Real-life Tolerability and Effectiveness of Adalimumab Biosimilar in Ankylosing Spondylitis: the Adalimumab Biosimilar Patient Registry Data.

OBJECTIVE: Adalimumab is a well-established anti-tumor necrosis factor therapy for patients with ankylosing spondylitis (AS). An indigenously developed biosimilar adalimumab (bADA) (ZRC-3197; Exemptia) is approved for prescribing in India. In this article, we present the effectiveness and tolerability of this bADA in real-life Indian patients with AS from the Adalimumab Biosimilar Patient Registry (ASPIRE) (ISRCTN: 16838474). METHODS: ASPIRE is a postmarketing observational registry for evaluating the real-world experiences of patients with autoimmune inflammatory disorders across multiple centers in India who were prescribed 40 mg of Exemptia subcutaneously every fortnight. For this report, data available until 24 weeks of bADA treatment for patients with AS who were included in the registry were evaluated. RESULTS: Data from 308 patients with AS from the registry (median age of 35.0 [range 17-68] years, 19% women) were analyzed. In analyzable patients with complete data, there was a gradual and significant decrease (P < 0.001) in the primary disease outcome scores (the mean Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] score [n = 107] improved from 6.2 ± 1.54 to 2.1 ± 0.64, and the median visual analogue scale [VAS] score [n = 101] improved from 8 to 2) after 24 weeks of bADA therapy. BASDAI score was lower than 4 in about 94% of patients after 24 weeks of therapy, and 95% of patients achieved BASDAI50 response. The overall global assessment for efficacy and tolerability was 'good' to 'excellent' for a majority of the patients (≥98%), as rated by physicians as well as patients. The therapy was tolerated well, and there were no new unexpected adverse reactions with the biosimilar's use during this study. CONCLUSION: This report demonstrates the tolerability and effectiveness of bADA (Exemptia) after its clinical use for 24 weeks in real-world patients with AS from Indian clinical practice.

Recent Advances in Idiopathic Inflammatory Myopathies (IIM) - Rapid Discoveries of Myositis-specific Antibodies (MSAS) and Myositis-Associated Antibodies (MAAS) - Moving Towards 'Precision Medicine'.

The progress in the understanding of inflammatory muscle diseases over the past several decades has been slow but steady. The classification given by Bohan and Peter's in 1975 was based on clinical features. It served well, but inadequacies were also obvious. The increasing discoveries of autoantibodies in this group of disorders have helped in refining the classification of Bohan and Peter's to a large extent. At the present state of knowledge, it is now possible to classify and sub-classify this group of diseases using distinct clinical features combined with the type of autoantibodies in well-defined subsets. Not only the subsets help predicting the type of organ involvement and comorbidities but may also help choose a specific drug for a particular subclass. This approach may lead to the practice of precision medicine for inflammatory myositis.

Real-Life Tolerability and Effectiveness of Adalimumab Biosimilar in Rheumatoid Arthritis: ASPIRE Registry Data.

INTRODUCTION: The TNF-α blocker adalimumab is a well-proven therapy for rheumatoid arthritis (RA). A biosimilar adalimumab (ZRC-3197; Exemptia™), a 'fingerprint match' to reference adalimumab, has been approved for prescription in India since 2014. Here, we report on the effectiveness and tolerability of this biosimilar adalimumab (bADA) from the Adalimumab Biosimilar Patient Registry [ASPIRE; ISRCTN16838474], which contains data from real-life RA patients from India. METHODS: ASPIRE is a post-marketing, observational registry that evaluates real-world experience across multiple centres in India. Patients with moderate to severe RA who were prescribed bADA 40 mg subcutaneously every fortnight were enrolled. Patients with complete data available until 24 weeks of bADA treatment were extracted and analyzed for standard disease activity measures and reported adverse events. RESULTS: The registry included 149 patients with RA who had a median age of 41 (22-67) years; 65% of the patients were female. Disease outcome measures, i.e. ESR, DAS-ESR and VAS-pain scores, showed gradual and significant decreases (p < 0.0001 for all) in 73 analyzable patients who received 24 weeks of bADA therapy. ACR20, ACR50 and ACR70 responses were achieved in 48%, 48% and 34% of patients after 24 weeks of therapy, respectively, and about 58% and 15% of patients were moderate and good EULAR responders, respectively. Physician and patient ratings for the overall global assessment of efficacy and tolerability were 'good' to 'excellent' for the majority of the patients (≥ 96%). No new safety signals were observed when analyzing this registry data. CONCLUSION: Real-life data from this post-marketing observational analysis demonstrate the clinical effectiveness and tolerability of 24 weeks of adalimumab biosimilar therapy in Indian patients with RA. This report also reflects upon the treatment strategies and prescription patterns for such therapies in Indian clinical practice. TRIAL REGISTRATION: ISRCTN16838474. FUNDING: Cadila Healthcare Limited, India.

