Tab Application Banner
  • Users Online: 1238
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 12  |  Issue : 3  |  Page : 139-145

Clinical experience with two etanercept biosimilars in Indian patients with spondyloarthritis


Department of Rheumatology, Fortis Flt. Lt. Rajan Dhall Hospital, New Delhi, India

Date of Web Publication27-Jul-2017

Correspondence Address:
Ashok Kumar
Department of Rheumatology, Fortis Flt. Lt. Rajan Dhall Hospital, Vasant Kunj, New Delhi - 110 070
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injr.injr_40_17

Rights and Permissions
  Abstract 

Background: Antitumor necrosis factor (TNF) drugs are highly efficacious in spondyloarthritis (SpA). We present retrospective analysis of our experience with 2 etanercept biosimilars (Etacept and Intacept).
Methods: Clinical record of patients with axial and/or peripheral SpA (Assessment of SpA International Society [ASAS] criteria) registered during April 2013–September 2016 was retrieved. Those with active disease (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] >4), despite 1-month trial of two non-steroidal anti-inflammatory drugs (NSAIDs) (axial) and/or 3-month trial of disease modifying anti-rheumatic drugs (peripheral), received anti-TNF therapy. Etanercept biosimilar (50 mg) was administered weekly for the first 12 weeks. Patients achieving “major improvement” after 12 weeks (Ankylosing Spondylitis Disease Activity Score [ASDAS] reduction by >2 points) received the dose every 2 weeks subsequently. BASDAI, Bath Ankylosing Spondylitis Functional Index, and ASDAS and NSAID index were noted at baseline, 12, and 24 weeks. For Etacept, week 52 and 104 data were also available. Primary endpoint was BASDAI <4 at 12 weeks.
Results: Males constituted the majority (76%) and mean ASDAS was 4.7. In patients receiving Etacept, BASDAI <4 and major improvement were achieved by 12 weeks in 77% (42/54) and 61% (33/54) patients, respectively. Forty-three patients had completed 52 weeks and 27 patients had completed 104 weeks of treatment. Among 27 patients completing 104 weeks, secondary end points: ASAS 20, 40, and ASAS-partial remission status were achieved by 89%, 67%, and 41%, respectively. Intacept results were available up to 24 weeks and were comparable to those of Etacept. Injection site reactions followed by upper respiratory tract infections were the most common adverse reactions. One patient developed tuberculous pleural effusion.
Conclusion: Etanercept biosimilar therapy was found efficacious and safe.

Keywords: Antitumor necrosis factor, biological, biosimilar, etanercept, spondyloarthritis


How to cite this article:
Kumar A, Goel A, Lapsiwala M, Goyal M, Dembla G. Clinical experience with two etanercept biosimilars in Indian patients with spondyloarthritis. Indian J Rheumatol 2017;12:139-45

How to cite this URL:
Kumar A, Goel A, Lapsiwala M, Goyal M, Dembla G. Clinical experience with two etanercept biosimilars in Indian patients with spondyloarthritis. Indian J Rheumatol [serial online] 2017 [cited 2019 May 21];12:139-45. Available from: http://www.indianjrheumatol.com/text.asp?2017/12/3/139/211696


