Efficacy of Biological-Targeted Treatments in Takayasu Arteritis
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Abstract
Background—
The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-α antagonists and tocilizumab) in patients with Takayasu arteritis.
Methods and Results—
This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20–55 years] treated by tumor necrosis factor-α antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1–5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10–46 mg/L] versus 58 mg/L [26–76 mg/L]; P=0.006) and a trend toward fewer immunosuppressants drugs used before biologics (P=0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [P<0.05] and 15 versus 7.5 mg [P<0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%–99%) over the biological treatment period compared with 58.7% (43.3%–79.7%; P=0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-α antagonists and tocilizumab. After a median follow-up of 24 months (2–95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases.
Conclusion—
This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile.
Introduction
Takayasu arteritis (TA) is a chronic inflammatory vasculitis of unknown origin affecting large vessels, predominantly the aorta and its main branches.1 Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation. Symptoms result from systemic inflammation or end-organ ischemia. More acute inflammation can alter and weaken the arterial media, leading to aneurysm formation. Once thought to be a disorder that affected mostly young Asian women, TA has now been identified in both sexes and many ethnic and racial groups worldwide. The first-line therapy is based on steroids. Approximately one half of all patients with TA have steroid-resistant or relapsing diseases for which the addition of other immunosuppressive agents to steroid therapy may be required to achieve remission. Azathioprine, methotrexate, or mycophenolate mofetil is used when steroids fail to maintain remission or in patients with steroid dependence, which can lead to adverse effects of glucocorticoids.2–4
Editorial see p 1685
Clinical Perspective on p 1700
The pathogenesis of TA remains unclear but includes vessel injury caused by products and various cytokines from activated T cells, natural killer cells, γ/δ cells, and macrophages.5 Tumor necrosis factor-α (TNF-α) production occurs primarily in macrophages, T cells, and natural killer cells and is important in the formation of granuloma. Furthermore, serum interleukin (IL)-6 level has been correlated with disease activity in TA. In animal models, mice deficient in interferon regulatory factor 4–binding protein, a protein that inhibits IL-17A production by controlling the activity of interferon regulatory factor 4 transcription factor, rapidly developed large-vessel vasculitis as a result of an inappropriate synthesis of IL-17A.6
Preliminary studies have reported the efficacy of biological-targeting treatments such as TNF-α antagonists (infliximab, adalimumab, etanercept) and anti–IL-6 receptor (tocilizumab) in TA refractory to other immunosuppressive therapies.7–25 Here, we report the long-term outcome of 49 TA patients treated with TNF-α antagonists and tocilizumab in this French nationwide study, and we compare their safety, their efficacy, and the factors predictive of treatment response.
Methods
We conducted a retrospective, multicenter study in referral centers from the French Takayasu network between 2001 and 2013. This study was approved by the local ethics committee. All patients fulfilled TA American College of Rheumatology or Ishikawa criteria modified by Sharma.26 The patients’ clinical, laboratory, and imaging data and their treatments were analyzed at baseline; at the initiation of each new treatment regimen; at 3, 6, 12, and 18 months and 3 years after each treatment line; and at the last available visit. Glucocorticosteroid doses were analyzed at the initiation of each new treatment regimen and during follow-up. Routine laboratory indicators of disease activity, including erythrocyte sedimentation rate and C-reactive protein (CRP) levels, were collected. Disease-specific complications related to TA, defined as the occurrence of any ischemic vascular event, the need for vascular intervention, or death, were analyzed during the follow-up. The different lines of immunosuppressive agents (disease-modifying antirheumatic drugs [DMARDs]) and of biological-targeting treatments were analyzed separately for each patient. Biological-targeting treatment was prescribed in 88% of TA patients because they were inadequately controlled with or were intolerant to DMARDs (n=43) and in 12% of cases (n=6) as first-line treatment (Figure 1). Fifteen patients in the present case series have been reported previously,15 but an extension of follow-up was provided for these patients.
Figure 1. Flowchart of long-term use of biological-targeted treatment in 49 patients with Takayasu arteritis. DMARD indicates disease-modifying antirheumatic drug; TNF-α, tumor necrosis factor-α; and TOCI, tocilizumab.
