Mediators of Inflammation

Mediators of Inflammation / 2014 / Article
Special Issue

Targeting TNF and Its Family Members in Autoimmune/Inflammatory Disease

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Review Article | Open Access

Volume 2014 |Article ID 493593 |

Pierre-André Jarrot, Gilles Kaplanski, "Anti-TNF-Alpha Therapy and Systemic Vasculitis", Mediators of Inflammation, vol. 2014, Article ID 493593, 9 pages, 2014.

Anti-TNF-Alpha Therapy and Systemic Vasculitis

Academic Editor: Sophie Desplat-Jégo
Received28 Jun 2013
Revised07 Jan 2014
Accepted16 Jan 2014
Published27 Feb 2014


TNF-α is a pleiotropic cytokine, which plays a major role in the pathogenesis of numerous autoimmune and/or inflammatory systemic diseases. Systemic vasculitis constitutes a group of rare diseases, characterized by inflammation of the arterial or venous vessel wall, causing stenosis and thrombosis. Treatment of the different type of vasculitis mainly relies on steroids and immunosuppressive drugs. In case of refractory or relapsing diseases, however, a second line of treatment may be required. Anti-TNF-α drugs have been used in this setting during the last 15 years with inconsistent results. We reviewed herein the use of anti-TNF-α therapy in different kind of vasculitis and concluded that, except for Behcet’s disease, this therapeutic option has not demonstrated significant improvement in the treatment of vasculitis.

1. Introduction

Tumour necrosis factor alpha (TNF-) is a pleiotropic cytokine known to play a major role in host defense mechanisms, initiating a beneficial local inflammation which in excess, however, may cause tissue damage [1]. Since 1999, anti-TNF- therapy has been used with success in the treatment of patients suffering from rheumatoid arthritis (RA), inflammatory enterocolitis (Crohn’s disease and ulcerative colitis), spondyloarthropathies, or psoriasis [26]. Randomized international studies have shown the efficacy of five currently commercially available anti-TNF- molecules. These molecules have also been tested in other autoimmune and inflammatory systemic diseases such as severe vasculitis refractory to conventional treatment but, to date, vasculitis are not included in the list of therapeutic indications of anti-TNF- agents.

Systemic vasculitis is a group of rare diseases characterized by inflammation of the arterial or venous vessel wall, causing stenosis or thrombosis [7]. Initially classified by the size of the vessel involved, primitive vasculitis has been recently reclassified with the introduction of immunological markers in the new Chapel Hill Consensus classification [8]. One can distinguish between large vessels vasculitis (giant cell arteritis (GCA) and Takayasu arteritis (TA)), medium vessels vasculitis (periarteritis nodosa (PAN)), and small vessels vasculitis with immune complex deposits (mixed cryoglobulinemia (MC)) or associated with anti-neutrophil cytoplasmic antibodies (ANCA) (granulomatosis with polyangeitis (GPA) formerly Wegener granulomatosis, eosinophilic granulomatosis with polyangeitis (EGPA) formerly Churg-Strauss disease, and micropolyangeitis (MPA)). In addition, some diseases may affect vessels of variable size (Behcet disease (BD)) [8]. We reviewed the published experience related to the use of anti-TNF- therapy in these diseases, pointing to the fact that data are relatively rare and often contradictory.

2. Rationale for the Use of Anti-TNF- in Vasculitis?

Two forms of TNF- are synthesized by activated macrophages and dendritic cells: a transmembrane precursor form (26 Kda) which is proteolytically cleaved in a soluble form (17 kda) by a TNF- converting enzyme (TACE) [9]. These two forms bind to two ubiquitous cell surface receptors (TNFR1 and TNFR2) on target cells to initiate proinflammatory genes transcription via the activation of Nuclear Factor Kappa B (NFκB) and Mitogen Activated Protein (MAP) Kinase pathways, as well as proapoptotic genes transcription by the induction of death signal pathways [1, 10]. TNF- induces leukoendothelial adhesion via increased expression of various adhesion molecules, such as E-selectin, Intercellular Adhesion Molecule 1 (ICAM-1), and Vascular Adhesion Molecule 1 (VCAM-1), and mediates tissue leukocyte infiltration through chemokine synthesis [11]. TNF- induces metalloproteinase production and may also participate in endothelial cell death directly via apoptosis or indirectly via neutrophil activation [10].

In addition, TNF- may play a role in neutrophil “priming” inducing membrane expression of proteinase-3 or myeloperoxidase, which are subsequently recognized by ANCA in ANCA-associated vasculitis (AAV) [12]. This cytokine may thus be involved in the pathogenesis of different kind of vasculitis. In addition, binding of anti-TNF- to membrane-associated TNF- can have an agonistic action, initiating reverse signaling and processes such as apoptosis, cytokine suppression, and cell activation, which could constitute an interesting target in the treatment of vasculitis [11, 13]. To date, 5 different anti-TNF- drugs have been developed and are commercially available, 3 consisting in monoclonal antibodies (infliximab (IFX), adalimumab (ADA), and golimumab). IFX is usually used intravenously at 3 to 5 mg/kg every 8 weeks, and ADA and golimumab are used subcutaneously, 40 mg every 2 weeks for the former and 50 mg once a month for the latter. The fourth available drug is a dimer of a chimeric protein genetically engineered by fusing the extracellular ligand binding domain of human tumour necrosis factor receptor 2 (TNFR2/p75) to the Fc domain of human IgG-1 (etanercept (ETN)) and is used subcutaneously at 25 mg twice a week. The last is a humanised Fab fragment conjugated to polyethylene glycol (certolizumab pegol) but has never been used in vasculitis. Monoclonal antibodies and certolizumab are active on the two molecular forms of TNF, whereas etanercept neutralizes soluble TNF- only.