  Introduction Top


Spondyloarthritis (SpA) is an important category of chronic inflammatory joint disease.[1] The socioeconomic burden of SpA can be considerable, due to work disabilities, use of healthcare resources, and sometimes to the patient's depressed mood or low social functioning.[2],[3],[4],[5],[6],[7] The first-line therapy for the axial SpA consists of nonsteroidal anti-inflammatory drugs (NSAIDs) and regular exercise, but they are not effective in many cases. Disease modifying anti-rheumatic drugs (DMARDs) such as sulfasalazine, methotrexate, or leflunomide are recommended for treating peripheral arthritis or extra-articular features. However, in patients refractory to above measures, antitumor necrosis factor (TNF) drug is a reliable option. The Assessment of SpA International Society (ASAS) recommends use of anti-TNF in patients diagnosed with AS or SpA if they have active disease and have not improved with conventional treatment (NSAIDs and DMARDs).[8] All four TNF-alpha blockers currently available in India for the treatment of AS (infliximab, adalimumab, etanercept, and golimumab) demonstrated similar high efficacy in patients who did not respond to previous NSAIDs therapy.[9],[10],[11],[12] As patents for innovator anti-TNF drugs expire, pharmaceutical manufacturers have developed copies of innovator molecules at considerably lower production cost. These have also been called “biosimilars” by NICE. Biosimilar is a biological medicine which has been shown not to have any clinically meaningful differences from the originator biological drug in terms of quality, safety, and efficacy.“[13] We report our clinical experience with two etanercept biosimilars in patients with SpA. These local biosimilars are approved by the Drug Controller General of India. We used “Etacept” (introduced in the Indian market with effect from April 2013) and “Intacept” (introduced with effect from April 2015). We also tried to examine if the efficacy of etanercept biosimilars was sustained after reducing the dosing frequency.


  Methods Top


This was a retrospective chart review in which we retrieved the clinic records of patients who fulfilled the following inclusion criteria;

  1. Patients with axial and/or peripheral SpA (according to ASAS criteria) attending our rheumatology clinic during April 2013–September 2016 and
  2. Those with active disease (>4 Bath Ankylosing Spondylitis Disease Activity Index [BASDAI])[14] despite a 1-month trial of at least two NSAIDs (for axial symptoms only) with or without 3-month trial of DMARDs (for peripheral joint symptoms).


Following patients were excluded;

  1. Patients who did not complete at least 12 weeks of etanercept biosimilar therapy or
  2. Patients with active tuberculosis, current or past history of hepatitis B, hepatitis C or human immunodeficiency virus, demyelinating disease, alcohol abuse, psychiatric illness, symptoms of severe and progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease, congestive heart failure, history of any form of cancer within the past 10 years, history of serious infection requiring hospitalization in the past 6 months, and history of any surgery in the past 12 weeks. Women with pregnancy or who were breastfeeding were also excluded from the study.


Screening for latent tuberculosis (TB) included chest X-ray, interferon gamma release assay (“Quantiferon-TB-Gold“), and Mantoux test (1 TU). In addition, hepatitis B surface antigen and anti-hepatitis C virus status were also obtained before starting anti-TNF therapy. Patients with latent TB received rifampicin and isoniazid for 6 months, started simultaneously with anti-TNF therapy. Baseline assessment parameters included BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS), and NSAID consumption index.[15],[16],[17] These were repeated at 12 weeks, 24 weeks, 52 weeks, and 104 weeks after starting the treatment with Etacept and at 12 weeks and 24 weeks after starting treatment with Intacept. Other parameters assessed at above-mentioned time points included ASAS-20 (Assessment of SpA International Society), ASAS-40, and ASAS-partial remission (ASAS-PR).[18],[19] The primary endpoint was achievement of BASDAI <4 and secondary endpoints were achievement of ASAS 20, ASAS 40, and ASAS-PR responses. Patients were also advised physiotherapy in the form of spinal extension exercises, deep breathing exercises, and regular aerobic exercises such as brisk walk, cycling, and swimming. Etanercept biosimilar 50 mg was administered subcutaneously weekly for first 12 weeks. In the first 2 years starting from April 2013, we used only Etacept while afterward most new patients received Intacept when the latter became available. Patients initially treated with Etacept continued the same drug except when discontinuation was necessitated by inefficacy or adverse effect. Same was applicable in case of Intacept. Patients achieving “major improvement” after 12 weeks (as defined by ASAS i.e., reduction of ASDAS by >2 points) received same biosimilar every 2 weeks subsequently. The patients who failed to achieve “major improvement” at the end of 12 weeks were continued on weekly dose of prescribed biosimilar. They were then assessed at the end of 24 weeks for the achievement of “major improvement” and if achieved, were switched to once every 2 weeks dosages. In case of worsening of symptoms, patients were reverted to weekly regimen. Patients with lack of any response at 12 weeks discontinued the drug. Adverse effects of treatment were carefully noted. Patients who discontinued following up with rheumatology clinic were contacted telephonically and their missing data were received through E-mail or on next personal visit at clinic.

