TNF-α Blockers Research Articles

TNF-alpha inhibition could reduce biomarkers of endothelial dysfunction in patients with moderate to severe psoriasis: A 52-week echo-Doppler based quasi-experimental study

ObjectivesPsoriasis is associated to endothelial dysfunction, which causes impaired vascular functioning. TNF-α blockers have shown the ability to improve vascular functioning in psoriasis. The nailfold vessel resistance index (NVRI) assesses microvascular functioning at nailfold. The objectives of the study are to assess the effect of the TNF-α inhibition with adalimumab on NVRI. Material and methodsQuasi-experimental study. Fifteen patients with moderate-severe psoriasis received adalimumab 40mg sc according to label information. Participants were assessed at baseline and at 12, 24 and 52 weeks after study intervention. ResultsA reduction of −0.09±0.02 (p<.01) in NVRI and a −11.2±2.41ng/ml (p<.001) in E-selectin was observed at week 52. ConclusionsAdalimumab could produce a progressive and sustained reduction of vessel resistance at nailfold and E-selectin in patients with psoriasis.

TNF-α exerts potent anti-rotavirus effects via the activation of classical NF-κB pathway

Active virus-host interactions determine the outcome of pathogen invasions. It has been shown that in isolated dendritic cells (DCs), rotavirus can induce the expression of tumor necrosis factor α (TNF-α), a vital cytokine mediating host immune responses. However, the role of TNF-α in rotavirus infection is unknown. In this study, we demonstrated that TNF-α has potent anti-rotavirus effects, independent of type I interferon production. Blocking of TNF-α by infliximab, a clinically available TNFα antibody, totally abrogated this effect. Mechanistic studies revealed that the anti-rotavirus effect of TNF-α was achieved by NFκB-regulated genes via the activation of classical nuclear factor κB (NF-κB) signaling. Our study reveals the pivotal role and the mechanism-of-actions of TNF-α in the host defense against rotavirus. Thus, this knowledge may contribute to the better understanding of the complexity of rotavirus-host interactions.

Trivalent soluble TNF Receptor, a potent TNF-\u03b1 antagonist for the treatment collagen-induced arthritis

Tumor necrosis factor is a major pro-inflammatory cytokine which triggers various physiological consequences by binding to and trimerizing its receptors, and has been the single most sought-after drug target for intervening autoimmune diseases such as rheumatoid arthritis and psoriasis. However, current TNF-α blockers, including soluble receptor-Fc fusion and therapeutic antibodies, are all dimeric in structure, whereas their target TNF-α itself is homotrimeric in nature. Here we describe the development of a trivalent soluble TNF receptor and show that it is a more potent than the dimeric TNF receptor decoys in inhibiting TNF-α signaling both in vitro and in vivo. The process involves gene fusion between a soluble receptor TNFRII with a ligand binding domain and a trimerization tag from the C-propeptide of human collagen (Trimer-Tag), which is capable of self-assembly into a covalently linked trimer. We show that the homotrimeric soluble TNF receptor (TNFRII-Trimer) produced with such method is more potent in ligand binding kinetics and cell based bioassays, as well as more efficacious in attenuating collagen-induced arthritis (CIA) in a mouse model than its dimeric TNFRII-Fc counterpart. Thus, this work demonstrates the proof of concept of Trimer-Tag and provides a new platform for rational designs of next generation biologic drugs.

Targeting TNF-α against dengue virus-induced neurotoxicity and acute viral encephalitis-like symptoms

Abstract Pro-inflammatory tumor necrosis factor α (TNF-α) facilitates dengue virus (DENV) infection in endovascular dysfunction and neurotoxicity. The introduction of TNF-α blocking therapy with antibodies and antagonists is performed for testing its therapeutic effects in this study. In DENV-infected mice, TNF-α was produced in the brains accompanied by the progression of neurotoxicity and encephalitis. DENV infection caused loss in hippocampal neurons with TNF-α expression around the damaged regions. Additionally, immunostaining showed the induction of apoptosis in hippocampal neurons. TNF-α was expressed in active microglia as well as astrocytes of DENV-infected mice. TNF-α facilitated DENV-induced neurotoxicity in vitro in murine Neuro-2a cells. By using a currently established encephalitic mice model that DENV infection caused progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection, TNF-α transgenic mice represented the progressive disease development while administration of neutralizing TNF-α antibody reduced dengue encephalitis and mortality. These results demonstrate an immunopathogenesis of TNF-α for mediating DENV-induced encephalitis-associated neurotoxicity and targeting TNF-α can be used as a strategy against dengue encephalitis.