3. Large Vessels Vasculitis

3.1. Giant Cell Arteritis (GCA)

The pathogenesis of GCA seems due to an abnormal cell-mediated immune response taking place in the vessel wall, leading to macrophage activation, giant cell formation, and excess production of interferon gamma [14]. Other proinflammatory cytokines such as IL-1, IL-6, and IL-17 may be involved in GCA pathogenesis, whereas experimental data showing the role of TNF- in this disease are sparse [15]. GCA mostly affects people older than 50 years. Long-term corticosteroids remain the main treatment which is unfortunately commonly complicated by many side effects [16]. Immunosuppressive drugs such as methotrexate (MTX) or aziatropine (AZT) have been used in order to have a steroid sparing effect and in some corticodependent/resistant patients. MTX was tested in 3 prospective studies with contradictory effects, and AZT gave disappointing results in a controlled study enrolling 31 patients [1720]. Thus, after a few cases showing successful anti-TNF- treatment in corticodependent GCA patients have been reported, a comparative double blind study was conducted using IFX but was subsequently stopped due to the lack of efficacy on the prevention of relapse [21]. Regarding ETN, a randomized controlled study against placebo was conducted on 17 patients and demonstrated a significant corticosteroid sparing effect after one year, but not for a longer period which was nevertheless the primary end point [22]. Finally, ADA showed no benefit in a prospective study including 70 patients with a primary end point of steroid sparing at week 26 [23]. In view of these different studies, anti-TNF- therapy is not recommended in GCA (Table 1).

ReferencesDesign/anti-TNF-α therapyNumber of patientsMain objectivesFollow-upMain resultsSide effects

Hoffman et al. [21]Randomized controlled trial IFX versus placebo44 (28 IFX, 16 placebo)Free of relapses and adverse events at 54 weeks54 weeksStopped early at week 22 for lack of efficacy (43% for IFX versus 50% for placebo)Infection: 71% for IFX versus 56% for placebo (NS)

Martínez-Taboada et al. [22]Randomized controlled trial ETN versus placebo17 (8 ETN, 9 placebo)To withdraw the corticosteroid therapy at 12 months12 months50% for ETN versus 22% for placebo (NS)No differences between the two groups

Mariette et al. [23]Randomized controlled trial ADA versus placebo70 (34 ADA, 36 placebo)Remission and corticosteroid < 0,1 mg/kg/day at 26 weeks26 weeks55,9% for ADA 50% for placebo (NS)Severe infections: 8,8% for ADA versus 13,9% for placebo (NS)

ns: nonsignificant.
3.2. Takayasu Arteritis (TA)

TA is characterized by inflammation of large vessels, primarily the aorta and its main branches, resulting in anevrysm formation, vascular stenosis, or occlusion, affecting mainly young women. TA is a chronic idiopathic granulomatous panarteritis, resulting from infiltration of the three layers of the vessel wall by macrophages, T lymphocytes, and natural killer cells [14, 24]. First line treatment consists in high doses of corticosteroids [24]. However, almost 50% of TA patients demonstrate glucocorticoid resistance or relapsing disease, requiring the addition of immunosuppressive agents such as AZT, cyclophosphamide (CYC), or mycophenolate mofetil (MMF) with inconsistent efficiency [25]. To date, approximately 120 TA patients have been treated with anti-TNF-, mostly with IFX, as a second/third line immunosuppressive therapy. A first open label prospective study involving 15 patients with active or relapsing disease (8 treated by infliximab and 7 by etanercept) suggested some therapeutic efficacy which was confirmed by other studies (90% rate of remission and 60% for sustained remission) [2628] (Table 2). Relapses, however, seem to be common after the drug is stopped following remission [27]. In summary, despite the fact that no prospective controlled study has been conducted to date, anti-TNF- may constitute an interesting therapeutic option in TA patients who have been unable to achieve or maintain remission with steroids alone or common immunosuppressive agents.

ReferencesDesign/anti-TNF-α therapyNumber of patientsMain objectivesFollow-upMain resultsSide effects

Hoffman et al. [26]Open label trial IFX/ETN15Remission and discontinuation of corticosteroids12 months67% complete remission 27% partial remission (50% of glucocorticoid requirements reduction)One infusion reaction to IFX

4. Medium Size Vessels Vasculitis

4.1. Periarteritis Nodosa (PAN)

PAN is a rare necrotizing vasculitis complicating hepatitis B virus chronic carriage affecting medium size vessels, whose incidence has declined since the introduction of hepatitis B vaccination and antiviral treatments [29]. The treatment of PAN consists in steroids or immunosuppressive drugs in association with antiviral therapy, according to the gravity of the disease [29, 30]. In a few case reports, IFX has been used in refractory forms of the disease or because of intolerance of conventional drugs and seems to be effective [31].

5. Small Size Vessels Vasculitis

5.1. Mixed Cryoglobulinemia (MC)

MC is a small vessel vasculitis involving skin, joints, peripheral nerves, and the kidney, which is mainly associated with hepatitis C, Sjogren’s syndrome, or lymphoma [32]. MC is a model of immune-complex-mediated inflammation of blood vessels and may involve TNF- [33]. Before the area of anti-CD-20-targeted biotherapy, only 3 patients with refractory hepatitis C-associated MC treated with anti-TNF- have been reported with conflicting results, some patients even experiencing severe flare-up of the disease [34, 35]. At present, the treatment of MC relies on plasma exchange, immunosuppressive drugs, antivirals, and anti-CD-20 therapy (rituximab) [36].

5.2. ANCA-Associated Vasculitis (AAV)

AAV is a group of multisystemic diseases characterized by a pauci-immune small vessel vasculitis which includes three different entities: two recently renamed granulomatosis with polyangeitis (GPA), eosinophilic GPA (EGPA), and microscopic polyangeitis (MPA). AAV pathogenesis is consistent with a primary role for neutrophils, which are both the effector cells responsible for endothelial damage via oxygen radical synthesis and enzyme degranulation and the targets of ANCA [37]. Current AAV treatment is based on a six-month induction phase associating high-dose steroids with immunosuppressive drugs such as CYC or rituximab, followed by an 18-month maintenance therapy with AZT [38]. However, using these standard treatment protocols, relapses are very common, occurring in 49% and 35% of patients with GPA and MPA, respectively [29, 39]. Moreover, some patients remain refractory to conventional treatments, raising the need for new therapeutic options.

