Publications by authors named "Shefali Khanna Sharma"

17 Publications

  • Page 1 of 1

Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial.

Ann Rheum Dis 2021 Jun 10. Epub 2021 Jun 10.

Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Objectives: There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX.

Methods: This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat.

Results: 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen.

Conclusion: A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially.

Trial Registration Number: CTRI/2018/12/016549.
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http://dx.doi.org/10.1136/annrheumdis-2021-220512DOI Listing
June 2021

Tocilizumab in COVID-19: finding the optimal route and dose.

Lancet Rheumatol 2020 Dec 17;2(12):e738-e739. Epub 2020 Sep 17.

Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.

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http://dx.doi.org/10.1016/S2665-9913(20)30334-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498201PMC
December 2020

Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study.

Arthritis Res Ther 2020 08 14;22(1):189. Epub 2020 Aug 14.

Clinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Ovarian toxicity is a dreaded complication of cyclophosphamide (CYC). With the use of lower cumulative doses of intravenous CYC (modified NIH regimens) and availability of better markers of ovarian toxicity, the incidence of ovarian dysfunction needs reassessment. Lupus disease activity, by itself, is also believed to affect ovarian function negatively.

Methods: This single-centre prospective cohort study recruited 50 female patients of severe lupus aged 18-40 years. Twenty-five patients each received induction with either monthly intravenous CYC (0.5-0.75 g/m) for 6-9 months or daily oral mycophenolate mofetil (MMF). Details of menstrual irregularities; serum levels of FSH, LH, estradiol, AMH, and inhibin B; and sonographic assessment of ovarian volume and antral follicular count were done at baseline and 6 months after treatment. Amenorrhoeic patients were re-evaluated at 1 year.

Results: Mean (SD) age of subjects in the CYC and MMF groups was 31.4 (6.3) and 28.4 (4.4) years, respectively. Mean (SD) SLEDAI at the initiation of therapy was 7.2 (2.5) in the CYC group and 5.8 (3.4) in the MMF group. The mean cumulative dose of CYC used was 4.6 (1.8) g. Three patients in the CYC group (versus none in MMF) had amenorrhoea at 6 months-two of these regained menses within 6 months, while only one (4%) developed sustained amenorrhoea (lasting more than 12 months) at 41 years of age, likely menopause. Serum FSH levels increased (p = 0.03), while AMH (p = 0.002) and inhibin B (p < 0.001) levels decreased significantly with 6 months of CYC therapy. Ovarian volume also reduced significantly (p = 0.005) with 6 months of CYC therapy, while antral follicular count reduced numerically (p = 0.32). Levels of AMH, inhibin-B, estradiol, ovarian volume, and antral follicular count after 6 months therapy were significantly lesser in the CYC group compared to the MMF group, despite being similar before the start of therapy.

Conclusions: Ovarian dysfunction with monthly intravenous CYC (modified NIH regimen) was predominantly subclinical, with a negative effect on ovarian reserve. No premature ovarian failure was noted at 1 year. No ovarian dysfunction occurred in the MMF group, despite having patients with severe background lupus. Use of intravenous CYC for induction may thus not be restricted in young lupus females with incomplete families for fear of gonadotoxicity, especially in life- or organ-threatening situations, where the benefits outweigh this subclinical risk.
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http://dx.doi.org/10.1186/s13075-020-02292-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429750PMC
August 2020

Rational use of tocilizumab in COVID-19.

Ann Rheum Dis 2020 Jul 31. Epub 2020 Jul 31.

Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India

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http://dx.doi.org/10.1136/annrheumdis-2020-218519DOI Listing
July 2020

Efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease-a randomised controlled trial.

Rheumatol Int 2020 May 1;40(5):703-710. Epub 2020 Apr 1.

Post Graduate Institute of Medical Education and Research, Chandigarh, India.

To assess the efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease (SSc-ILD). This was a double-blind, randomised, placebo-controlled, pilot study. Subjects with SSc-ILD and forced vital capacity (FVC) between 50 and 80% of the predicted (%pred) value were randomised in 1:1 ratio to receive either pirfenidone (2400 mg/day) or placebo for 6 months. Primary outcome was the proportion of subjects with either stabilisation or improvement in FVC at 6 months. Secondary outcomes were the absolute change in the %pred FVC, Mahler's dyspnoea index, 6-min walk distance (6MWD), modified Rodnan skin score (MRSS) and serum levels of tumour necrosis factor α (TNF-α) and transforming growth factor β (TGF-β). Thirty-four subjects with median (range) age of 41 (20-63) years (91.2% women) and median (range) %pred FVC of 65 (51-78) were enrolled. Stabilisation/improvement in FVC was seen in 16 (94.1%) and 13 (76.5%) subjects in the pirfenidone and placebo groups, respectively (p = 0.33). The median (range) absolute change in %pred FVC was - 0.55 (- 9 to 7%) and 1.0 (- 42 to 11.5%) in the treatment and control groups, respectively (p = 0.51). The changes in 6MWD, dyspnoea scores, MRSS, and levels of TNF-α and TGF-β were not significantly different between groups. Common adverse events were gastrointestinal disturbances and skin rash. We failed to find a significant beneficial effect of pirfenidone over placebo in improving/stabilising FVC, exercise capacity, symptoms, or skin disease. Study is underpowered to provide conclusive evidence. Larger studies with longer follow-up periods are required.
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http://dx.doi.org/10.1007/s00296-020-04565-wDOI Listing
May 2020