Disease Activity and Treatment Response Definitions
Disease activity was defined according to the National Institutes of Health (NIH) criteria: (1) new ischemic vascular sign (ie, claudication, bruit, or asymmetry in pulses or blood pressure, carotidynia, pulselessness); (2) new arterial lesion or worsening of pre-existing lesions on imaging, visualized by angio-computed tomography or magnetic resonance imaging or angiography; (3) systemic clinical feature (ie, weight loss, fever, or myalgia); and (4) biological activity, that is, increased erythrocyte sedimentation rate or CRP level.27 Disease was considered active if NIH score was ≥2 and inactive otherwise. Steroid dependence was defined as prednisone ≥20 mg/d during at least 1 month before each new therapy.
Treatment response to any regimen (DMARDs, biological-targeting treatment) was defined as complete response in the case of NIH scale <2 and prednisone <10 mg/d, as partial response when the steroid dose decreased by at least 50% compared with baseline, and nonresponse in other situations. Relapse was defined as the disease becoming active after a remission period, requiring change of the treatment regimen.
Assessment of Tolerance of Biological-Targeting Treatments
Adverse events were recorded in a specific questionnaire. Severe infection was defined as any infection requiring intravenous antibiotic use or hospitalization or an infection-related death.
Statistical Analysis
Data are presented as medians with extreme ranges for continuous variables and frequencies with percentages for qualitative variables. The Fisher exact test was used to compare qualitative variables, and the Wilcoxon rank-sum test was used to compare continuous variables as appropriate. Relapse-free survival in patients receiving treatments was estimated with the Kaplan-Meier estimator. Because each patient could experience multiple relapses, we considered an Andersen-Gill approach in which treatment is a time-dependent covariate.28 Thus, the time origin for each treatment was the time at which the subject started on that regimen. Treatment switch resulting from a lack of efficacy or an intolerance was considered a competing event of relapse without intolerance and then censored in the analysis. In case of no event, patients were censored at the time of their last follow-up. Differences between survivals curves were tested with Wald tests. Hazard ratios and their 95% confidence intervals of the cause-specific hazard of relapse were obtained from the Cox proportional hazard model. Moreover, variances of the models were estimated with the use of a generalized estimating equation approach to take into account potential correlations between observations within each patient. The impact of biological-targeted treatments was also assessed after adjustment for the CRP level. Cumulative incidence of complications was estimated with Gray estimator, with relapse without complication considered a competing event of complication.29,30 Differences between cumulative incidences were tested with Gray test. All tests were 2 sided, and a value P<0.05 was considered statistically significant. Statistical analyses were carried out with R (version 3.1.0).
Results
Patients’ Baseline Characteristics
Forty-nine patients with TA were included. Their median age was 42 years (20–55 years), and 39 (80%) were female. Geographic origin included 25 whites (51%), 12 (24.5%) North Africans, and 12 (24.5%) from other origins. According to the Numano classification, 6 patients (13%) had type I, 14 (29%) had type II, 2 (4%) had type III, 2 (4%) had type IV, and 24 (50%) had type V. The Ishikawa score was 3 in 13 patients (59%). At TA diagnosis, arterial hypertension was present in 13 of 46 patients (28%), diabetes mellitus in 3 of 46 (6%), hyperlipidemia in 8 of 46 (17%), and tobacco use in 16 of 45 (36%). The median body mass index was 21.5 kg/m2 (18.7–24.2 kg/m2). Patient characteristics before biological-targeting treatments and during the follow-up are summarized in Table 1. At the initiation of the biological-targeting treatments, vascular signs were present in 39 patients (67%) and constitutional signs were seen in 25 (46%). The main vascular signs included upper-limb claudication (30%), lower-limb claudication (19%), vascular bruit (70%), decrease or absent radial pulse (48%), blood pressure difference >10 mm Hg (45%), carotidynia (33%), and aortic regurgitation (16%).