Etanercept was tested initially in an open label trial including 20 relapsing or incompletely controlled GPA and seemed efficient with a 3-point reduction of the Birmingham Vasculitis activating (BVAS) score at 6 months [40]. These results were not confirmed in a larger controlled prospective study including 180 GPA patients [41]. However, it should be noted that this latter study had some design limitations since the two groups were not homogeneous at the baseline, and some patients had localized forms of the disease. Finally, although ETN is known to be of little usefulness in granulomatous disease, only the WGET study provides data confirming that the addition of ETN to usual treatments is ineffective in the maintenance regimen of GPA [41]. Anti-TNF- monoclonal antibodies have also been tested in refractory AAV patients. The efficiency of infliximab has been observed in prospective observational studies [42, 43]. One multicentric prospective randomized control trial involving 17 patients compared the efficacy of infliximab () or rituximab () in association with steroids and immunosuppressive drugs in refractory GPA for a median follow-up of 30.6 months (+/−15.4). Efficacy of infliximab and/or rituximab to obtain remission at one year was observed, with an advantage for rituximab. During long-term follow-up, rituximab was also more effective at obtaining and maintaining remission [44]. Recently, 33 patients with active AAV (BVAS > 10) were enrolled in an open prospective trial to study infliximab adjunction to standard therapy in order to obtain remission for a median follow-up of 12 months and demonstrated no benefit with anti-TNF-. However, this was a noncontrolled study and groups lacked homogeneity [45]. The last open label prospective study was conducted with adalimumab associated with standard therapy in refractory AAV with renal involvement. Although no significant gain in response rate was observed, a significant steroid sparing effect was noted [46].

In conclusion, it seems that a short course anti-TNF- therapy using infliximab may be useful in complement to standard regimen in some refractory AAV patients, but the recent published data on the beneficial effects of rituximab for obtaining remission and preventing relapses in MPA and GPA appear much more convincing and may significantly limit the use of anti-TNF- treatment in AAV in the future [47, 48] (Table 3).

ReferencesDesign/anti-TNF-α therapyNumber of patientsMain objectivesFollow-upMain resultsSide effects

Stone et al. [40]Open label trial ETN20 GPABVAS at 6 months adverse events during 6 months6 months3 points Decrease of BVAS (P < 0,05)Injection site reaction in 25%
95% of patients still taking ETN

WGET research group [41]Randomized controlled
ETN versus placebo
180 GPA
(89 ETN, 91 placebo)
Sustained remission at 27 months
(BVAS = 0)
27 months69,7% for ETN
versus 75,3% for placebo (NS)
56,2% for ETN versus 57,1% for placebo had a life threatening event (NS)

Morgan et al.
Open label
trial IFX
33 (22 GPA, 11 MPA)
(16 IFX, 17 standard treatment)
Time to clinical remission (BVAS ≤ 1)12 monthsNo difference between the two groupsInfections in 8 patients for IFX and 7 for standard treatment (NS)

De Menthon et al. [44]Randomized controlled trial
IFX versus rituximab
17 GPA
(9 IFX, 8 RTX)
at month 12
12 monthsIFX: 2 CR, 1 PR
RTX: 4 CR, 1 PR
One death in
both groups
(invasive Aspergillosis for IFX and sudden death for RTX)

Laurino et al.
Phase 2
open label
trial ADA
14 (9 GPA,
5 MPA)
(i) Induction of remission within the first 14 weeks
(ii) time to remission
17 months(i) 78,5% achieved remission
(ii) Time to remission 12 weeks
Infections in 3 patients (1 mild and 2 severe including 1 death)

NS: Nonsignificant; RTX: rituximab; CP: complete remission; PR: partial remission.

6. Variable Size Vessels Vasculitis

6.1. Behcet’s Disease (BD)

BD is a chronic and relapsing systemic inflammatory disorder characterized by recurrent orogenital ulcerations with possible mucocutaneous, ocular, digestive, vascular, and/or central nervous system involvements. BD pathogenesis is still unclear, but an association between genetic intrinsic factors (HLA-B5) and triggering extrinsic factors is suspected [49, 50]. First line treatments are adapted to each organ involvement, such as colchicine for mucocutaneous symptoms or combination of steroids and immunosuppressive drugs in case of severe visceral involvement [51]. Some patients however may develop severe and even life-threatening complications despite these standard treatments regimens. The pathogenic role of TNF- in mediating tissue injury during BD seems to be major, and increased levels of TNF- and soluble TNF receptors have been found in the peripheral blood of patients with active BD [52, 53].

In 2001, anti-TNF- treatments were first tested for severe eye involvement showing promising results [54]. A meta-analysis collecting 158 patients included in 14 prospective studies testing infliximab in BD with ocular lesions refractory to immunosuppressive drugs was realized in 2011. A complete or partial remission was achieved in 65% and 24% of patients receiving infliximab, allowing glucocorticoids and immunosuppressive release in about 40% [55]. A recent open label prospective study enrolling 63 patients receiving infliximab showed similar results after one year of treatment [56]. Interestingly, the improvement was rapidly obtained following the initiation of infliximab [57].

Five open prospective studies demonstrated a beneficial effect of long-term infliximab treatment on the prevention of relapse, maintenance of visual acuity, and immunosuppressive drugs tapering [5761] (Table 4). Intravitreous injection of infliximab was also tested in refractory uveitis in 15 patients and demonstrated a positive effect [62]. Regarding the use of adalimumab, etanercept, and golimumab, only case reports are currently available but showed beneficial effects in refractory uveitis, [6365].

ReferencesDesign/anti-TNF-α therapyNumber of patientsMain objectivesFollow-upMain resultsSide effects

Okada et al. [56]Open label trial IFX63Efficacy of IFX in the first year of treatment12 monthsImprovement in 69% Improvement somewhat in 23%
Unchanged in 8%
46% of side effects including 3 infusion reactions
No serious side effects

Sfikakis et al. [57]Open label trial IFX25Remission at day 2828 days89% of complete remissionNo serious side effects

Ohno et al. [58]Open label trial IFX12Frequency of ocular attacks14 weeksReduction in the number of relapses for IFX (5 mg/kg and 10 mg/kg)One case of tuberculosis (IFX 10 mg/kg)

Accorinti et al. [59]Open label trial IFX12Frequency of ocular attacks15 months91% of reduction in the number of relapses33% of side effects including one tuberculosis and one herpetic keratitis

Tognon et al. [60]Open label trial IFX7Frequency of ocular attacks23 months21 to 6 ocular attacks observed in the equivalent period of time before treatmentOne infusion reaction

Tugal-Tutkun et al. [61]Open label trial IFX13Absence of ocular attacks6 years31% remained attack-free 32 to 13 ocular attacks observed in the equivalent period of time before treatmentNo serious side effects (7 respiratory tract infection and one infusion reaction)

Anti-TNF- treatments were tested in severe refractory cutaneous manifestations, especially etanercept which revealed a significant efficacy compared to placebo on oral ulcers, and nodular lesions [66].