Ethical approval

The study protocol was approved by the Ethics Committee of our institution.


  Results Top


Patient characteristics

[Figure 1]a and [Figure 1]b give the outline of patients considered eligible for anti-TNF therapy. A total of 82 patients were started on etanercept biosimilar. Five patients had to be excluded due to discontinuation of treatment during first 12 weeks (3 had an adverse reaction and 2 decided to drop out because of fear of adverse effects). Thus, 77 patients continued the treatment (Etacept 54, Intacept 23). [Table 1] gives the baseline demographic characteristics of these patients.
Figure 1: (a) Outline of patient response in Etacept group. (b) Outline of patient response in Intacept group. *Depending on physician's evaluation and patient reported global assessment

Click here to view
Table 1: Baseline demographic characteristics of patients

Click here to view


Clinical efficacy

Both etanercept biosimilars provided excellent symptom relief in axial symptoms and in patients with psoriatic arthropathy. Response in peripheral arthritis and entheseal symptoms remained moderate.

Etacept

Details of clinical response are shown in [Figure 1]a. It is noteworthy that progressive improvement in all endpoints occurred over time with Etacept. [Figure 2] gives the graphical presentation of the trend of improvement. The primary endpoint was achieved by 77% (42/54) patients. [Table 2] gives serial outcomes, including achievement of secondary endpoints at various time intervals. After commencing Etacept, 10 out of 54 patients did not require any NSAID in first 3 months of therapy. Overall reduction of NSAID index can be observed in [Table 2]. As many as 43 patients had completed 52 weeks and 27 patients had completed 104 weeks. Twelve patients were able to maintain major improvement status on once a month dose of Etacept. Seven out of ten patients were able to discontinue oral corticosteroids. Three patients, who were unable to taper off steroids, had primary failure of Etacept. One patient had axial SpA with inflammatory bowel disease (IBD), in whom IBD was asymptomatic at the time of starting Etacept. His axial symptoms responded well with treatment without any recurrence of IBD-related symptoms during 2 years of follow-up. There were three patients who had only partial improvement at the end of 12 weeks. Although their BASDAI did not fall below four, their NSAID consumption index had dropped substantially. They were reluctant to discontinue the biosimilar for lack of a better alternative. Hence, we kept them in follow-up while continuing weekly dose of Etacept. At the end of 6 months, one of these three patients achieved “major improvement,” so he was switched to Etacept once every 2 weeks dosage. He remained well on the same dosage at the end of 1-year follow-up.
Figure 2: Graphical presentation of serial outcomes. (a) Trend of assessment of spondyloarthritis international society 20, assessment of spondyloarthritis international society 40, and assessment of spondyloarthritis international society partial remission response achievement. (b) Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Disease Activity Index, and nonsteroidal anti-inflammatory drug index trend for Etacept. (c) Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Disease Activity Index, and nonsteroidal anti-inflammatory drug index trend for Intacept

Click here to view
Table 2: Serial outcome profile of patients

Click here to view


Intacept

[Figure 1]b shows details of clinical response in Intacept group. The primary endpoint was achieved by 61% (14/23) patients. [Table 2] gives serial outcomes of various parameters over 24 weeks. Same is depicted in graphical manner in [Figure 2]. After starting Intacept, as many as eight patients were able to discontinue NSAIDs completely. Four out of five patients were able to taper off oral corticosteroids. One patient, who could not discontinue steroids, had primary failure of Intacept. There were two patients who had only partial improvement at the end of 12 weeks. Although their BASDAI did not fall below 4, they wished to continue the biosimilar for lack of a better alternative. Hence, they were kept in follow-up, while continuing weekly dose of Intacept. Although only short-term data were available for Intacept, the improvement trend appeared similar to that of Etacept.