| Initiation of Biologics (n=70 lines of treatment) | At 3 mo (n=43 lines of treatment)* | At 6 mo (n=42 lines of treatment) | At 12 mo (n=40 lines of treatment) | At 18 mo (n=33 lines of treatment) | At 3 y (n=19 lines of treatment) | |
|---|---|---|---|---|---|---|
| Vascular signs, n (%) | 38 (67)† | 8 (19) | 8 (19) | 8 (22) | 5 (19) | 4 (21) |
| Constitutional signs, n (%) | 26 (46%)† | 4 (9) | 6 (14) | 1 (3%) | 4 (14) | 0 () |
| NIH activity score | 2 (1–4)‡ | 0 (0–2) | 0.5 (0–3) | 0 (0–3) | 0 (0–3) | 0 (0–3) |
| C-reactive protein, mg/L | 30 (1–200)‡ | 6 (0–100) | 5 (0–40) | 6 (0–100) | 5 (0–76) | 5 (0–50) |
| Prednisone, n (%) | 63 (89) | 40 (93) | 36 (86) | 36 (86) | 25 (74) | 13 (68) |
| Prednisone amount, mg/d | 15 (4–75)‡ | 12.5 (4–50) | 10 (1–30) | 7.5 (1–30) | 5 (0–20) | 5 (0–12) |
| Associated DMARDs, n (%) | 56 (76) | 37 (86) | 32 (76) | 35 (83) | 24 (75) | 13 (68) |
| Methotrexate | 40 (73) | 27 (73) | 21 (66) | 23 (66) | 14 (58) | 8 (62) |
| Azathioprine | 13 (24) | 8 (22) | 9 (28) | 10 (29) | 10 (42) | 5 (38) |
| Others | 3 (3) | 2 (5) | 2 (6) | 2 (5) | .. | … |
| Complete response to biological-targeting treatment, n (%) | … | 16 (39) | 25 (64) | 30 (75) | 22 (67) | 13 (76) |
| Partial response to biological-targeting treatment, n (%) | … | 19 (44) | 5 (12) | 3 (8) | 7 (21) | 3 (18) |
| No response to biological-targeting treatment, n (%) | … | 7 (17) | 10 (26) | 7 (18) | 4 (12) | 1 (8) |
Treatment
Among the 49 TA patients, 70 lines of biological-targeting treatments were used during the follow-up after a median of 3 DMARDs (range, 1–5). Among the biological-targeting treatments, patients were treated by TNF-α antagonists (n=56 lines of therapy, 80%; ie, infliximab [n=44], etanercept [n=6], and adalimumab [n=6]) or tocilizumab (n=14 lines of therapy, 20%). The median treatment duration of biological-targeting treatments was 16 months (2–85 months). Infliximab was used at a median dose of 5 mg/kg (3–7 mg/kg) at weeks 0, 2, and 6 and then every 6 weeks (4–8 weeks); etanercept, 25 mg twice a week; adalimumab, 40 mg every 2 weeks; and tocilizumab, 8 mg/kg monthly.
Efficacy of Biologics
A complete or partial response to biological-targeting treatments at 3, 6, and 12 months was seen in 16 (39%) and 18 (44%), in 25 (64%) and 4 (11%), and in 30 (75%) and 3 (8%) patients, respectively (Table 1). NIH score (2 [1–4] at baseline versus 0 [0–3] at 12 months; P<0.05), CRP level (30 mg/L [1–200 mg/L] at baseline versus 6 mg/L [0–100 mg/L] at 12 months; P<0.05), and daily prednisone dose (15 mg [4–75 mg] at baseline versus 7.5 mg [1–30 mg] at 12 months; P<0.05) significantly decreased after 12 months of biological-targeting treatments (Table 1). In responders (ie, complete or partial response) relative to nonresponders, CRP level at initiation of biological-targeting treatments was lower (22 mg/L [10–46 mg/L] versus 58 mg/L [26–76 mg/L]; P=0.006), and there was a trend toward lower prior DMARD use (P=0.054) before biological-targeting treatments.
At least 1 switch to another biological-targeting treatment was necessary during the follow-up in 40% and 29% of patients receiving TNF-α antagonists and tocilizumab, respectively (Figure 1).
Comparison of Biologics to Previous DMARDs
DMARDs were used in 43 of 49 patients before the biologics (methotrexate [n=28], azathioprine [n=7], and others immunosuppressants [n=8]). Patient characteristics at biological-targeting treatment initiation compared with those at DMARD initiation showed no difference in NIH score, CRP level, or proportion of vascular and constitutional signs but a higher number of previous treatment regimens (3 [1–5] versus 2 [1–4]; P<0.05) and a lower prednisone daily dose (15 mg [4–70 mg] versus 30 mg [4–80 mg]; P<0.05). Up to 76% of cases had DMARDs (methotrexate [n=40], azathioprine [n=13], and others [n=3]) associated with the newly introduced biological-targeting treatment. The 3-year relapse-free survival after biological-targeting treatment initiation compared with the period before (ie, DMARDs period) was 90.9% (83.5%–99.0%) versus 58.7% (43.3–79.7; P=0.009), respectively (Figure 2). After adjustment for CRP level, relapse-free survival remained better after biological-targeting treatment initiation compared with the period before (ie, DMARDs period; hazard ratio, 0.26; 95% confidence interval, 0.09–0.73; P=0.01). Similarly, the 3-year cumulative incidence of vascular complication was 5.1% versus 16.6% (P=0.08) after biological-targeting treatment initiation compared with the period before (DMARDs period), respectively (Figure 3).