Infliximab in monotherapy was also tested in refractory entero-Behcet during a prospective open trial and showed 100% improvement on clinical, CT-scan, and colonoscopy [67]. Adalimumab may also be efficient in this kind of patients [68].

In addition, infliximab has been used in BD affecting the central nervous system (CNS) in open prospective studies and was almost always successful [69, 70]. These patients were refractory to high-dose steroids combined with various immunosuppressive drugs and demonstrated major improvement or stabilization of their symptoms. Long-term remission (6–18 months) after discontinuation of infliximab therapy was noted in 75% of patients [69, 70] (Table 5). Adalimumab and etanercept have also been tried in case reports of BD with CNS involvement with a favorable outcome [71, 72]. In case of a first anti-TNF- failure in refractory BD, a switch of molecule was made in up to 25% of cases with a 70% improvement [73].

ReferencesType of involvement/design/anti-TNF-α therapyNumber of patientsMain objectivesFollow-upMain resultsSide effects

Melikoglu et al. [66]Cutaneous/randomized controlled trial/ETN versus placebo40 (20 ETN/20 placebo)(i) Pathergy response and monourate sodium status
(ii) frequencies of mucocutaneous manifestations
4 weeks(i) No differences between the two groups
(ii) decrease of frequency of mucocutaneous manifestations
No serious side effects

Iwata et al. [67]Entero-Behcet/open label trial/IFX10Clinical manifestations CT-scan12 monthsRapid and dramatic improvement for all the patientsNo serious side effects

Kikuchi et al. [69]Neuro-Behcet/open label trial/IFX5Clinical manifestations brain magnetic resonance imaging24 weeksImprovement in 3 patientsOne pneumocystis pneumonia

Giardina et al. [70]Neuro-Behcet/open label trial/IFX21Clinical manifestations (CR/PR)54 weeks85% of CR 9% of PRNo serious side effects

CR: complete remission; PR: partial remission.

In summary, infliximab seems effective in induction treatment and relapse prevention in severe BD refractory to glucocorticoids or immunosuppressive drugs, especially in case of eye involvement. It could also be an alternative therapy to immunosuppressive drugs in case of central nervous system or gastrointestinal manifestations. Nevertheless, the main limitation of the present analysis is that most information originated from limited cases or noncontrolled studies, strongly raising the need for properly randomized controlled clinical trials.

7. Safety and Tolerance of TNF-Alpha Blockade

In vasculitis, anti-TNF- are often prescribed as second/third line treatments in patients already immunocompromised by long-term use of glucocorticoids and immunosuppressive drugs. Despite this fact, side effects have been reported up to 46% and are mostly moderate. The literature review suggests that these drugs are rather safe, in agreement with what is known in RA and spondyloarthropathy [56, 74].

Patients treated with anti-TNF- are prone to develop soon after initiation bacterial and viral infections mostly affecting respiratory or urinary tracts and cutaneous or soft tissues. Furthermore, reactivation of latent tuberculosis or extrapulmonary forms of this infection is another well-known threat [7581].

The role of anti-TNF- therapy in carcinogenesis and tumor progression remains a matter of controversy. A large study assessed the risk of cancer in a RA cohort treated with anti-TNF- and showed a relative risk (RR) of 1.00 (95% CI: 0.86–1.15) compared to the biotherapy naïve RA cohort. RR did not increase with longer exposure or with the cumulative duration of active anti-TNF- therapy during a 6-year follow-up period [82]. Regarding the risk of hemopathy, infliximab and etanercept were not associated with the occurrence of lymphoma in a study involving 19,000 patients with RA [83]. One observational study, however, showed a positive association between anti-TNF- therapy in RA and nonmelanoma skin cancers with a follow-up period of 3 years [84]. In vasculitis, especially AAV, an unusually high frequency of solid cancer was reported in a randomized controlled trial that evaluated etanercept for maintenance of remission in 180 patients with GPA. But all the patients () who developed cancer also received standard therapy associating MTX or CYC, which are known to be involved in cancerogenesis [44]. Without large specific epidemiological studies, caution is however advised.

Besides infection and malignancy, anti-TNF- treatments can induce acute infusion reaction, which may lead to discontinuation of the treatment. Anti-TNF therapy may also favor antinuclear antibodies appearance which are, however, weakly associated with clinical symptoms [85, 86]. Other extending complications are allocated to anti-TNF- treatments, such as the occurrence of demyelinating and sarcoid-like granulomatous diseases [87].

8. Conclusion

Anti-TNF- treatments in vasculitis did not demonstrate the same efficacy as in other inflammatory diseases such as RA. Nevertheless, anti-TNF- should be used in the treatment of BD refractory to immunosuppressive drugs, especially in case of ocular, CNS, or digestive tract involvement. Some interesting data are also available for the use of anti-TNF- treatments in refractory AAV, but the recent reports on rituximab efficacy in these diseases and the relative innocuity of this drug may limit the use of anti-TNF- in these diseases, in the future. In both BD and AAV, an anti-TNF monoclonal antibody especially infliximab should be preferred to etanercept. In addition, physicians must be aware of the risk of infection using these drugs, especially in patients already immunocompromised by previous treatments. Regarding other vasculitis, published data are not in favor of efficiency of anti-TNF- which, therefore, should not be used.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.