Safety

Overall, injection site reactions were the most common adverse reactions followed by upper respiratory tract infections. In Etacept group, we noted injection site reactions (n = 9), upper respiratory tract infections (n = 4), skin and subcutaneous tissue infections (n = 2), recurrence of acute anterior uveitis (n = 1), episode of Vitritis (n = 1), reactivation of TB (n = 1), weight gain (n = 1), diarrhea (n = 1), and headache (n = 1). Four patients had to discontinue Etacept due to adverse events. In Intacept group, injection site reactions (n = 2), upper respiratory tract infections (n = 1), weight gain (n = 1), polycythemia (n = 1), hair fall (n = 1), and headache (n = 1) were observed. Two patients had to discontinue Intacept due to treatment emergent adverse events.

History of acute anterior uveitis was present in 11 patients in Etacept group and five patients in Intacept group, of whom only 1 had recurrence of uveitis (4 months after starting Etacept). Etacept was discontinued after recurrence of uveitis. His uveitis recovered completely with a short course of topical steroid therapy. One patient developed tuberculous pleural effusion after 31 months of Etacept therapy. His screening for latent TB was positive (Mantoux test > 20 mm) and he had received rifampicin and isoniazid as part of treatment of latent TB infection. Etacept was discontinued and full course of antitubercular therapy was administered, following which he completely recovered from tuberculosis.


  Discussion Top


This retrospective study in patients with active SpA shows that treatment with etanercept biosimilars is both efficacious and safe. Progressive improvement in terms of disease activity was observed over time. Most patients remained in a state of low disease activity during the study period. In addition, there was a significant improvement in BASFI score implying that a proportion of the functional loss in AS patients is reversible.

Murphy et al. showed that the efficacy of etanercept could be sustained even with reduced dosing frequency once a stable state of improvement was achieved.[20] Encouraged by this observation coupled with financial constraints in the Indian setting, we reduced the frequency of Etacept injections to once in 2 weeks after the first 12 weeks of treatment. The efficacy remained uncompromised in majority of patients during the entire follow-up. Intacept showed the same trend though only limited data are available till now. An open-label observational study by Brandt et al. on etanercept innovator product with once a week dosing reported ASAS 20 and ASAS 40 response at 54 weeks in 72.1% and 63.5% patients, respectively.[21] They also reported mean BASDAI value of 2.8 ± 2.3 at week 54. In our retrospective analysis, we obtained ASAS 20 and ASAS 40 response at 52 weeks in 81% and 56% patients, respectively. Mean BASDAI value at this time point was 2.5 ± 0.9. These results are comparable and their significance is increased by the fact that our patients received lower cumulative doses of the drug. The strategy of reducing the dosage frequency without loss of efficacy has implications on the cost of treatment as well. This is of special relevance in resource-constrained countries such as India, where most patients are neither covered by medical insurance nor supported by government or employer.

Overall, adverse event profile did not differ significantly from what is previously reported for the innovator product.[21] India has a relatively high prevalence of active and latent tuberculosis as compared to developed countries.[22] Reduced dosing frequency may also bring down the risk of reactivation of latent tuberculosis in our patients. This has already been noted in the case of infliximab treatment of spondyloarthropathy.[23] The lone patient who developed tuberculous pleural effusion after 31 months of Etacept therapy in the present study had already received 6 months course of rifampicin and isoniazid for his latent TB at the start of anti-TNF therapy. The reason for TB in his case may be a new exposure to TB. Good response to first-line antitubercular drugs rules out any possibility of drug-resistant TB. This case also demonstrates the ever persisting possibility of developing TB in patients receiving anti-TNF drugs in high TB burden countries despite initial treatment of latent TB.

