Ragini Srivastava

Efficacy and safety of hydroxychloroquine sulphate in rheumatoid arthritis: a randomized, double-blind, placebo controlled clinical trial--an Indian experience.

ABSTRACT Objective: Hydroxychloroquine (HCQ) has been used for a long time worldwide as a therapy for rheumatoid arthritis (RA). This trial was designed to determine whether HCQ was efficacious and safe in Indian patients with RA. Research design and methods: The trial was a multicentre, placebo controlled, randomized and double-blind study. One hundred and twenty-two patients with RA were enrolled in 3 different centres for the trial (26 males and 96 females in the age group of 18–60 years). Patients were randomized to receive either hydroxychloroquine tablets (n = 61) two tablets of 200 mg daily or placebo (n = 61) two tablets daily. After 8 weeks all patients received one tablet of hydroxychloroquine 200 mg daily for 4 weeks. Every patient also received one tablet of Nimesulide 100 mg twice daily. Main outcome measures: Assessment of response at 12 weeks using modified ACR 20 (American College of Rheumatology 20) criteria where Health Assessment Questionnaire (HAQ) was replaced by ARA (American Rheumatology Association) functional class. Results: 40.4% of patients on hydroxychloroquine showed improvement by modified ACR response criteria whereas only 20.7% ( p = 0.02) showed improvement in the placebo group. No significant side effects were observed in any of the patients. There were no ocular toxicities. Conclusions: Hydroxychloroquine was found to be an effective and well-tolerated drug in rheumatoid arthritis in Indian patients.

Oral Methotrexate in split dose weekly versus oral or parenteral Methotrexate once weekly in Rheumatoid Arthritis: a short‐term study

To investigate whether methotrexate (MTX) administered orally to rheumatoid arthritis (RA) patients in split doses at 2–3 days’ interval, would result in equal or better efficacy, tolerability and compliance, without increasing toxicity compared to single weekly dose given orally or parenterally.

Steroids Decrease Prevalence of Positive Tuberculin Skin Test in Rheumatoid Arthritis: Implications on Anti-TNF Therapies

Tuberculin skin test has been used as an indicator of latent tuberculosis in patients with Rheumatoid Arthritis (RA) before administration of biologicals. Effect of Disease modifying antirheumatic drugs (DMARDs) and steroids on the result of tuberculin skin test (TST) may have important implications in interpretation of results of this test. Objectives. To find the prevalence of positive TST in rheumatoid patients and the effect of standard treatment on the results of TST. Method. In this cross-sectional study two hundred and fifty patients of RA above 18 years of age, classified using 1987 ACR criteria for RA, were enrolled from rheumatology outdoor. Demographics, disease activity, disease duration, and therapy were recorded. All patients underwent TST. Results. Fifty-one (20.4%) patients were found to be tuberculin positive. Tuberculin positivity was not affected by MTX intake but it was significantly low in patients with recent steroid intake as compared to patients who had not taken steroids in last 3 months (3% versus 25%, P = 0.002). Conclusion. Prevalence of tuberculin positivity in patients with RA was found to be low. Results were not affected by methotrexate; however tuberculin skin test results in patients with recent use of steroids are likely to be negative.

Prevalence of rheumatic musculoskeletal symptoms in rural and urban areas : a cross-sectional study in northern India

To study the prevalence of rheumatic musculoskeletal symptoms in rural and urban areas of Lucknow.

Current biological understanding and futuristic views for osteoarthritis treatment: Optimistic or otherwise?