Second-Generation SYK Inhibitor Entospletinib Ameliorates Fully Established Inflammation and Bone Destruction in the Cherubism Mouse Model.

Cherubism is a craniofacial disorder characterized by maxillary and mandibular bone destruction. Gain-of-function mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for the excessive bone resorption caused by fibrous inflammatory lesions. A homozygous knock-in (KI) mouse model for cherubism (Sh3bp2KI/KI ) develops autoinflammation resulting in systemic bone destruction. Although administration of the TNF-α blocker etanercept to neonatal Sh3bp2KI/KI mice prevented the disease onset, this therapy was not effective for adult Sh3bp2KI/KI mice or human cherubism patients who already had lesions. Because genetic ablation of spleen tyrosine kinase (SYK) in myeloid cells rescues Sh3bp2KI/KI mice from inflammation, we examined whether SYK inhibitor administration can improve fully developed cherubism symptoms in adult Sh3bp2KI/KI mice. Entospletinib (GS-9973) was intraperitoneally injected into 10-week-old Sh3bp2KI/KI mice every day for 6 weeks. Treatment with GS-9973 improved facial swelling and histomorphometric analysis of lung and liver tissue showed that GS-9973 administration significantly reduced inflammatory infiltrates associated with decreased levels of serum TNF-α. Micro-computed tomography (μCT) analysis showed that GS-9973 treatment reduced bone erosion in mandibles, calvariae, and ankle and elbow joints of Sh3bp2KI/KI mice compared to Sh3bp2KI/KI mice treated with dimethyl sulfoxide (DMSO). Taken together, the results demonstrate that administration of the SYK inhibitor ameliorates an already established cherubism phenotype in mice, suggesting that pharmacological inhibition of SYK may be a treatment option for cherubism patients with active disease progression. © 2018 American Society for Bone and Mineral Research.

Le poumon de la sarcoïdose

Sarcoidosis is a granulomatous disease of unknown cause with almost constant lung involvement and a natural history difficult to predict. Diagnosis is based on triple context with an evocative clinical and radiological presentation, the demonstration of non-caseating and typical granulomas by biopsy samples of superficial lesions, perendoscopic bronchial biopsies or endobronchial ultrasound-guided transbronchial needle aspiration and the exclusion of other causes of granulomatosis. Corticotherapy is the first-line of treatment and is indicated in almost half of patients. Second – and third-line of treatments are respectively cytotoxic agents and TNF-α blockers. Severe pulmonary sarcoidosis including fibrosis, pulmonary hypertension, bronchial stenosis and aspergillosis are the leading causes of morbidity and mortality. The challenge in pulmonary involvement management is especially not to miss an alternative diagnosis, to know when and how to treat patients and to better target those at risk of developing severe forms.

Expression levels of selected genes can predict individual rheumatoid arthritis patient response to tumor necrosis factor alpha blocker treatment

Objectives: Rheumatoid arthritis (RA) patients have many therapeutic options; however, tools to predict individual patient response are limited. The Genefron personal diagnostic kit, developed by analyzing large datasets, utilizes selected interferon stimulated gene expressions to predict treatment response. This study evaluates the kit’s prediction accuracy of individual RA patients’ response to tumor necrosis alpha (TNFα) blockers.Methods: A retrospective analysis was performed on RA patients reported in published datasets. A prospective analysis assessed RA patients, before and 3 months after starting a TNFα blocker. Clinical response was evaluated according to EULAR response criteria. Blood samples were obtained before starting treatment and were analyzed utilizing the kit which measures expression levels of selected genes by quantitative real time polymerase chain reaction (PCR). ROC analysis was applied to the published datasets and the prospective data.Results: The Genefron kit analysis of retrospective data predicted the response to a TNFα blocker in 53 of 61 RA patients (86.8% accuracy). In the prospective analysis, the kit predicted the response in 16 of 18 patients (89% accuracy) achieving a EULAR moderate response, and in 15 of 18 patients achieving a EULAR good response (83.3% accuracy). ROC analysis applied to the two published datasets yielded an AUC of 0.89. ROC analysis applied to the prospective data yielded an AUC of 0.83 (sensitivity – 100%, specificity – 75%) The statistical power obtained in the prospective study was .9.Conclusion: The diagnostic kit predicted the response to TNFα blockers in a high percentage of patients assessed retrospectively or prospectively. This personal kit may guide selection of a suitable biological drug for the individual RA patient.