Most experts advise that antitubercular therapy (ATT) should be started at least 1 month before the commencement of anti-TNF therapy if latent TB is present.[24] In the present study, we started ATT and etanercept biosimilar at the same time without any adverse consequence. This is consistent with an earlier observation that etanercept does not cause reactivation tuberculosis in the first 6 months of therapy.[25]

Although the prevalence of latent TB infection identified by standard Mantoux positivity in India is 44%, we found Mantoux positivity rate of 27% only in patients with SpA in this study.[22] This may be due to the phenomenon of anergy in rheumatic diseases. It is interesting to note that no Mantoux negative patient developed reactivation TB. Probably, the interferon gamma release assay adequately compensated for the diagnostic gap resulting from tuberculin anergy.

Acute anterior uveitis as a potential side effect of etanercept which is already well documented in literature.[26],[27],[28],[29] In this retrospective report, we had prescribed Etacept to 11 patients and Intacept to five patients, who already had a history of acute anterior uveitis. Discontinuation of Etacept was required in one patient, who developed unilateral acute anterior uveitis after first 4 months of treatment. He was receiving Etacept once every week. All other patients receiving Etacept or Intacept could continue treatment without any further episodes of uveitis. No patient had developed a new-onset acute anterior uveitis while on etanercept biosimilar therapy. We hypothesize that reducing the dosage frequency might have impact on reducing the incidence of attacks of uveitis.

Limitations of this study include its retrospective design, absence of control group to compare the results, 104-week follow-up only on 27 patients in Etacept group, and small sample size of Intacept group (as Intacept was introduced in Indian market much later). We did not do a formal cost-benefit analysis to obtain an estimate of the economic impact of biosimilar therapy. Further studies addressing these limitations are necessary. Despite these limitations, overall data show encouraging results on efficacy and safety of both the biosimilars.

The etanercept biosimilars were generally well tolerated in this study, with no unexpected safety issues in either group. The overall efficacy profile was comparable to that of the innovator product. The strategy of reduced dosing frequency following initial 12 weeks of standard regimen did not result in any loss of efficacy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Poddubnyy D. Axial spondyloarthritis: Is there a treatment of choice? Ther Adv Musculoskelet Dis 2013;5:45-54.  Back to cited text no. 1
    
2.
Braun J, Sieper J. Therapy of ankylosing spondylitis and other spondyloarthritides: Established medical treatment, anti-TNF-alpha therapy and other novel approaches. Arthritis Res 2002;4:307-21.  Back to cited text no. 2
    
3.
Gran JT, Skomsvoll JF. The outcome of ankylosing spondylitis: A study of 100 patients. Br J Rheumatol 1997;36:766-71.  Back to cited text no. 3
    
4.
Barlow JH, Wright CC, Williams B, Keat A. Work disability among people with ankylosing spondylitis. Arthritis Rheum 2001;45:424-9.  Back to cited text no. 4
    
5.
Ward MM. Functional disability predicts total costs in patients with ankylosing spondylitis. Arthritis Rheum 2002;46:223-31.  Back to cited text no. 5
    
6.
Grom AA, Murray KJ, Luyrink L, Emery H, Passo MH, Glass DN, et al. Patterns of expression of tumor necrosis factor alpha, tumor necrosis factor beta, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy. Arthritis Rheum 1996;39:1703-10.  Back to cited text no. 6
    
7.
Boonen A. Socioeconomic consequences of ankylosing spondylitis. Clin Exp Rheumatol 2002;20 6 Suppl 28:S23-6.  Back to cited text no. 7
    
8.
van der Heijde D, Sieper J, Maksymowych WP, Dougados M, Burgos-Vargas R, Landewé R, et al. 2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann Rheum Dis 2011;70:905-8.  Back to cited text no. 8
    
9.
Davis JC, van der Heijde DM, Braun J, Dougados M, Cush J, Clegg D, et al. Sustained durability and tolerability of etanercept in ankylosing spondylitis for 96 weeks. Ann Rheum Dis 2005;64:1557-62.  Back to cited text no. 9
    
10.
Inman RD, Davis JC Jr., Heijde Dv, Diekman L, Sieper J, Kim SI, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: Results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum 2008;58:3402-12.  Back to cited text no. 10
    
11.
van der Heijde D, Dijkmans B, Geusens P, Sieper J, DeWoody K, Williamson P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: Results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 2005;52:582-91.  Back to cited text no. 11
    