Osteoarthritis (OA) was considered to be a non-inflammatory disease by us in the 1980s, as most rheumatologists would do. Managing an inflamed unilateral knee otherwise showing clinical and radiological features of OA was a great dilemma. By the early 1990s, we were convinced about the presence of inflammation in patients with OA, at least in a subset of patients. Evidence for the same has grown over the years and today OA is unequivocally considered to be an inflammatory disease. It is, therefore, no wonder that the current treatment approach in osteoarthritis is largely aimed at controlling inflammation. Agents believed to be effective in OA, for example intra-articular (IA) steroids, glucosamine sulphate, chondroitin sulphate, IA hyaluronan and diacerein are also known to have some anti-inflammatory properties. This issue of the Journal carries a number of papers on OA, including an interesting trial by Maghsoumi-Norouzabad et al. on the anti-inflammatory nature of Burdock root tea in patients with knee OA. Evidence has also emerged that the age-old drug of choice in OA, namely paracetamol / acetaminophen is often ineffective for pain relief in patients with OA. There is a paradigm shift in OA management from the existing penchant on providing “pain relief until the patient goes in for joint replacement” to exploring treatment options toward a possible cure or prevention of disease progression at an early phase. The behemoth of inflammation in OA is complex and difficult to tackle. Figure 1 is a simplification of a complex pathway. The inflammatory pathway can be divided roughly into three areas. The early pathway that incites inflammation, the amplificatory pathway and the end effector pathway. The end effector pathways are no different from any other inflammation. Hence medicines like non-steroidal anti-inflammatories (NSAIDs) and corticosteroids acting at these levels may not be different. The end pathway also includes the role of matrix metallo-proteinases (MMPs) and other substances responsible for inflammation and damage to cartilage as well as other joint tissue. This pathway is being tackled to produce new kinds of anti-inflammatory drugs that may also inhibit joint damage. Attempts toward development of agonists of tissue inhibitors of metalloproteinases (TIMP 3) or non-specific MMP antagonists have not yielded much success, but continue to be important therapeutic targets. Doxycycline, a non-specific inhibitor of MMPs, has been shown to slow progression of OA without symptomatic benefit. Inhibitors of MMP 13 have also been formulated and show great promise. Similarly, attempts are being made to find suitable products that inhibit “inducible nitric oxide synthesases” (iNOS) and aggrecanases, also known as, “A disintegrin and metalloproteinase with thrombospondin motifs” (ADAMTS) – in particular ADAMTS4 and ADMTS5. What is different in the OA inflammatory circuit? Early incitatory pathways and the amplificatory pathways are the steps different in OA as compared to classical immuno-inflammatory, autoimmune systemic diseases. The amplificatory pathway in OA is believed to involve the activation of NALP3 (NACHT, LRR and PYD domains containing Protein 3) inflammasome leading to release of caspase 1, also known as ProIL1 beta converting enzyme. This converts ProIL1 beta into active IL1 beta, thereby causing amplification of the inflammatory response. This activation of NALP3 inflammasome is comparable to activation of this pathway in familial Mediterranean fever (FMF). While mutated pyrin is responsible for activation of NALP3 inflammasome in FMF, inflammasome activation in OA requires an initiatory stimulus or the incitatory pathway. Since the NALP3 inflammasome is activated in OA similar to that in FMF, drugs that block inflammasome activation and those useful in FMF may also be useful in OA. Way back in 2002, use of colchicine in OA was reported by us and currently a trial on colchicine in OA is underway in Singapore. Colchicine has also been shown to suppress IL1 beta production in patients with gout. Similarly, other drugs used for FMF may also be useful for OA. Tumor necrosis factor (TNF)-a inhibitors (etanercept, infliximab), IL-1 trap

X-ray Knee as a Screening Tool for Osteoporosis

Cortical thickness (Cor-Th) of tibia varies considerably on X-ray knees. It was hypothesized that Cor-Th can be used for preliminary prediction of BMD. Ninety nine patients underwent a digital X-ray left knee fixed flexion PA view with an external calibration scale attached to X-ray plate and BMD by DXA using GE lunar machine (Madison, Wisconsin.). Cor-Th was measured at 5 selected levels (A,B,C,D, and E) ranging from 5-7 cm below the tibial plateau on its medial aspect. T-scores were recorded for BMD at AP spine, left forearm and left femur. Cor-Th of tibia at each level significantly correlated with each site of BMD measurement namely AP spine, left femur and left forearm. This correlation varied in the range from 0.241 to 0.426. For AP spine, it was maximum at level C (r=0.347, p<0.001) whereas for left femur and forearm sites, it was maximum at level B (r=0.426 &r=0.373 respectively, p<0.001). The correlation of Cor-Th with BMD varied with age. Above 56 years of age, Cor-Th at each level significantly correlated to BMD at each site. Medial tibial cortical thickness, 6 cm (level C) below tibial plateau can be used as preliminary predictor of patients who need a DXA scan.

Performances of Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) appear to be better than the gold standard Disease Assessment Score (DAS‐28‐CRP) to assess rheumatoid arthritis patients

To compare the performance of Disease Assessment Score of 28 joints – C‐reactive protein (DAS‐28‐CRP), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) composite measures to assess status of patients with rheumatoid arthritis (RA) on methotrexate, versus DAS‐28 CRP as the gold standard.