  1. D. Tracey, L. Klareskog, E. H. Sasso, J. G. Salfeld, and P. P. Tak, “Tumor necrosis factor antagonist mechanisms of action: a comprehensive review,” Pharmacology & Therapeutics, vol. 117, no. 2, pp. 244–279, 2008. View at: Publisher Site | Google Scholar
  2. D. H. Present, P. Rutgeerts, S. Targan et al., “Infliximab for the treatment of fistulas in patients with Crohn's disease,” The New England Journal of Medicine, vol. 340, no. 18, pp. 1398–1405, 1999. View at: Publisher Site | Google Scholar
  3. P. Rutgeerts, W. J. Sandborn, B. G. Feagan et al., “Infliximab for induction and maintenance therapy for ulcerative colitis,” The New England Journal of Medicine, vol. 353, no. 23, pp. 2462–2476, 2005. View at: Publisher Site | Google Scholar
  4. M. A. Dentener and E. F. M. Wouters, “Tumor necrosis factor inhibitors for rheumatoid arthritis,” The New England Journal of Medicine, vol. 355, no. 19, pp. 2047–2048, 2006. View at: Google Scholar
  5. S. Schnarr, J. G. Kuipers, and H. Zeidier, “Anti tumour necrosis factor (TNF-alpha) in undiferenciated spondyloarthropathy,” Clinical Experimental Rheumatology, vol. 6, no. 20, supplement 28, pp. 126–129, 2002. View at: Google Scholar
  6. U. Chaudhari, P. Romano, L. D. Mulcahy, L. T. Dooley, D. G. Baker, and A. B. Gottlieb, “Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial,” The Lancet, vol. 357, no. 9271, pp. 1842–1847, 2001. View at: Publisher Site | Google Scholar
  7. L. Guillevin, C. Pagnoux, and P. Guilpain, “Classification of systemic vasculatides,” Presse Médicale, vol. 36, no. 5, part 2, pp. 845–853, 2007. View at: Publisher Site | Google Scholar
  8. R. Abdulkader, S. E. Lane, D. G. Scott, and R. A. Watts, “Classification of vasculitis : EMA classification using CHCC 2012 definitions,” Annals of the Rheumatic Diseases, vol. 72, no. 11, article 1888, 2013. View at: Publisher Site | Google Scholar
  9. A. J. H. Gearing, P. Beckett, M. Christodoulou et al., “Processing of tumour necrosis factor-α precursor by metalloproteinases,” Nature, vol. 370, no. 6490, pp. 555–557, 1994. View at: Publisher Site | Google Scholar
  10. M. Aringer and J. S. Smolen, “SLE-complex cytokine effects in a complex autoimmune disease: tumor necrosis factor in systemic lupus erythematosus,” Arthritis Research and Therapy, vol. 5, no. 4, pp. 172–177, 2003. View at: Google Scholar
  11. F. Mackay, H. Loetscher, D. Stueber, G. Gehr, and W. Lesslauer, “Tumor necrosis factor α (TNF-α)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF- R55,” The Journal of Experimental Medicine, vol. 177, no. 5, pp. 1277–1286, 1993. View at: Google Scholar
  12. D. J. Radford, J. M. Lord, and C. O. S. Savage, “The activation of the neutrophil respiratory burst by anti-neutrophil cytoplasm autoantibody (ANCA) from patients with systemic vasculitis requires tyrosine kinases and protein kinase C activation,” Clinical and Experimental Immunology, vol. 118, no. 1, pp. 171–179, 1999. View at: Publisher Site | Google Scholar
  13. H. Mitoma, T. Horiuchi, H. Tsukamoto et al., “Mechanisms for cytotoxic effects of anti-tumor necrosis factor agents on transmembrane tumor necrosis factor α-expressing cells: comparison among infliximab, etanercept, and adalimumab,” Arthritis & Rheumatism, vol. 58, no. 5, pp. 1248–1257, 2008. View at: Publisher Site | Google Scholar
  14. C. M. Weyand and J. J. Goronzy, “Medium- and large-vessel vasculitis,” The New England Journal of Medicine, vol. 349, no. 2, pp. 160–169, 2003. View at: Publisher Site | Google Scholar
  15. S. Visvanathan, M. U. Rahman, G. S. Hoffman et al., “Tissue and serum markers of inflammation during the follow-up of patients with giant-cell arteritis–a prospective longitudinal study,” Rheumatology, vol. 50, no. 11, pp. 2061–2070, 2011. View at: Google Scholar
  16. G. G. Hunder, “Epidemiology of giant-cell arteritis,” Cleveland Clinic Journal of Medicine, vol. 69, supplement 2, pp. SII79–SII82, 2002. View at: Google Scholar
  17. J. A. Jover, C. Hernández-García, I. C. Morado, E. Vargas, A. Bañares, and B. Fernàndez-Gutiérrez, “Combined treatment of giant-cell arteritis with methotrexate and prednisone: a randomized, double-blind, placebo-controlled trial,” Annals of Internal Medicine, vol. 134, no. 2, pp. 106–114, 2001. View at: Google Scholar
  18. R. F. Spiera, H. J. Mitnick, M. Kupersmith et al., “A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis (GCA),” Clinical and Experimental Rheumatology, vol. 19, no. 5, pp. 495–501, 2001. View at: Google Scholar
  19. G. S. Hoffman, M. C. Cid, D. B. Hellmann et al., “A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis,” Arthritis & Rheumatism, vol. 46, no. 5, pp. 1309–1318, 2002. View at: Publisher Site | Google Scholar
  20. M. de Silva and B. L. Hazleman, “Azathioprine in giant cell arteritis/polymyalgia rheumatica: a double-blind study,” Annals of the Rheumatic Diseases, vol. 45, no. 2, pp. 136–138, 1986. View at: Google Scholar
  21. G. S. Hoffman, M. C. Cid, K. E. Rendt-Zagar et al., “Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis a randomized trial,” Annals of Internal Medicine, vol. 146, no. 9, pp. 621–630, 2007. View at: Google Scholar
  22. V. M. Martínez-Taboada, V. Rodríguez-Valverde, L. Carreño et al., “A double-blind placebo controlled trial of etanercept in patients with giant cell arteritis and corticosteroid side effects,” Annals of the Rheumatic Diseases, vol. 67, no. 5, pp. 625–630, 2008. View at: Publisher Site | Google Scholar