Screening for latent tuberculosis infection among patients with rheumatoid arthritis in the era of biologics and targeted synthetic disease-modifying anti-rheumatic drugs in India, a high-burden TB country: The importance of Mantoux and Quantiferon-TB Gold tests.

AIM: To test the validity of an augmented tuberculosis skin test (a-TST) combined with Quantiferon TB-gold® (QFTG) test for the screening of latent tuberculosis infection (LTBI) in patients with rheumatoid arthritis (RA) being considered for treatment with biologic disease-modifying anti-rheumatic drugs or targeted synthetic disease-modifying anti-rheumatic drugs. METHOD: Standard TST using 1 tuberculin unit (TU) of purified protein derivative (PPD, RT23 strain) was carried out. If the positivity was less as compared to the general population, then a-TST using 10 TU PPD was employed. Simultaneously, QFTG test was also performed. RESULTS: Using standard TST, 6/44 (13.6%), patients were positive compared to the reported figures of ~ 40% of the general population; 38 of the remaining TST-negative patients were then given an a-TST with 10 TU PPD; eight of them dropped out. Of the remaining 30 patients, eight (26.6%) were positive. Another 70 patients tested directly with a-TST; 22 (31.4%) were found positive. Thus, of a total of 100 patients tested with a-TST, 30 (30%) were positive. In 54 a-TST negative patients, QFTG was done; seven (13%) were positive. Thus, in combined a-TST with QFTG, 43% of the RA patients were found positive, suggestive of the presence of LTBI. CONCLUSION: Combined a-TST with QFTG testing gave 43% positivity among RA patients, which is close to the reported ~ 40% Mantoux positivity in the general population. Therefore, this method for the screening of LTBI in Indian patients with RA being considered for tumor necrosis factor alpha treatment could be satisfactory for offsetting TB flare. It may apply to other high-burden TB countries around the world.

Switching from Other Biologics to ZRC3197 (Adalimumab Biosimilar) in Patients with Spondyloarthropathy: A Prospective Evaluation from Real-Life Clinical Practice.

Tumour necrosis factor inhibitors (TNFi) like Infliximab, Etarnacept and Adalimumab have been successfully studied in controlled clinical trials and are currently recommended in the treatment of patients with spondyloarthropathy (SPA). Significant proportion of patients in clinical studies have, however, failed to achieve a desired clinical response, or, are discontinued from the therapy due to secondary inefficacy or side effects. Therefore, owing to the different molecular structures and routes of administration, switching from one TNFi to another is considered as in important option in SPA patients eligible to receive TNFi therapy. We report here our experience of switching Indian patients with SPA with inadequate response to other TNFi to ZRC 3197(Adalimumab Biosimilar) treatment available in India.

Tuberculosis and biologics in rheumatology: A special situation.

India has a huge patient burden of rheumatic diseases (RDs) including rheumatoid arthritis. The use of biologics has transformed the treatment paradigm for RD; however, biologic treatment-related infections (especially tuberculosis [TB]) are an area of potential concern for TB-endemic nations like India. Anti-tumor necrosis factor (TNF) therapy impairs the physiological TNF-mediated signaling and may cause reactivation and dissemination of latent TB infection (LTBI). Careful screening is, thus, crucial in RD patients who are about to commence anti-TNF treatment. To date, there is no consensus available for the screening, evaluation and treatment of LTBI as well as on the drug dosage and duration regimen (monotherapy or combination therapy) in the Indian population. An evidence-based algorithm for LTBI screening and management in RD patients undergoing biologic disease-modifying anti-rheumatic drug therapy is suggested in this review for Indian rheumatologists. The proposed algorithm guides physicians through a step-wise screening approach, including medical history, tuberculin skin test, interferon gamma release assay, chest radiograph and management of LTBI with isoniazid therapy or its combination with rifampicin. Further, the provided algorithm can aid the national bodies (such as National TB Control Program) in formulating recommendations for LTBI in this high-risk population.