Anti-Jo-1 Syndrome Often Misdiagnosed as Rheumatoid Arthritis (for Many Years): A Single-Center Experience.

J Clin Rheumatol 2021 Jun;27(4):150-155

From the Clinical Immunology and Rheumatology Division, Department of Internal Medicine.

Background: Antisynthetase syndrome is characterized by a triad of myositis, arthritis, and interstitial lung disease. Anti-Jo-1 is the most common associated autoantibody. This study planned to look at the presentation of anti-Jo-1 antisynthetase syndrome in a single Indian center.

Methods And Materials: This was a medical records review single-center study that included patients with anti-Jo-1 antisynthetase syndrome over 10 years.

Results: This study included 27 patients with anti-Jo-1 antisynthetase syndrome, with mean age of 40 ± 9.2 years and female preponderance (female-to-male ratio, 4:1). At presentation, the characteristic triad was present in only 4 patients. A majority presented with the incomplete form, with 2 clinical features (of triad) in 11 and single feature (of triad) being present in 12 patients at initial presentation. Seven presented only with polyarthritis, out of which 6 had been earlier diagnosed as rheumatoid arthritis. Time gap from diagnosis of "rheumatoid arthritis" to antisynthetase syndrome ranged from 3 to 20 years. In patients who had only arthritis in the beginning, there was a significantly longer delay to diagnosis of antisynthetase syndrome, higher frequency of rheumatoid factor, and lower frequency of anti-Ro-52. Overall, outcome was good, with Eastern Cooperative Oncology Group class 1 or 2 in most except 2 patients.

Conclusions: Anti-Jo-1 antisynthetase syndrome commonly presented as incomplete (not a triad) and often only with arthritis. These patients are diagnosed and treated as rheumatoid arthritis for many years, before a diagnosis of antisynthetase syndrome is made. Being aware of this presentation may help in earlier diagnosis by actively searching for subtle clues.
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http://dx.doi.org/10.1097/RHU.0000000000001234DOI Listing
June 2021

Effect of mycophenolate mofetil (MMF) on systemic sclerosis-related interstitial lung disease with mildly impaired lung function: a double-blind, placebo-controlled, randomized trial.

Rheumatol Int 2020 Feb 7;40(2):207-216. Epub 2019 Dec 7.

Department of Internal Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India.

The efficacy and safety of mycophenolate mofetil (MMF) has been studied in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD) with moderate-severe impairment. There is no study on its use in patients with mildly impaired lung function. The objective of this study is to determine the efficacy and safety of MMF for treating mild SSc-ILD (forced vital capacity (FVC) ≥ 70% predicted). This was a double-blind, randomized, placebo-controlled pilot trial. The subjects with SSc-ILD with FVC ≥ 70% were randomized to receive either MMF (2 g/day) or placebo for 6 months. FVC, diffusing capacity of lungs for carbon monoxide (DLCO), modified Rodnan skin score (mRSS), Short Form-36 (SF36v2), Mahler's Dyspnoea Index (MDI), and 6-min walk distance (6MWD) were recorded at baseline and at 6 months. Forty-one subjects were included in the study (MMF: 20, placebo: 21). FVC decreased by a median of 2.7% (range - 21 to 9) in MMF arm and increased by 1% (range - 6 to 10) in placebo arm (p = 0.131). SF36v2 scores improved in both the groups. Median change in MDI (3 vs 3), DLCO (1% vs 1.5%), and 6MWD (0 m vs 0 m) was similar between the study groups. MMF was effective in improving mRSS (- 5 vs - 1, p = 0.045) compared to placebo. Adverse events occurred with similar frequency in both the study groups. In this pilot study, MMF did not result in significant improvement in lung function in SSc-ILD with minimally impaired lung function, but was effective in reducing the skin tightness. Larger studies are needed to confirm these findings. This study was registered at ClinicalTrials.gov (NCT02896205).
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http://dx.doi.org/10.1007/s00296-019-04481-8DOI Listing
February 2020

Calcinosis Cutis at an Unusual Location.