  23. X. Mariette, E. Hachulla, C. Larroche et al., “Results of randomized controlled study of adalimumab for steroid sparing in patient with giant cell arteritis and corticosteroid side effects,” Arthritis & Rheumatism, vol. 63, p. S589, 2011. View at: Google Scholar
  24. G. S. Kerr, C. W. Hallahan, J. Giordano et al., “Takayasu arteritis,” Annals of Internal Medicine, vol. 120, no. 11, pp. 919–929, 1994. View at: Google Scholar
  25. G. S. Hoffman, “Treatment of resistant Takayasu's arteritis,” Rheumatic Disease Clinics of North America, vol. 21, no. 1, pp. 73–80, 1995. View at: Google Scholar
  26. G. S. Hoffman, P. A. Merkel, R. D. Brasington, D. J. Lenschow, and P. Liang, “Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis,” Arthritis & Rheumatism, vol. 50, no. 7, pp. 2296–2304, 2004. View at: Publisher Site | Google Scholar
  27. E. S. Molloy, C. A. Langford, T. M. Clark, C. E. Gota, and G. S. Hoffman, “Anti-tumour necrosis factor therapy in patients with refractory Takayasu arteritis: long-term follow-up,” Annals of the Rheumatic Diseases, vol. 67, no. 11, pp. 1567–1569, 2008. View at: Publisher Site | Google Scholar
  28. J. Schmidt, T. A. Kermani, A. K. Bacani, C. S. Crowson, E .L. Matteson, and K. J. Warrington, “Tumor necrosis factor inhibitors in patients with Takayasu arteritis: experience from a referral center with long-term followup,” Arthritis Care Research, vol. 64, no. 7, pp. 1079–1083, 2012. View at: Google Scholar
  29. M. Gayraud, L. Guillevin, P. le Toumelin et al., “Long term follow up of polyarteritis nodosa, microscopic polyangiitis and Churg-Strauss syndrome : analysis of four prospective trials including 278 patients,” Arthritis & Rheumatism, vol. 44, no. 3, pp. 666–675, 2001. View at: Google Scholar
  30. L. Guillevin, A. Mahr, P. Callard et al., “Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients,” Medicine, vol. 84, no. 5, pp. 313–322, 2005. View at: Publisher Site | Google Scholar
  31. K. Wu and D. Throssell, “A new treatment for polyarteritis nodosa,” Nephrology Dialysis Transplantation, vol. 21, no. 6, pp. 1710–1712, 2006. View at: Publisher Site | Google Scholar
  32. O. Trejo, M. Ramos-Casals, M. García-Carrasco et al., “Cryoglobulinemia: study of etiologic factors and clinical and immunologic features in 443 patients from a single center,” Medicine, vol. 80, no. 4, pp. 252–262, 2001. View at: Publisher Site | Google Scholar
  33. G. Kaplanski, V. Marin, T. Maisonobe et al., “Increased soluble p55 and p75 tumour necrosis factor-α receptors in patients with hepatitis C-associated mixed cryoglobulinaemia,” Clinical and Experimental Immunology, vol. 127, no. 1, pp. 123–130, 2002. View at: Publisher Site | Google Scholar
  34. P. Bartolucci, J. Ramanoelina, P. Cohen et al., “Efficacy of the anti-TNF-α antibody infliximab against refractory systemic vasculitidis: an open pilot study on 10 patients,” Rheumatology, vol. 41, no. 10, pp. 1126–1132, 2002. View at: Google Scholar
  35. M.-O. Chandesris, S. Gayet, N. Schleinitz, B. Doudier, J.-R. Harlé, and G. Kaplanski, “Infliximab in the treatment of refractory vasculitis secondary to heptitis C-associated mixed cryoglobulinaemia,” Rheumatology, vol. 43, no. 4, pp. 532–533, 2004. View at: Publisher Site | Google Scholar
  36. B. Terrier and P. Cacoub, “Cryoglobulinemia vasculitis: an update,” Current Opinion in Rheumatology, vol. 25, no. 1, pp. 10–18, 2013. View at: Google Scholar
  37. V. C. Primo, S. Marusic, C. C. Franklin et al., “Anti-PR3 immune responses induce segmental and necrotizing glomerulonephritis,” Clinical and Experimental Immunology, vol. 159, no. 3, pp. 327–337, 2010. View at: Publisher Site | Google Scholar
  38. L. Guillevin, “How to treat systemic necrotizing vasculitides?” Presse Médicale, vol. 41, no. 10, pp. 1024–1030, 2012. View at: Google Scholar
  39. G. S. Hoffman, G. S. Kerr, R. Y. Leavitt et al., “Wegener granulomatosis: an analysis of 158 patients,” Annals of Internal Medicine, vol. 116, no. 6, pp. 488–498, 1992. View at: Google Scholar
  40. J. H. Stone, M. L. Uhlfelder, D. B. Hellmann, S. Crook, N. M. Bedocs, and G. S. Hoffman, “Etanercept combined with conventional treatment in Wegener’s granulomatosis : a six-month open-label trial to evaluate safety,” Arthritis & Rheumatism, vol. 44, no. 5, pp. 1149–1154, 2001. View at: Google Scholar
  41. Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group, “Etanercept plus standard therapy for Wegener's granulomatosis,” The New England Journal of Medicine, vol. 352, no. 4, pp. 351–361, 2005. View at: Publisher Site | Google Scholar
  42. P. Lamprecht, J. Voswinkel, T. Lilienthal et al., “Effectiveness of TNF-α blockade with infliximab in refractory Wegener's granulomatosis,” Rheumatology, vol. 41, no. 11, pp. 1303–1307, 2002. View at: Google Scholar
  43. A. D. Booth, H. J. Jefferson, W. Ayliffe, P. A. Andrews, and D. R. Jayne, “Safety and efficacy of TNFα blockade in relapsing vasculitis,” Annals of the Rheumatic Diseases, vol. 61, no. 6, article 559, 2002. View at: Publisher Site | Google Scholar
  44. M. de Menthon, P. Cohen, C. Pagnoux et al., “Infliximab or rituximab for refractory Wegener's granulomatosis: long-term follow-up. A prospective randomised multicentre study on 17 patients,” Clinical and Experimental Rheumatology, vol. 29, no. 1, pp. S63–S71, 2011. View at: Google Scholar