Pregnancy After Tubal Sterilization in a Woman Treated with Biologics for Severe Psoriasis.

Little is known about whether immunosuppressed patients mount the immunological response necessary to ensure tubal occlusion. Theoretical concern for non-occlusion has limited the use of hysteroscopic sterilization in patients on immunosuppressive therapies. The effects of tumor necrosis factor-alpha (TNF-α) blockers and interleukin (IL)-17 inhibitors on contraception and pregnancy for patients with psoriasis are poorly documented. We report a case of pregnancy that ended in miscarriage in a patient treated first with TNF-α and then with IL-17 inhibitors for severe psoriasis after tubal sterilization with micro-inserts. Our observation suggests that the efficacy of tubal sterilization by micro-inserts may be impaired by these two biologics and that the risk of miscarriage may be increased in women with psoriasis treated with secukinumab.

Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis.

The binding of the tumor necrosis factor α (TNFα) to its cognate receptor initiates many immune and inflammatory processes. The drugs, etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), certolizumab-pegol (Cimzia®), and golimumab (Simponi®), are anti-TNFα agents. These drugs block TNFα from interacting with its receptors and have enabled the development of breakthrough therapies for the treatment of several autoimmune inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, and psoriatic arthritis. In this review, we describe the latest works on the structural characterization of TNFα–TNFα antagonist interactions related to their therapeutic efficacy at the atomic level. A comprehensive comparison of the interactions of the TNFα blockers would provide a better understanding of the molecular mechanisms by which they neutralize TNFα. In addition, an enhanced understanding of the higher order complex structures and quinary structures of the TNFα antagonists can support the development of better biologics with the improved pharmacokinetic properties. Accumulation of these structural studies can provide a basis for the improvement of therapeutic agents against TNFα for the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases in which TNFα plays an important role in pathogenesis.

Anti-adalimumab antibodies in a cohort of patients with juvenile idiopathic arthritis: incidence and clinical correlations.

Adalimumab is a TNF-α blocker antibody similar in structure and function to natural human IgG1. Even if adalimumab is fully humanized, the development of anti-drug antibodies has been reported in several inflammatory conditions. The objective of our study was to assess the presence of anti-adalimumab antibodies (AAA) and their clinical relevance in a cohort of juvenile idiopathic arthritis (JIA) patients on adalimumab. This is a prospective observational cohort study recruiting JIA children. Experiments were performed using a validated surface plasmon resonance (SPR)-based optical assay (Biacore® T100). Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score with 10 joint count (JADAS-10). The Mann-Whitney U test, Wilcoxon signed-rank test for paired samples, chi-square, and Fisher exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for entered variables: demographic, clinical, and serological data. Ten (37%) out of 27 patients included in the study had at least one AAA-positive sample. Patients developed AAA between 3 and 38months after starting adalimumab. Seven (70%) out of 10 children with AAA positivity experienced at least a relapse compared to 4 (23.5%) out of 17 AAA-negative children (rs 0.45, p< 0.017). In conclusion, using an innovative and accurate assay method, we found a high incidence of anti-drug antibodies in a cohort of adalimumab-treated JIA patients observed over a mean period of 40weeks; the presence of anti-adalimumab antibodies seemed to be related to the number of relapses.

Adherence to recommendations for the use of anti-tumour necrosis factor and its impact over 5 years of follow-up in axial spondyloarthritis.