J Clin Rheumatol 2020 Sep;26(6):e200

From the Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1097/RHU.0000000000001069DOI Listing
September 2020

Keloidal Morphea: Clinical Picture.

J Clin Rheumatol 2020 Sep;26(6):e178-e179

From the Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1097/RHU.0000000000001053DOI Listing
September 2020

Differentiating disease activity from damage in systemic sclerosis: it's still early days!

Ann Rheum Dis 2020 08 22;79(8):e98. Epub 2019 May 22.

Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, Indiaa

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http://dx.doi.org/10.1136/annrheumdis-2019-215588DOI Listing
August 2020

Chikungunya: A rheumatologist's perspective.

Int J Rheum Dis 2018 Mar 12;21(3):584-601. Epub 2018 Feb 12.

Unit of Clinical Immunology and Rheumatology, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Chikungunya (CHIK), a viral infection, is transmitted by Aedes mosquitoes. It is characterized by a phase of acute infection, which is sometimes followed by chronic rheumatisim in the form of arthralgia or myalgia that can last for months and even years. Several studies have been conducted to understand the mechanisms underlying inflammation associated with CHIK infection, persistence of viruses in monocytes-macrophages, and their relationship to the chronic symptoms. Chronic arthritis is one of the serious complications of CHIK infection, which is characterized by swelling and acute pain that poorly responds to treatment with analgesics. Such debilitating chronic joint pain mimics that of rheumatic arthritis and significantly compromises the quality of life. Diagnosis is primarily based on the initial viral detection using molecular methods or the use of virus culture, and on the basis of an immune response in the later stages. In the absence of published guidelines, physicians are often limited to prescribing analgesics and steroids for symptomatic care, as there is no accurate approach for the treatment and management of pain. This review aims to focus on the need for appropriate guidelines that will aid in developing suitable pharmacologic treatment to manage pain associated with post-CHIK chronic inflammatory rheumatism.
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http://dx.doi.org/10.1111/1756-185X.13273DOI Listing
March 2018

Use of Biologics and Biosimilars in Rheumatology.

J Assoc Physicians India 2017 May;65(5 Suppl):9-14

PGIMER, Chandigarh.

Prior to the availability of biologics, synthetic DMARDs (Disease modifying anti-rheumatic drugs) were the mainstay of the treatment in rheumatology. With the introduction of biologics, the scenario is changing to become more promising. These drugs have innovative mechanism of action, based on the targeted inhibition of specific molecular or cellular targets directly involved in disease pathogenesis. The biosimilars are highly similar copies of originator biologics approved through pre-defined, stringent regulatory processes after rigorous physicochemical, non-clinical, and clinical evaluations. Low cost and resulting wider patient access as compared to innovators goes in favor of biosimilars. Regulatory guidelines for biosimilar development and approval are rigorous and undergoing constant refinement. Approval of several biosimilars in across the world in last few years bears testimony to the increased regulatory acceptance of these agents. This article addresses development of biosimilars, regulatory process, benefits and concerns about their usage in rheumatologic practice.
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May 2017

A randomized controlled trial to study the efficacy of sulfasalazine for axial disease in ankylosing spondylitis.

Int J Rheum Dis 2018 Jan 24;21(1):308-314. Epub 2017 Jul 24.

Departments of Internal Medicine, Unit of Clinical Immunology and Rheumatology, Post-Graduate Institute of Medical Research (PGIMER), Chandigarh, India.

Aim: To evaluate efficacy of sulfasalazine for axial ankylosing spondylosis.

Methods: 67 patients fulfilling the inclusion criteria were included and randomized into treatment and placebo group.

Results: Mean age in treatment group was 31 years (range: 17-60); placebo group was 30 years (18-46). Mean disease duration treatment group 8.4 years (range: 3-25) and placebo group was 8.3 years (3-19). Clinically significant improvement in ASDAS (ΔASDAS > 1.1) seen in 15.1% of placebo and 67.7% in treatment group (P = 0.001). The mean ± SD of ΔASDAS in treatment group was 1.33 ± 0.38 (range: 0.9-2.3) where as in placebo group it was 0.748 ± 0.23 (0.4-1.3) with significant difference (P = 0.00). The mean ± SD of ΔBASDAI of treatment group was 3.29 ± 0.97 (range: 1.5-5.5) placebo group was 1.47 ± 0.99(0.5-4.5) with P = 0.00. The mean value of ΔBASMI of drug group 3.29 ± 0.97(range: 1.8-5) and of placebo group was 1.47 ± 0.99 (0.6-3.7) with (P = 0.00). Clinical improvenent in (ΔASDAS > 1.1) was observed in patients of both the groups with disease duration ≤ 4 years. However it was significantly higher in treatment group (P = 0.04). Highly significant improvement in (ΔASDAS > 2) was observed in two of five patients in treatment group with disease duration ≤ 4 years.