Figure 2. Relapse-free survival in 49 patients with Takayasu arteritis according to disease-modifying antirheumatic drugs (DMARDs; n=73 lines of therapy) and to biological-targeted treatment (n=70 lines of therapy).
Figure 3. Cumulative incidence of vascular complications in 49 patients with Takayasu arteritis according to disease-modifying antirheumatic drugs (DMARDs; n=73 lines of therapy) and biological-targeted treatment (n=70 lines of therapy).
Comparison of TNF-α Antagonists and Tocilizumab
The comparison of patients treated with TNF-α antagonists (n=56 lines of therapy) with those receiving tocilizumab (n=14 lines of therapy) showed that the proportion of complete or partial responses did not differ at 3, 6, and 12 months (Table 2). CRP levels and the prednisone daily dose tended to be lower at 12 months in TA patients treated with tocilizumab (Table 2). The proportion of vascular complications was equivalent in those receiving TNF-α antagonists and patients receiving tocilizumab (7 [13%] versus 1 [7%], respectively; P>0.05). The number of vascular interventions was equivalent in those receiving TNF-α antagonists and in patients receiving tocilizumab (6 [11%] versus 1 [7%], respectively; P>0.05). The 3-year relapse-free survival in patients on TNF-α antagonists and those on tocilizumab was 91% and 85.7%, respectively (P=0.81; Figure 4).
| Initiation of Biologics | At 3 mo* | At 6 mo | At 12 mo | |||||
|---|---|---|---|---|---|---|---|---|
| TNF-α Antagonists (n=56 lines of therapy) | Tocilizumab (n=14 lines of therapy) | TNF-α Antagonists (n=33) | Tocilizumab (n=10) | TNF-α Antagonists (n=32) | Tocilizumab (n=10) | TNF-α Antagonists (n=33) | Tocilizumab (n=7) | |
| Vascular signs, n (%) | 28 (65) | 8 (73) | 5 (21) | 2 (20) | 6 (24) | 2 (20) | 6 (23) | 1 (17) |
| Constitutional signs, n (%) | 17 (40) | 7 (64) | 3 (13) | 1 (10) | 6 (24) | 0 | 1 (4) | 0 |
| NIH activity score | 2 (1–4) | 3 (2–4) | 0 (0–2) | 0 (0–2) | 1 (0–3) | 0 (0–2)† | 0 (0–3) | 0 (0)† |
| NIH score ≥2, n (%) | 47 (92) | 14 (100) | 6 (19) | 1 (10) | 9 (31) | 1 (10) | 6 (21) | 0 |
| C-reactive protein, mg/L | 30 (2–170) | 24 (6–200) | 6 (0–100) | 2 (0–21) | 5 (0–140) | 2 (0–87)† | 9 (0–100) | 0 (0–8)‡ |
| Prednisone, n (%) | 28 (68) | 11 (79) | 30 (94) | 7 (70)† | 28 (88) | 6 (60)† | 26 (90) | 4 (57)† |
| Prednisone, mg/d | 15 (4–50) | 12.5 (4–75) | 14 (4–40) | 10 (7–24) | 9 (1–20) | 10 (4–30) | 7.5 (5–20) | 4.5 (1–14) |
| DMARDs, n (%) | 45 (80) | 8 (57)† | 29 (88) | 6 (60) | 25 (78) | 5 (50) | 26 (90) | 4 (57)† |
| Complete response, n (%) | … | .. | 11 (35) | 5 (50) | 17 (61) | 7 (70) | 23 (74) | 7 (100) |
| Partial response | … | … | 14 (45) | 4 (40) | 2 (7) | 2 (20) | 1 (3) | 0 |
| Nonresponse, n (%) | … | … | 6 (19) | 1 (10) | 9 (32) | 1 (10) | 7 (23) | 0 |
Figure 4. Relapse-free survival in 49 patients with Takayasu arteritis according to treatment with tumor necrosis factor-α (TNFα) antagonists (n=56 lines) and tocilizumab (n=14 lines).