To describe adherence to recommendations for TNFα blocker (TNFb) initiation and continuation in early axial Spondyloarthropathy (axSpA); and to evaluate the impact of adherence to these recommendations over 5 years of follow-up in the DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR) cohort. The first 5 years of follow-up of the DESIR early axSpA cohort were analysed. We evaluated adherence to Assessment of SpondyloArthritis International Society (ASAS) 2003/2006, 2016 and European Medicines Agency recommendations in axSpA patients for: TNFb initiation (patients were adherent if they either commenced TNFb therapy when they met the conditions for initiation or if they did not commence TNFb therapy when conditions were not met) and; TNFb continuation (either when they continued TNFb therapy when conditions to continue were met or when they discontinued when conditions were not met). The impact of adherence to these recommendations on functional disability, quality of life and sick-leave days over 5 years was explored. A total of 708 patients were analysed: 440 (62.15%), 389 (54.94%) and 335 (47.32%) were considered adherent to ASAS 2003/2006, 2016 and European Medicines Agency recommendations for TNFb initiation, respectively. Adherence to 2003/2006 and 2016 recommendations for TNFb continuation was observed in 47.37 and 49.39% of patients, respectively. According to over 5 years of follow-up, better outcomes (lower BASFI, higher SF-36 and fewer days of sick leave) were found in patients adhering to recommendations for TNFb commencement and continuation. Less than 50% of patients were treated in agreement with recommendations for TNFb initiation and continuation. Nevertheless, adherence to such recommendations leads to better functional outcomes and fewer days of sick leave, according to long-term follow-up.

Ensuring the Consistency of Biosimilars.

Biological products are subject to constant reappraisal by regulatory agencies and pharmaceutical companies once they have entered the market, since every improvement in their manufacturing process has the potential to alter the basic properties of these molecules. Narrative review focusing on scientific literature as well as legal documents from regulatory agencies. Evaluating the impact of each manufacturing change of these drugs requires rigorous analyses in proportion to the anticipated risk of inducing more or less molecular micro-heterogenicity. There are currently more than 30 biosimilars of TNF-α blockers at different stages of testing, each with a specific manufacturing process. Although the initial demonstration of biosimilarity is now a well-established exercise, it does not guarantee that successive manufacturing changes will not result in a widening gap between drifted/evolved innovators and drifted/evolved biosimilars, as well as among the different biosimilars of a given original biologic. Given the structural complexity of TNF-α blockers-as well as of other biologic drugs included in the armamentarium of systemic inflammatory diseases-regulatory agencies should make available to the practitioner, in a simple and constantly updated way, all available data regarding quality standards of both original molecules and biosimilars. Furthermore, they should strive to guarantee that, once a compound has received approval, it maintains a level of consistency throughout its commercial life in order to maintain and increase confidence in these valuable drugs.

Periodontal Conditions during Arthritis Therapy with TNF-α Blockers

Periodontal Conditions during Arthritis Therapy with TNF-α Blockers

Macrophages in trigeminal ganglion contribute to ectopic mechanical hypersensitivity following inferior alveolar nerve injury in rats

BackgroundAccidental mandibular nerve injury may occur during tooth extraction or implant procedures, causing ectopic orofacial pain. The exact mechanisms underlying ectopic orofacial pain following mandibular nerve injury is still unknown. Here, we investigated the role of macrophages and tumor necrosis factor alpha (TNFα) in the trigeminal ganglion (TG) in ectopic orofacial pain following inferior alveolar nerve transection (IANX).MethodsIANX was performed and the mechanical head-withdrawal threshold (MHWT) in the whisker pad skin ipsilateral to IANX was measured for 15 days. Expression of Iba1 in the TG was examined on day 3 after IANX, and the MHWT in the whisker pad skin ipsilateral to IANX was measured following successive intra-ganglion administration of the macrophage depletion agent liposomal clodronate Clophosome-A (LCCA). TNFα expression in the TG and the MHWT in the whisker pad skin ipsilateral to IANX following successive intra-ganglion administration of the TNFα blocker etanercept were measured on day 3 after IANX, and tumor necrosis factor receptor-1 (TNFR1) immunoreactive (IR) cells in the TG were analyzed immunohistochemically on day 3.ResultsThe MHWT in the whisker pad skin was significantly decreased for 15 days, and the number of Iba1-IR cells was significantly increased in the TG on day 3 after IANX. Successive intra-ganglion administration of the macrophage depletion agent LCCA significantly reduced the increased number of Iba1-IR cells in the TG and reversed the IANX-induced decrease in MHWT in the whisker pad skin. TNFα expression was increased in the TG on day 3 after IANX and was reduced following successive intra-ganglion administration of the TNFα inhibitor etanercept. The decreased MHWT was also recovered by etanercept administration, and TNFR1-IR cells in the TG were increased on day 3 following IANX.ConclusionsThese findings suggest that signaling cascades resulting from the production of TNFα by infiltrated macrophages in the TG contributes to the development of ectopic mechanical allodynia in whisker pad skin following IANX.

