was not associated with a clinically important worsening of patient reported outcome measures at the third trimester. Univariate but not multivariate analysis showed that women receiving TNFi beyond week 20 were more likely to experience improved disease activity scores at the third trimester. Discontinuing TNFi before gestational week 20 seems feasible in women with RA and JIA who enter pregnancy with well-controlled disease.

Effectiveness and Persistence of The First Tumor Necrosis Factor Inhibitor In Portuguese Psoriatic Arthritis Patients

Tumor necrosis factor inhibitors (TNFi) dramaticaly improved the management of psoriatic arthritis (PsA). Nevertheless, a significant proportion of patients do not respond and/or are intolerant to TNFis. The objective of this work was to assess the effectiveness, measured by response rates and drug survival, and the main reasons for TNFi discontinuation, in PsA patients. This was a retrospective non-interventional study of PsA patients registered at the Rheumatic Diseases Portuguese Registry, with at least 1 TNFi prescription. Data was analyzed at 0, 3, 6, 12, 24, 36 and 48 months after starting a first TNFi. Response was measured by composite disease activity (DAS, ACR, PsARC, BASDAI, ASDAS, MDA) and functional (HAQ) indices. Drug survival was assessed by Kaplan-Meier survival analysis. In all analyses significance level was set at 0.05. 705 PsA patients were included, with a mean age of 52.5 years (±13.3); 50.8% (n=358) female. 185 patients (26.24%) treated with adalimumab, 322 (45.67%) etanercept, 100 (14.18%) golimumab and 98 (13.90%) with infliximab. The average response rates, measured by composite disease activity and functional indices, are shown in Table 1. The average drug persistence was of 31.79±17.03 months for TNFi as a group, with 205 (29.08%) of discontinuations during a period of 4 years of follow-up. The main reasons for discontinuation of the first TNFi were: non-response/loss of response 111 (54.15%), adverse event 48 (23.41%), surgery 6 (2.93%), refusal to continue treatment, 4 (1.95%), loss to follow-up 3 (1.46%), pregnancy 4 (1.95%), death 2 (0.98%), remission 2 (0.98%), and others 10 (4.88%). PsA patients receiving a first TNFi will persist on treatment for an average of 2.6 years with treatment discontinuations rates of 29.08%. Non-response/loss of response constitutes the major reason for treatment discontinuation in this population.

Effect of Comedication With Conventional Synthetic Disease‐Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study

ObjectiveTo evaluate whether use of comedication with conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA).MethodsPatients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time‐fixed) variables were included, and a second model incorporating time‐varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score.ResultsIn total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow‐up time of 2.5 years (range 0.08–13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59–1.16) nor during follow‐up in the model adjusted for time‐varying covariates (HR 1.07, 95% CI 0.68–1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment.ConclusionComedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.

The Effect of Comedication With a Conventional Synthetic Disease-Modifying Antirheumatic Drug on Drug Retention and Clinical Effectiveness of Anti-Tumor Necrosis Factor Therapy in Patients With Axial Spondyloarthritis.

To explore the effect of comedication with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) on drug retention and clinical effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (SpA). The study included all patients starting treatment with a TNFi in a large prospective cohort of axial SpA patients (Swiss Clinical Quality Management in axial SpA). Crude drug retention was analyzed using the Kaplan-Meier method, and in adjusted analyses, Cox proportional hazards regression was used to model TNFi discontinuation. We evaluated multiple disease activity measures and validated clinical response criteria over time. A total of 2,765 TNFi treatment courses were included from 1,914 patients with axial SpA, 20.4% in combination with a conventional synthetic DMARD. In unadjusted analyses, the monotherapy group had significantly shorter median TNFi retention time (32.7 months) compared to the cotherapy group (39.1 months) (P = 0.04). In multivariate adjusted analyses, the monotherapy group had significantly lower TNFi retention, with a hazard ratio (HR) of 1.17 (95% confidence interval [95% CI] 1.01-1.35). This effect was even larger when only infliximab-treated patients were considered, with an HR for monotherapy of 1.36 (95% CI 1.06-1.74). Clinical response rates were almost identical at 1 year, with a change in the Bath Ankylosing Spondylitis Disease Activity Index of -2.02 and -2.00 (P = 0.83) and a change in the Ankylosing Spondylitis Disease Activity Score using C-reactive protein of -1.14 and -1.12 (P = 0.45) in the monotherapy and cotherapy groups, respectively. We demonstrate an association between the combination of a TNFi with conventional synthetic DMARDs and improved drug retention in patients with axial SpA, particularly in the subgroup of patients with infliximab.