Conclusion: Sulfasalazine is effective in axial AS esp. in younger patients (< 25 years), disease duration < 4 years at the time of initiation of treatment and high disease activity (BASDAI > 7, CRP > 50 mg/L). This signifies early diagnosis and treatment is very important in management and prevention of disease progression.
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http://dx.doi.org/10.1111/1756-185X.13124DOI Listing
January 2018

Gastrointestinal Dysmotility and Infections in Systemic Sclerosis- An Indian Scenario.

Curr Rheumatol Rev 2018 ;14(2):172-176

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Introduction: Systemic Sclerosis is known to involve the gastrointestinal system and can lead to multitude of problems predominantly affecting the GI motility.

Methods: It was a prospective, observational, single centre study of fifty consecutive patients with SSc who presented to rheumatology clinic. Gut score was assessed using UCLA SCTC GIT 2.0 questionnaire. 35 patients underwent esophago- gastro duodenoscopy(UGIE), 31 underwent esophageal manometry, 37 underwent lactulose breath test to assess orocaecal transit time (OCTT) and glucose breath test for detecting small intestinal bacterial overgrowth (SIBO) and 36 underwent gastric emptying scintigraphy to measure gastric emptying time.

Results: GI involvement was seen in 98% of patients, with most common symptom being regurgitation (78%). Mean T score of the GUT score was 0.60±0.27. In UGIE, esophagitis was seen in 30, of which 3 had candidiasis and 1 had HSV esophagitis. Hiatus hernia was noted in 10 patients. Mean lower esophageal sphincter pressure was 16.1± 12.7 mmHg with hypotensive sphincture in twelve patients. Esophageal peristaltic abnormalities were observed in 28(90%) patients. Gastric emptying was delayed in10/36 patients. OCTT was prolonged in 23/ 37 patients whereas SIBO was noted in 7/37.

Conclusion: GI involvement is common in SSc with esophagus being most commonly affected. Motility abnormalities make them prone for super added infections especially infectious esophagitis and SIBO and should be investigated for early detection and treatment.
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http://dx.doi.org/10.2174/1573397113666170425145405DOI Listing
October 2018

The role of danger-associated molecular patterns (DAMPs) in trauma and infections.

J Thorac Dis 2016 Jul;8(7):1406-9

Department of Internal Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

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http://dx.doi.org/10.21037/jtd.2016.05.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958879PMC
July 2016

Can thyroid volume predict thyroid dysfunction in patients with systemic sclerosis? A prospective cross-sectional study from a tertiary care center in North West India.

Clin Rheumatol 2016 Mar 9;35(3):765-9. Epub 2016 Feb 9.

Department of Endocrinology, PGIMER, Chandigarh, India.

Previous studies have documented an association between thyroid dysfunction, predominant hypothyroidism, and antibody positivity in patients with systemic sclerosis (SSc). There are no studies reporting the relationship between thyroid volume and thyroid functions in patients with SSc. This study was conducted to correlate thyroid dysfunction with thyroid volume as measured on ultrasound and antibody positivity. Complete thyroid workup was done in 106 patients of SSc which included thyroid function test, antithyroid peroxidase (TPO) antibody, antithyroid-stimulating hormone receptor (TSHR) antibody, antithyroglobulin antibody, and thyroid ultrasound to assess thyroid volume, echogenicity and blood flow, and fine needle aspiration cytology of suspicious thyroid lesions. Prevalence of subclinical hypothyroidism was 8.5 %, overt hypothyroidism 1.9 %, subclinical hyperthyroidism 2.8 %, and overt hyperthyroidism in 0.9 % of the patients. Antithyroid peroxidase antibody was positive in 16 %, anti-TSH receptor antibody in 5.7 %, and antithyroglobulin antibody in none of the patients. Thyroid volume was in the range of atrophy (<4.5 ml) in 57.5 % patients, echogenicity altered in 15.1 %, and blood flow increased in 15.1 %. Thyroid volume correlated strongly with the pulmonary function test (FEV1). Routine thyroid ultrasound and thyroid function tests may be included in the workup of patients with SSc for the early detection of hypothyroidism since a small but significant percentage of patients developed thyroid dysfunction. Antithyroid antibodies may not correlate with the thyroid functions and hence should not be recommended.
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http://dx.doi.org/10.1007/s10067-016-3209-xDOI Listing
March 2016
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