Incidence of human cytomegalovirus infection and T-cell response in patients with psoriasis before and during antitumour necrosis factor-α therapy

psoriasis is a chronic inflammatory skin disease that affects approximately 2-3% of the world population.1 Among the cytokines produced by T cells, TNF-α has a crucial role in psoriasis.2 Thus, TNF-α blocking therapy is efficient in the treatment of psoriasis. This article is protected by copyright. All rights reserved.

La inhibición del TNF-α puede disminuir los biomarcadores de disfunción endotelial en pacientes con psoriasis de moderada-grave: un estudio cuasiexperimental eco doppler a 52 semanas

ObjectivesPsoriasis is associated to endothelial dysfunction, which causes impaired vascular functioning. TNF-α blockers have shown the ability to improve vascular functioning in psoriasis. The nailfold vessel resistance index (NVRI) assesses microvascular functioning at nailfold. The objectives of the study is to assess the effect of the TNF-α inhibition with adalimumab on NVRI. Material and methodsQuasi-experimental study. Fifteen patients with moderate-severe psoriasis received adalimumab 40mg sc according to label information. Participants were assessed at baseline and at 12, 24 and 52 weeks after study intervention. ResultsA reduction of −0.09±0.02 (P<.01) in NVRI and a −11.2±2,41ng/ml (P<.001) in E-selectin was observed at week 52. ConclusionsAdalimumab could produce a progressive and sustained reduction of vessel resistance at nailfold and E-selectin in patients with psoriasis.

Sensitization of neuroblastoma for vincristine-induced apoptosis by Smac mimetic LCL161 is attended by G2 cell cycle arrest but is independent of NFκB, RIP1 and TNF-α.

We demonstrated sensitization for chemotherapy by Smac mimetic (SM) LCL161, a potent antagonist of inhibitor of apoptosis proteins (IAP), in neuroblastoma (NB). Vinca alkaloids, particularly vincristine (VCR), displayed the strongest impact on inhibition of proliferation and apoptosis induction in combination with LCL161. The underlying signaling pathways remain elusive, though. LCL161 induces a quick degradation of cellular IAP 1 (cIAP-1). Combination of LCL161 with VCR had only marginal effects on X-linked IAP (XIAP) protein expression. Cell death is accompanied by activation of intrinsic (caspase-9 and MMP) and extrinsic (caspase-8) pathways of apoptosis, repression of migratory potential and cell cycle arrest in G2 phase.LCL161-induced cIAP degradation leads to activation of non-canonical and blockade of canonical NF-κB pathways but not induction of apoptosis. Surprisingly NF-κB and TNF-α signaling is negligible for VCR- and VCR/LCL161-induced apoptosis since chemical inhibition of NF-κB using BAY-7085 and PBS-1086, as well as application of TNF-α blocking antibody Humira (adalimumab) has no relevant effect on cell death. Recently formation of a TNF-α-independent complex (ripoptosome) consisting of RIP1, FADD and caspase-8 following IAP inhibition by SM has been described. However, targeting of RIP1 by Necrostatin was not sufficient to influence apoptosis induced by VCR/LCL161.

Relationship between serum adipokine levels and radiographic progression in patients with ankylosing spondylitis: A preliminary 2-year longitudinal study.