Cost-effective use of investigations in developing countries.

In recent years, the cost of health care around the world has risen at a rate that is deemed unsustainable. It has been estimated that 20% of this could be saved by rationalising laboratory investigations and reducing inappropriate requisitioning of the investigations. There are several reasons for the excessive, redundant, inappropriate or unnecessary investigations and procedures, which in some instances are unethical practices. The impact in financial terms is more in developing countries such as India with <5% of the population having medical insurance and hardly any other third-party payer system. The 'Choosing Wisely' campaign of the American Board of Internal Medicine, Canadian Rheumatology Association's Choosing Wisely Committee and the 'Society for Less Investigative Medicine' (SLIM) initiative of the doctors of All-India Institute of Medical Sciences (AIIMS), New Delhi, all have provided recommendations to reduce unnecessary investigations, and these are among some of the efforts to reduce the cost of investigations without compromising the quality of care.

Acute inflammatory ankle arthritis in northern India--Löfgren's syndrome or Poncet's disease?

OBJECTIVES: To analyse patients presenting with acute inflammatory ankle arthritis from an aetiological standpoint; whether they had Löfgren's syndrome (acute presentation of sarcoidosis), or Poncet's disease (reactive arthritis due to tuberculosis infection). An additional objective was to establish a simple, practical yet optimal algorithm for diagnostic approach and management of such patients. METHODS: The study included 18 patients from northern India presenting with isolated acute inflammatory ankle arthritis. A combination of complete clinical evaluation, Mantoux test and contrast-enhanced computerised tomography (CE-CT) of the chest was carried out and results analysed. RESULTS: Among 18 patients presenting as inflammatory ankle arthritis is was possible to classify 10 of them as Löfgren's syndrome all of whom had negative Mantoux test and bilateral hilar lymphadenopathy without central necrosis. The other 8 patients could be classified as Poncet's disease as all of them had positive Mantoux test and showed mediastinal lymphadenopathy with or without unilateral hilar lymph nodes, with central necrosis. Finally, appropriate drug treatment (glucocorticoids with glucocorticoid-sparing drugs methotrexate and hydroxychloroquine in patients with Löfgren's syndrome; standard anti-tuberculosis drugs in Poncet's disease) gave excellent clinical response and patients remained well over a period of 1 year of follow-up. CONCLUSION: Investigated on standard lines without any invasive procedure, patients with isolated inflammatory ankle arthritis could be classified in 2 distinct categories namely: (1) Löfgren's syndrome in its complete (with EN) or incomplete (without EN) form; (2) Poncet's disease. Appropriate treatment gave satisfactory response and patients remained well over a period of 1 year of follow-up.

Acute abdomen in SLE.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune connective tissue disease with protean manifestations. Most often it presents with mucocutaneous, musculoskeletal or renal involvement. In comparison, gastrointestinal (GI) manifestations of SLE are far less common. The case presented here highlights the differential diagnosis of GI manifestations of SLE that range from non-life-threatening to serious life-threatening complications, including some of the complications of on-going drug treatments. While some of them present as 'acute abdomen', others are more subacute or chronic, yet serious enough to be life-threatening. The serious GI manifestations of SLE include mesenteric vasculitis causing perforation or hemorrhage with peritonitis, acute pancreatitis and intestinal pseudo-obstruction. The patient in this paper had clinical features, imaging findings and laboratory parameters that helped the treating physician to narrow down the diagnostic possibilities and finally, in making the diagnosis of lupus-pancreatitis. She was treated with intravenous 'bolus' (i.v.-pulse) methylprednisolone for 3 days, i.v.-pulse cyclophosphamide 750 mg (one dose) along with oral methylprednisolone and other supportive measures including blood transfusions. This led to prompt and complete recovery.