  45. M. D. Morgan, M. T. Drayson, C. O. S. Savage, and L. Harper, “Addition of infliximab to standard therapy for ANCA-associated vasculitis,” Nephron, vol. 117, no. 2, pp. c89–c97, 2011. View at: Publisher Site | Google Scholar
  46. S. Laurino, A. Chaudhry, A. Booth, G. Conte, and D. Jayne, “Prospective study of TNFα blockade with adalimumab in ANCA-associated systemic vasculitis with renal involvement,” Nephrology Dialysis Transplantation, vol. 25, no. 10, pp. 3307–3314, 2010. View at: Publisher Site | Google Scholar
  47. J. H. Stone, P. A. Merkel, R. Spiera et al., “Rituximab versus cyclophosphamide for ANCA-associated vasculitis,” The New England Journal of Medicine, vol. 363, no. 3, pp. 221–232, 2010. View at: Publisher Site | Google Scholar
  48. C. Roubaud-Baudron, C. Pagnoux, N. Méaux-Ruault et al., “Rituximab maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis,” Journal of Rheumatology, vol. 39, no. 1, pp. 125–130, 2012. View at: Publisher Site | Google Scholar
  49. T. Sakane, M. Takeno, N. Suzuki, and G. Inaba, “Behçet’s disease,” The New England Journal of Medicine, vol. 341, no. 17, pp. 1284–1291, 1999. View at: Publisher Site | Google Scholar
  50. International Study Group for Behçet’s Disease, “Criteria for diagnosis of Behçet’s disease,” The Lancet, vol. 335, no. 8697, pp. 1078–1080, 1990. View at: Google Scholar
  51. H. Yazici, I. Fresko, and S. Yurdakul, “Behçet's syndrome: disease manifestations, management, and advances in treatment,” Nature Clinical Practice Rheumatology, vol. 3, no. 3, pp. 148–155, 2007. View at: Publisher Site | Google Scholar
  52. S. Sahin Ozgun, R. Lawrence, H. Direskeneli, V. Hamuryudan, H. Yazici, and T. Akoglu, “Monocyte activity in Behçet’s disease,” British Journal of Rheumatology, vol. 35, no. 5, pp. 424–429, 1996. View at: Google Scholar
  53. C. Evereklioglu, H. Er, Y. Türköz, and M. Cekmen, “Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet’s disease,” Mediators of Inflammation, vol. 11, no. 2, pp. 87–93, 2002. View at: Google Scholar
  54. S. Muñoz-Fernández, V. Hidalgo, J. Fernández-Melón, A. Schlincker, and E. Martín-Mola, “Effect of infliximab on threatening panuveitis in Behçet's disease,” The Lancet, vol. 358, no. 9293, p. 1644, 2001. View at: Google Scholar
  55. A. Arida, K. Fragiadaki, E. Giavri, and P. P. Sfikakis, “Anti-TNF agents for Behçet's disease: analysis of published data on 369 patients,” Seminars in Arthritis & Rheumatism, vol. 41, no. 1, pp. 61–70, 2011. View at: Publisher Site | Google Scholar
  56. A. A. Okada, H. Goto, S. Ohno, and M. Mochizuki, “Multicenter study of infliximab for refractory uveoretinitis in Behcet disease,” Archives of Ophtalmology, vol. 130, no. 5, pp. 592–598, 2012. View at: Google Scholar
  57. P. P. Sfikakis, P. H. Kaklamanis, A. Elezoglou et al., “Infliximab for recurrent, sight-threatening ocular inflammation in Adamantiades-Behçet disease,” Annals of Internal Medicine, vol. 140, no. 5, pp. 404–406, 2004. View at: Google Scholar
  58. S. Ohno, S. Nakamura, S. Hori et al., “Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behçet's disease with refractory uveoretinitis,” Journal of Rheumatology, vol. 31, no. 7, pp. 1362–1368, 2004. View at: Google Scholar
  59. M. Accorinti, M. P. Pirraglia, M. P. Paroli, R. Priori, F. Conti, and P. Pivetti-Pezzi, “Infliximab treatment for ocular and extraocular manifestations of Behçet's disease,” Japanese Journal of Ophthalmology, vol. 51, no. 3, pp. 191–196, 2007. View at: Publisher Site | Google Scholar
  60. S. Tognon, G. Graziani, and R. Marcolongo, “Anti-TNF-α therapy in seven patients with Behçet's uveitis: advantages and controversial aspects,” Annals of the New York Academy of Sciences, vol. 1110, pp. 474–484, 2007. View at: Publisher Site | Google Scholar
  61. I. Tugal-Tutkun, A. Mudun, M. Urgancioglu et al., “Efficacy of infliximab in the treatment of uveitis that is resistant to treatment with the combination of azathioprine, cyclosporine, and corticosteroids in Behçet's disease: an open-label trial,” Arthritis & Rheumatism, vol. 52, no. 8, pp. 2478–2484, 2005. View at: Publisher Site | Google Scholar
  62. N. Markomichelakis, E. Delicha, S. Masselos, and P. P. Sfikakis, “Intravitreal infliximab for sight-thretening relapsing uveitis in Behcet disease : a pilot study in 15 patients,” The American Journal of Ophtalmology, vol. 154, no. 3, pp. 534–554, 2012. View at: Google Scholar
  63. D. Perra, M. A. Alba, J. L. Callejas et al., “Adalimumab for the treatment of Behcet’s disease : experience in 19 patients,” Rheumatology, vol. 51, no. 10, pp. 1825–1831, 2012. View at: Google Scholar
  64. N. R. Benitah, L. Sobrin, and G. N. Papaliodis, “The use of biologic agents in the treatment of ocular manifestations of Behçet’s disease,” Seminars in Ophthalmology, vol. 26, no. 4-5, pp. 295–303, 2011. View at: Publisher Site | Google Scholar
  65. M. Mesquida, M. Victoria Hernàndez, V. Llorenç et al., “Behçet disease-associated uveitis successfully treated with golimumab,” Ocular Immunology and Inflammation, vol. 21, no. 2, pp. 160–162, 2013. View at: Google Scholar
  66. M. Melikoglu, I. Fresko, C. Mat et al., “Short-term trial of etanercept in Behçet's disease: a double blind, placebo controlled study,” Journal of Rheumatology, vol. 32, no. 1, pp. 98–105, 2005. View at: Google Scholar