The immunomodulatory effects of adipokines have been extensively studied in rheumatic diseases, and there is a paucity of information regarding their effects on bone metabolism.The aim of this study was to investigate the relationships between serum adipokines levels and radiographic progression over 2 years in patients with ankylosing spondylitis (AS).In this preliminary longitudinal study, we prospectively recruited 20 consecutive male patients with AS and 11 gender- and age-matched healthy subjects. At the baseline and 2-year follow-up, serum adiponectin, leptin, resistin, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Dickkopf-1(DKK-1) levels were measured in AS patients using enzyme-linked immunosorbent assays; these measurements were only performed at the baseline for healthy controls. Radiographic progression was determined as the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) progression of ≥2 by comparing the baseline and 2-year follow-up radiographs.All AS patients were naive to TNF-α blockers at the enrollment and during the 2-year follow-up period and their median disease duration was 51.5 months. At the baseline, the serum resistin, TNF-α, and IL-6 levels were significantly higher in AS patients than in controls. At the 2-year follow-up, the median mSASSS of AS patients was found to be significantly increased from the baseline (8–10.5, P = .001) and 7 (35%) AS patients showed radiographic progression. In AS patients, the leptin and resistin levels were significantly higher at the 2-year follow-up than at the baseline. The baseline resistin levels and changes in leptin levels from the baseline to the 2-year follow-up were significantly higher in AS patients with radiographic progression than in those without radiographic progression (P = .002 and .024, respectively). The baseline resistin levels and the increase in leptin levels during the follow-up period significantly correlated with changes in mSASSS (ρ = 0.528 and 0.559, P = .017 and .01, respectively). No association between changes in serum adipokine levels and disease activity in AS patients was observed.Our findings suggest that leptin and resistin may contribute to the pathogenesis of new bone formation rather than to inflammatory processes and have the potential to be used as biomarkers of the structural outcome of AS.

Fat Mass Lowers the Response to Tumor Necrosis Factor-α Blockers in Patients with Ankylosing Spondylitis

Our main objective was to assess the relationship between body composition (BC) and response to tumor necrosis factor-α (TNF-α) blocker treatment in patients with ankylosing spondylitis (AS). Our secondary objective was to evaluate the change of BC after treatment, accounting for sex and age. All included patients fulfilled the modified New York criteria for AS and were naive to TNF-α blocker. They were followed for at least 6 months after the start of etanercept or adalimumab. The Ankylosing Spondylitis Disease Activity Score containing C-reactive protein (ASDAS-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were reported. BC was assessed by whole body dual-energy X-ray absorptiometry. Body fat percentage (BF%), fat mass index (FMI), and fat free mass index (FFMI) were reported as absolute values and as percentiles. Forty-one patients were included (61% men). The median followup was 14.3 months (interquartile range 8.4-19.4). After multivariate regression analysis, more fat at baseline (BF%, FMI, or FMI percentile) was significantly related with a lower chance of achieving a clinically important improvement of the ASDAS-CRP or BASDAI after treatment. The body composition did not change significantly after treatment, but there was a trend toward muscle recovery in men (FFMI change from 34.0th to 37.4th percentile). Higher body fat content at baseline was independently associated with a worse response to treatment with TNF-α blockers, measured by ASDAS-CRP and BASDAI change, and might contribute to the lower response rates in female patients. Also, there is a trend toward muscle mass recovery in male patients after treatment.

TNFα blockers followed by continuation of sulfasalazine and methotrexate combination: a retrospective study on cost saving options of treatment in Spondyloarthritis.

High cost deters continuous use of tumor necrosis factor α blockers (TNFi) in developing countries. The objective of this study was to evaluate outcome and expenditure incurred in Spondyloarthritis (SpA) patients beyond a year of follow-up after receiving four doses of infliximab (IFX) over and above background therapy of methotrexate (MTX) and sulfasalazine (SSZ)combination. Electronic medical records were screened for patients with SpA satisfying the Assessment of Spondyloarthritis International Society (ASAS) criteria between 2008 and 2014. Patients who completed at least 1year of follow-up after receiving four doses of IFX (5mg/kg at 0, 2, 6, and 14weeks) on a background therapy of MTX (10-25mg/week) and SSZ (2-3g/day) combination were enrolled after obtaining an informed consent. Primary outcome assessed was "time to disease flare". Changes in acute phase reactants, patient reported outcomes (BASDAI, BASFI), and cost were also assessed. Forty-five patients were enrolled. Mean (SD) duration of follow up after fourth IFX dose was 28.9 (18.7) months. Disease flare occurred in 33.3% (15/45) after a mean (SD) duration of 14.5 (10.8) months as compared to 4-6months described in literature on discontinuing TNFi. Reduction in ESR, CRP, BASDAI and BASFI continued to be statistically significant at follow-up as compared to baseline. As compared to continuous IFX therapy, this treatment reduced cost by 57.1% for each patient-month of follow-up. Short course IFX dosing followed by continuation of MTX and SSZ combination can prolong time to disease flare and decrease requirement for additional IFX dose in SpA. This regimen could be a cost saving option for patients with SpA.