Low-dose and high-dose methotrexate are two different drugs in practical terms.

Methotrexate (MTX) was originally synthesised as an anti-cancer drug. Soon it was also used in immunoinflammatory diseases, mainly in the field of rheumatology. However, the dose used in oncology is several-fold higher as compared to the dose used in systemic immunoinflammatory rheumatological diseases. This led to the use of terms 'low-dose MTX' (LD-MTX) and 'high-dose MTX' (HD-MTX) respectively for its use in immunoinflammatory rheumatological diseases as against its use in oncology. Extensive studies have demonstrated that therapeutic action, clinical indications, adverse effects and mechanisms of action of LD-MTX and HD-MTX are quite different. It is somewhat akin to low-dose aspirin versus high-dose aspirin with entirely different spectra of therapeutic action and adverse effects. It is important to understand this difference. This would help in allaying unfounded fear of adverse effects of LD-MTX that is often mistakenly considered the same as that of HD-MTX used in oncology.

Vertebral sarcoid mimicking ankylosing spondylitis or just a co-incidence?

OBJECTIVE: To illustrate that among the protean musculoskeletal manifestations of sarcoidosis back pain that could mimic inflammatory back pain of ankylosing spondylitis (AS), should also be considered. METHOD: A case report of a HLA B27 negative patient with classical features of inflammatory back pain that was initially diagnosed as AS is being presented. He showed poor response to standard treatment with nonsteroidal anti-inflammatory drugs and physiotherapy exercises with increasing symptoms of pain, stiffness and development of typical posture of AS. Spine and sacroiliac joint imaging showed progressive features of AS. He was considered a candidate for tumour necrosis factor-alpha inhibitor (iTNF-alpha) infliximab therapy and, therefore, screened for latent tuberculosis using Mantoux test (MT), QuantiFerron-TB Gold (QTG) test and imaging of the chest. Although MT and QTG were negative, contrast-enhanced computerised tomography (CE-CT) of the thorax showed significant hilar and mediastinal lymph nodes (LN). RESULT: Biopsy of the mediastinal LN showed non-caseating granulomas typical of sarcoidosis. He was then given infliximab to which he responded dramatically. CONCLUSION: The question remains whether he is a patient with vertebral sarcoidosis or it is a simple coincidence of two unrelated diseases appearing togeth r in this person.

Preventing tuberculosis flare in patients with inflammatory rheumatic diseases receiving tumor necrosis factor-alpha inhibitors in India -- An audit report.

OBJECTIVE: To test the efficacies of a strategy for preventing tuberculosis (TB) in Indian patients with inflammatory rheumatic diseases (IRD) treated with tumor necrosis factor-alpha (TNF-alpha) inhibitor. METHODS: The screening strategy included tuberculosis skin test (TST), QuantiFERON-TB Gold (QTG) test, standard chest radiograph, and contrast enhanced-computerized tomography of the chest (CT). RESULTS: Among 53 patients screened, 17 (32%) had >or= 1 test positive, with 5 (9.4%) patients having TB infection (clinical, CT, biopsy). The remaining 12 patients showed latent TB; 1 additional patient with negative screening tests was diagnosed with latent TB retrospectively for he developed TB disease within a few weeks of receiving infliximab. The remaining 35 patients tested negative with all tests. The combination of 4 screening tests gave a sensitivity of 0.83, specificity of 0.74, positive predictive value (PPV) 0.29, and negative predictive value (NPV) 0.97. Only 22 patients could afford treatment with TNF-alpha inhibitors; 19 of them were negative in the screening tests. Three patients who were positive on TST and/or QTG received prophylactic treatment with TNF-alpha inhibitor. Since implementation of the screening strategy, only 1 of 22 (4.5%) patients given TNF-alpha inhibitor developed probable TB disease. CONCLUSION: With the use of these 4 TB screening tests in India, where TB is highly prevalent, TB could be excluded with a high degree of certainty (NPV 0.97). However, as even this combination of tests has only moderate sensitivity and specificity and poor PPV for detecting TB, vigilance may be advisable even if only one of the tests is positive.