Safety
During the median follow-up of 24 months (2–95 months), 16 (21%) adverse effects occurred: infection (n=9: 1 Epstein-Barr virus reactivation [with infliximab], 1 zona [with infliximab], 1 tuberculosis reactivation [with infliximab], and 6 severe bacterial infections [4 with infliximab, 1 with etanercept, and 1 with tocilizumab]), infusion-related reactions (n=4; all with infliximab), neoplasms (n=2: 1 lung cancer [with infliximab] and 1 breast cancer [with tocilizumab]), and 1 severe asymptomatic neutropenia (<500/mm3 [with tocilizumab]). Among the 6 severe bacterial infections, there were 2 erysipelas (with infliximab), 2 complicated pharyngitis, 1 dental abscess (with tocilizumab), and 1 tonsillar cellulitis (with etanercept). Six patients (10%) required treatment discontinuation, including 3 patients with infusion-related reactions, 2 with neoplasms, and 1 with severe infection (tonsillar cellulitis). The breast neoplasm occurred in a patient with family history of neoplasm (breast neoplasm in sister), and the lung cancer occurred in a patient with previous alcohol and tobacco use. No significant difference was observed between TNF-α antagonists (side effects in 13 of 56 patients, 23.2%) and tocilizumab (side effects in 3 of 14 patients, 21.4%; P>0.05) relative to safety.
Discussion
The conclusions of this study are that biological-targeted treatments (ie, TNF-α antagonists or tocilizumab) can lead DMARD-refractory TA to remission with 93% improvement (ie, complete and partial responders) at 12 months, and 75% of patients being complete responders, with a relatively good safety profile. TNF-α antagonists and tocilizumab seem to have equivalent efficacy and tolerance. This is the largest study assessing the long-term outcome of biological-targeted treatments in TA. In steroid-resistant or -dependent TA patients, the addition of DMARDs (methotrexate, azathioprine, mycophenolate mofetil) to the ongoing steroid therapy often allows better disease control and the tapering of steroids.2,31 However, clinical relapses and progression of vascular involvement remain frequent.1 Patients with uncontrolled disease with immunosuppressive agents can benefit from biological-targeted treatments. Strikingly, the efficacy of biologics was evident as early 3 months, with 83% improvement noted in TA patients. Relapse-free survival was 4 times higher after relative to before biological-targeted treatment initiation with the prior therapy including DMARDs. Moreover, biological-targeted treatments had a significant steroid-sparing effect with a prednisone daily dose reduced by 50% at 12 months. Only 58% of the TA patients were taking steroids after 3 years of follow-up after compared with 82% before biological-targeted treatment initiation. This is especially important because patients receiving a high cumulative dose of steroids are exposed to high risks of side effects. Factors associated with a better response to biological-targeted treatments included a significantly lower CRP level and a lower number of DMARDs used before biological-targeted treatment initiation. This may suggest that biological-targeted treatments might be used earlier in the treatment of refractory TA patients.
We found no difference in efficacy between TNF-α antagonists and tocilizumab. The proportions of complete and partial response at 3, 6, and 12 months were equivalent for TNF-α antagonists and tocilizumab. The proportions of vascular complications and relapse-free survival were similar for TNF-α antagonists and tocilizumab. No significant difference in terms of safety was observed between these biological-targeted treatments, with up to 20% of side effects.
In 5 major observational uncontrolled cohorts, TNF-α antagonists were studied in a total of 90 refractory TA patients.10,13,15,16,22 Complete or partial response was observed in 85% to 90% of patients, with a relapse rate of 33% to 60%. New vascular lesions were observed in 16% to 33% of patients.16,22 Disease relapses were observed in 13 of the 14 total patients with suspended biological-targeted treatment after longstanding remission.13,16,22 A satisfactory response was observed after TNF-α antagonists were resumed. Preliminary experience proposed that tocilizumab, a humanized anti–IL-6 receptor antibody, could be another option for refractory TA.18 A recent literature review observed a steroid-sparing activity of tocilizumab with a good clinical and laboratory response.7 Tocilizumab was effective in several patients refractory to TNF-α antagonists, but relapses were frequent after its discontinuation, necessitating long-term maintenance therapy. Goel et al12 reported that 6 of 10 patients treated with tocilizumab for 6 months remained radiologically stable, as evaluated by angiography or Doppler ultrasonography. Nakaoka et al17 reported 4 patients (2 of whom were previously treated by steroids) treated by tocilizumab for >2 years who were followed up with both magnetic resonance imaging and computed tomography. They observed imaging stabilization in 2 patients and improvement in the remaining 2 patients. Interestingly, serum IL-6 levels initially increased and then were progressively reduced in parallel with an improvement in arterial thickened lesions, suggesting progressive reduction of IL-6 production. Tombetti et al24 reported their experience with 7 refractory patients treated with tocilizumab for a median of 14 months. Three of their 7 patients had complete response and imaging evidence of stabilization of or improvement in all arterial lesions after treatment with tocilizumab.