12.
van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: Results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2006;54:2136-46.  Back to cited text no. 12
    
13.
European Medicines Agency. Guideline on similar biological medicinal products. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/general/general_content_001832.jsp. [Last cited on 2014 Dec 15].  Back to cited text no. 13
    
14.
Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: The Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994;21:2286-91.  Back to cited text no. 14
    
15.
Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, et al. Anew approach to defining functional ability in ankylosing spondylitis: The development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994;21:2281-5.  Back to cited text no. 15
    
16.
Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:18-24.  Back to cited text no. 16
    
17.
Dougados M, Simon P, Braun J, Burgos-Vargas R, Maksymowych WP, Sieper J, et al. ASAS recommendations for collecting, analysing and reporting NSAID intake in clinical trials/epidemiological studies in axial spondyloarthritis. Ann Rheum Dis 2011;70:249-51.  Back to cited text no. 17
    
18.
Brandt J, Listing J, Sieper J, Rudwaleit M, van der Heijde D, Braun J. Development and preselection of criteria for short term improvement after anti-TNF alpha treatment in ankylosing spondylitis. Ann Rheum Dis 2004;63:1438-44.  Back to cited text no. 18
    
19.
Zochling J, van der Heijde D, Burgos-Vargas R, Collantes E, Davis JC Jr., Dijkmans B, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2006;65:442-52.  Back to cited text no. 19
    
20.
Murphy CL, Awan S, Sullivan MO, Chavrimootoo S, Bannon C, Martin L, et al. Major cost savings associated with biologic dose reduction in patients with inflammatory arthritis. Ir Med J 2015;108:19-21.  Back to cited text no. 20
    
21.
Brandt J, Listing J, Haibel H, Sörensen H, Schwebig A, Rudwaleit M, et al. Long-term efficacy and safety of etanercept after readministration in patients with active ankylosing spondylitis. Rheumatology (Oxford) 2005;44:342-8.  Back to cited text no. 21
    
22.
Indian Council of Medical Research Tuberculosis in India: Anational Sample Survey 1955-1958. Technical Report Series, New Delhi, India; 1959.  Back to cited text no. 22
    
23.
Kumar A. Experience with anti-tumor necrosis factor-a therapy in India. APLAR J Rheumatol 2006;9:136-41.  Back to cited text no. 23
    
24.
Theis VS, Rhodes JM. Review article: Minimizing tuberculosis during anti-tumour necrosis factor-alpha treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2008;27:19-30.  Back to cited text no. 24
    
25.
Misra R, Amin S, Joshi VR, Rao UR, Aggarwal A, Fatima F, et al. Open lable evaluation of the efficacy and safety of etanercept in rheumatoid arthritis. J Indian Rheumatol Assoc 2005;13:131-4.  Back to cited text no. 25
    
26.
Cobo-Ibáñez T, del Carmen Ordóñez M, Muñoz-Fernández S, Madero-Prado R, Martín-Mola E. Do TNF-blockers reduce or induce uveitis? Rheumatology (Oxford) 2008;47:731-2.  Back to cited text no. 26
    
27.
Rudwaleit M, Rødevand E, Holck P, Vanhoof J, Kron M, Kary S, et al. Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: Results of a prospective open-label study. Ann Rheum Dis 2009;68:696-701.  Back to cited text no. 27
    
28.
Sieper J, Koenig A, Baumgartner S, Wishneski C, Foehl J, Vlahos B, et al. Analysis of uveitis rates across all etanercept ankylosing spondylitis clinical trials. Ann Rheum Dis 2010;69:226-9.  Back to cited text no. 28
    
29.
Lim LL, Fraunfelder FW, Rosenbaum JT. Do tumor necrosis factor inhibitors cause uveitis? A registry-based study. Arthritis Rheum 2007;56:3248-52.  Back to cited text no. 29
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Methods
Results
Discussion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed1502    
    Printed21    
    Emailed0    
    PDF Downloaded200    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]