Efficacy of add-on tacrolimus on methotrexate to maintain clinical remission after rediscontinuation of a tumor necrosis factor inhibitor in rheumatoid arthritis patients who relapsed shortly after discontinuation of the same tumor necrosis factor inhibitor due to clinical remission

Objectives: To describe the efficacy of adding tacrolimus to maintain remission in patients with rheumatoid arthritis (RA) on methotrexate after discontinuation of tumor necrosis factor inhibitor (TNFi) therapy.Methods: Consecutive patients with RA, who resumed a TNFi to treat flares after initial TNFi-free remission and discontinued a TNFi again after achieving remission and adding tacrolimus were enrolled. The lengths of remission after discontinuation of TNFi without or with tacrolimus were analyzed.Results: Thirteen TNFi-free periods in six patients, in which seven were without and six were with tacrolimus were analyzed. All were seropositive females with a median age of 46 years and symptom duration of 1.2 years at the onset of TNFi therapy. Two were treated with infliximab and four were with etanercept. The median dose of tacrolimus was 2 mg/day with trough level of 4.5 ng/ml. The length of time to flare after discontinuation of TNFi therapy with tacrolimus was significantly longer than those without tacrolimus (median 107 weeks [range 4–207] versus 13 weeks [2–36]). After adding tacrolimus, only one patient resumed TNFi therapy and three had no flare until final observation.Conclusions: Add-on tacrolimus was effective in maintaining TNFi-free remission in patients with RA who ever relapsed after TNFi-free remission.

Risk of postoperative infections and the discontinuation of TNF inhibitors in patients with rheumatoid arthritis: A meta-analysis

ObjectiveTo determine whether continuation of tumor necrosis factor inhibitors (TNFi) before surgery increases the risk of surgical site infection (SSI) in rheumatoid arthritis (RA) patients. MethodsA systematic review of the literature was conducted from January 2000 to May first 2014, using the databases of PubMed, Cochrane review, Embase, and manual research of abstracts presented in scientific congresses. Most included studies were retrospective. We compared the risk of SSI in the case of discontinuation of TNFi versus continuing TNFi treatment before a surgery. ResultsSix studies, with a total of 2743 patients (1360 in the group continuing TNFi agent and 1383 in the group discontinuing TNFi) were included. There was a decreased risk of SSI in patients stopping TNFi (relative risk [RR]=0.62 [95% confidence interval [CI] 0.43–0.89], P=0.99, I2=0%). Concerning overall complications, there was also a decreased risk in patients discontinuing TNFi treatment (RR=0.60 [95% CI 0.42–0.87], P=0.26, I2=25%). ConclusionThis meta-analysis showed an increased risk of SSI in patients under TNF inhibitor, and a decreased risk of SSI in case of interruption of treatment during the perioperative time.

FRI0256 Risk of Relapse after Discontinuing Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis Patients with Low Disease Activity: A Systematic Review and Meta-Analysis

BackgroundClinical remission or low disease activity (LDA) are now realistic targets in the management of patients with rheumatoid arthritis (RA), especially in early disease and thanks to biologic treatments. The...

FRI0200 Relative effectiveness of rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis and an inadequate response to a single previous TNF inhibitor: Results from switch-RA, a global, comparative-effectiveness, observational study

BackgroundRecent studies indicate that RA patients (pts) with an inadequate response (IR) to a tumor necrosis factor inhibitor (TNFi) may achieve greater clinical benefit from switching to rituximab (RTX) than...