Safety is always an issue with biological agents. In our study, side effects occurred in 21% of cases, and 7% required treatment interruption. A similar rate was reported in a literature review of 84 patients treated with TNF-α antagonists, mainly infections and infusion-related reactions.10 Along this line, a literature review of TA treated with tocilizumab7 reported a low rate of severe adverse effects, mainly infections, a few cases of hyperlipidemia, and neutropenia. Without overlooking the shorter experience with tocilizumab, it seems that TNF-α antagonists and tocilizumab have the same safety. Several meta-analyses showed no risk of cancer with biologics except skin localization.32,33 Several other risk factors could be argued in our 2 cases of neoplasms under biologics.
Our study had several limitations. The retrospective design of this series resulted in a lack of uniformity in biological-targeted treatments. Treatment decisions were left at the physician’s discretion. Evaluation of the efficacy of etanercept and adalimumab was difficult because of the low number of patients treated with these drugs. This low number of patients had also on impact on our capability to perform a more complicated statistical model. Nevertheless, the results observed were similar when the potential correlation between observations owing to the multiple treatments per patient was taken into account. Adjustment for CRP level at treatment initiation gave also similar conclusions.
Conclusions
This French nationwide study is the largest study assessing the long-term efficacy of TNF-α antagonists and tocilizumab in patients with TA refractory to DMARDs. We observed good efficacy of these drugs with reasonable safety profiles. TNF-α antagonists and tocilizumab seem to have equivalent efficacy and tolerance. Prospective, randomized studies are warranted to go beyond these conclusions for better care of TA patients refractory to DMARDs.
Acknowledgments
We thank the Club Rhumatismes et Inflammation and the French National Society of Internal Medicine for help in the organization of this study.
Disclosures
None.
Footnotes
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CLINICAL PERSPECTIVE
Takayasu arteritis (TA) is a chronic inflammatory vasculitis of unknown origin affecting large vessels, predominantly the aorta and its main branches. The first-line therapy is based on steroids, but one-half of TA patients have steroid-resistant or relapsing diseases for which the addition of other immunosuppressive agents to steroid therapy may be required to achieve remission. Preliminary studies have reported the efficacy of biological-targeting treatments such as TNF-α antagonists and anti-IL-6 receptor (tocilizumab) in TA refractory to other immunosuppressive therapies, but long-term outcome and comparison to disease-modifying antirheumatic drugs and between biologics are lacking. In this study we demonstrate that biological-targeted treatments (ie, TNF-α antagonists and tocilizumab) can lead steroids or disease-modifying antirheumatic drugs-refractory TA to remission with 93% of improvement (ie, complete and partial responders) at 12 months. The 3-year relapse-free survival after biological-targeting treatment initiation compared to the period ‘before’ (ie, disease-modifying antirheumatic drugs period, mainly methotrexate and azathioprine) was of 90.9% (83.5–99.0) versus 58.7% (43.3–79.7), (p=0.009), respectively. The 3-year cumulative incidence of vascular complication was of 5.1% versus 16.6%, (p=0.08), after biological-targeting treatment initiation compared to the period ‘before’ (ie, disease-modifying antirheumatic drugs period), respectively. The proportion of vascular complications was equivalent under TNF-α antagonists and tocilizumab (7 [13%] versus 1 [7%], p>0.05), respectively. The 3-year relapse free survival under TNF-α antagonists and tocilizumab were 91% and 85.7%, (p=0.81), respectively. Thus, TNF-α antagonists and tocilizumab seem to have similar efficacy in TA. Biological-targeted treatments (ie, TNF-α antagonists or tocilizumab) in TA have relatively good safety profile.