  67. S. Iwata, K. Saito, K. Yamaoka et al., “Effects of anti-TNF-α antibody infliximab in refractory entero-Behçet's disease,” Rheumatology, vol. 48, no. 8, pp. 1012–1013, 2009. View at: Publisher Site | Google Scholar
  68. C. de Cassan, B. de Vroey, C. Dussault, E. Hachulla, S. Buche, and J.-F. Colombel, “Successful treatment with adalimumab in a familial case of gastrointestinal Behçet’s disease,” Journal of Crohn's & Colitis, vol. 5, no. 4, pp. 364–368, 2011. View at: Publisher Site | Google Scholar
  69. H. Kikuchi, K. Aramaki, and S. Hirohata, “Effect of infliximab in progressive Neuro-Behçet's syndrome,” Journal of the Neurological Sciences, vol. 272, no. 1-2, pp. 99–105, 2008. View at: Publisher Site | Google Scholar
  70. A. Giardina, A. Ferrante, F. Ciccia, M. Vadalà, E. Giardina, and G. Triolo, “One year study of efficacy and safety of infliximab in the treatment of patients with ocular and neurological Behçet's disease refractory to standard immunosuppressive drugs,” Rheumatology International, vol. 31, no. 1, pp. 33–37, 2011. View at: Publisher Site | Google Scholar
  71. J. Belzunegui, L. López, I. Paniagua, J. J. Intxausti, and O. Maíz, “Efficacy of infliximab and adalimumab in the treatment of a patient with severe neuro-Behçet's disease,” Clinical and Experimental Rheumatology, vol. 26, no. 4, supplement 50, pp. S133–S134, 2008. View at: Google Scholar
  72. J. E. Alty, T. M. Monaghan, and J. M. Bamford, “A patient with neuro-Behçet's disease is successfully treated with etanercept: further evidence for the value of TNFα blockade,” Clinical Neurology and Neurosurgery, vol. 109, no. 3, pp. 279–281, 2007. View at: Publisher Site | Google Scholar
  73. P. Leccese, L. Latanza, S. D'Angelo, A. Padula, and I. Olivieri, “Efficacy of switching to adalimumab in a patient with refractory uveitis of Behçet's disease to infliximab,” Clinical and Experimental Rheumatology, vol. 29, no. 4, supplement 67, p. S93, 2011. View at: Google Scholar
  74. J. A. Singh, G. A. Wells, R. Christensen et al., “Adverse effects of biologics: a network meta-analysis and Cochrane overview,” Cochrane Database of Systematic Reviews, vol. 16, no. 2, Article ID CD008794, 2011. View at: Google Scholar
  75. C. Salliot, L. Gossec, A. Ruyssen-Witrand et al., “Infections during tumour necrosis factor-α blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients,” Rheumatology, vol. 46, no. 2, pp. 327–334, 2007. View at: Publisher Site | Google Scholar
  76. A. A. den Broeder, L. A. B. Joosten, T. Saxne et al., “Long term anti-tumour necrosis factor α monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation,” Annals of the Rheumatic Diseases, vol. 61, no. 4, pp. 311–318, 2002. View at: Publisher Site | Google Scholar
  77. E. C. Keystone, M. H. Schiff, J. M. Kremer et al., “Once-weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: results of a multicenter, randomized, double-blind, placebo-controlled trial,” Arthritis & Rheumatism, vol. 50, no. 2, pp. 353–363, 2004. View at: Publisher Site | Google Scholar
  78. E. C. Keystone, A. F. Kavanaugh, J. T. Sharp et al., “Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial,” Arthritis & Rheumatism, vol. 50, no. 5, pp. 1400–1411, 2004. View at: Publisher Site | Google Scholar
  79. E. W. St.Clair, D. M. F. M. van der Heijde, J. S. Smolen et al., “Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial,” Arthritis & Rheumatism, vol. 50, no. 11, pp. 3432–3443, 2004. View at: Publisher Site | Google Scholar
  80. J. Askling and W. Dixon, “The safety of anti-tumour necrosis factor therapy in rheumatoid arthritis,” Current Opinion in Rheumatology, vol. 20, no. 2, pp. 138–144, 2008. View at: Publisher Site | Google Scholar
  81. J. Keane, S. Gershon, R. P. Wise et al., “Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent,” The New England Journal of Medicine, vol. 345, no. 15, pp. 1098–1104, 2001. View at: Publisher Site | Google Scholar
  82. J. Askling, R. F. van Vollenhoven, F. Granath et al., “Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor α therapies: does the risk change with the time since start of treatment?” Arthritis & Rheumatism, vol. 60, no. 11, pp. 3180–3189, 2009. View at: Publisher Site | Google Scholar
  83. F. Wolfe and K. Michaud, “The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation,” Arthritis & Rheumatism, vol. 56, no. 5, pp. 1433–1439, 2007. View at: Publisher Site | Google Scholar
  84. F. Wolfe and K. Michaud, “Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study,” Arthritis & Rheumatism, vol. 56, no. 9, pp. 2886–2895, 2007. View at: Publisher Site | Google Scholar
  85. J. Kelsall, P. Rogers, G. Galindo, and M. A. de Vera, “Safety of infliximab treatment with rheumatoid arthritis in a real-world clinical setting : description and évaluation of infusion reactions,” Journal of Rheumatology, vol. 39, no. 8, pp. 1539–1545, 2012. View at: Google Scholar
  86. L. de Rycke, D. Baeten, E. Kruithof, F. van den Bosch, E. M. Veys, and F. de Keyser, “The effect of TNFalpha blockade on the antinuclear antibody profile in patients with chronic arthritis: biological and clinical implications,” Lupus, vol. 14, no. 12, pp. 931–937, 2005. View at: Publisher Site | Google Scholar
  87. N. Mohan, E. T. Edwards, T. R. Cupps et al., “Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides,” Arthritis & Rheumatism, vol. 44, no. 12, pp. 2862–2869, 2001. View at: Google Scholar

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