Systemic sclerosis associated interstitial lung disease: a conceptual framework for subclinical, clinical and progressive disease.

OBJECTIVES: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). METHODS: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification. RESULTS: Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration. CONCLUSIONS: Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT.

Co prescription of anti-acid therapy reduces the bioavailability of mycophenolate mofetil in systemic sclerosis patients: A crossover trial.

OBJECTIVE: Mycophenolate mofetil (MMF) is an effective treatment option for interstitial lung disease (ILD) in systemic sclerosis (SSc). Many patients require co-administration of proton pump inhibitors (PPI) or H2 receptor blockers (HRB) because of various gastrointestinal (GI) manifestations in SSc. Co-treatment with PPI or HRB have shown to reduce serum drug levels in post-transplant patients. We wanted to see if there is a similar phenomenon for Mycophenolate in SSc. METHODS: Twenty SSc patients, who were on a stable dose of MMF (1.5-3 g) underwent a sequential cross over study with MMF alone in the first month, followed by co-treatment with Ranitidine and then Esomeprazole in the second and third month respectively. Estimation of 12-hour area under curve (AUC) of Mycophenolic Acid (MPA) levels and total GI score were calculated at the end of each month and compared between the treatment arms. [Trial registration: CTRI/2020/06/025,939] RESULTS: Co-administration of esomeprazole was associated with 32.7% (mean difference = 22.28 µg h ml-1) reduction in mean AUC MPA, whereas ranitidine caused a reduction of 21.97% (mean difference = 14.93 µg h ml-1) in MPA AUC when compared to MMF without anti-acid therapies. The addition of ranitidine or esomeprazole resulted in significant reduction in the total GI score. CONCLUSION: Co-administration of PPI or HRB can significantly reduce the bioavailability of MMF in patients with SSc. To avoid therapeutic failure of MMF drug level monitoring is essential when these agents are co-prescribed with MMF.

Efficacy of tadalafil in secondary Raynaud's phenomenon resistant to vasodilator therapy: a double-blind randomized cross-over trial.

OBJECTIVE: To evaluate the efficacy of tadalafil as add-on therapy in secondary RP resistant to vasodilators. METHODS: Patients with scleroderma and MCTD having four or more RP attacks per week despite being on vasodilators were randomized to receive either placebo or tadalafil (20 mg) on alternate days as add-on therapy to their current vasodilators for 6 weeks. After a 7-day washout, patients were crossed over to the other arm. Primary endpoints were improvement in the daily frequency and duration of RP episodes and RP condition score (RCS). Secondary outcome measures were healing of existing and appearance of new digital ulcers (DUs) and improvement in scleroderma-specific HAQ (SHAQ), quality of life (QoL), flow-mediated dilatation (FMD), patient and physician global assessment. RESULTS: Twenty-four of 25 recruited patients completed the study. All the patients were receiving calcium channel blockers and in addition 18 were receiving other vasodilators. During tadalafil therapy significant improvement in mean daily frequency, mean daily duration of RP and mean daily RCS were observed as compared with baseline and placebo. All the 24 digital lesions healed during tadalafil therapy as compared with 3/13 during the placebo treatment (P<0.0001). One new DU was reported during tadalafil therapy vs 13 during placebo therapy (P=0.0005). QoL, SHAQ, FMD, patient and physician global assessment significantly improved while on tadalafil. No serious adverse event was observed. CONCLUSION: Tadalafil as add-on therapy improves symptoms of RP, heals and prevents new DUs and improves QoL in patients with resistant secondary RP. TRIAL REGISTRATION: Clinicaltrials.gov, http://clinicaltrials.gov/, identifier: NCT00626665.

Efficacy of rituximab in resistant palindromic rheumatism: first report in literature.

BACKGROUND: Rituximab (RTX) provides significant clinical benefits in active rheumatoid arthritis (RA) patients with inadequate response to DMARDs and anti-TNF. There is no data regarding efficacy of RTX in seropositive Palindromic Rheumatism (PR), a forerunner of RA. AIM: To determine the efficacy and safety of RTX treatment in active PR patients exhibiting inadequate response to conventional synthetic DMARDs (csDMARDs). METHODS: The retrospective study, over a period of 3 years, included seropositive (RF ± antiCCP) PR patients with inadequate control of PR (> 4 attacks per months) despite combination csDMARDs and were treated with RTX. All the patients were treated with an initial dose of 500 mg RTX and later with a second infusion after 2 weeks' period in those who did not achieve adequate/ complete disease control. Patients were continued on csDMARDS and retreated with RTX on relapse of symptoms. RESULTS: Thirty-three seropositive PR patients with a mean age of 48.15 ± 14.2 years, mean disease duration of 68.4 ± 68.2 months, mean follow up period of 24.3 ± 10.8 months, were treated with RTX. 88% patients were on combination DMARDS and 79% patients were females. All patient achieved rapid and complete control of palindromic attacks with RTX. Fifteen patients had a relapse after a mean duration of 10.4 ± 5.5 months and needed repeat RTX infusions following which remission was achieved. None of the patients progressed to RA till the end of the follow-up. No serious adverse effects were recorded. CONCLUSION: RTX treatment could be effective in achieving disease control in active palindromic rheumatism not responding to csDMARDs. KEY POINTS: • PR is thought to be a forerunner of RA and rituximab (RTX) has been found to be effective in RA. • Our study supports the hypothesis that B cells play an important role in the pathophysiology of PR and that the combination (RTX+ conventional drugs) can prevent the disease evolution into RA. • This 3-year retrospective study showed that rituximab was found to be effective in those who responded poorly to conventional drugs and remission was achieved in all patients. • Although it is a rare disease, we see palindromic rheumatism patients in India more often. As the symptoms are very debilitating in these patients, in those patients, not controlled on conventional drugs, rituximab offers newer promise in controlling the attacks and prevents further progression to RA.

Cyclophosphamide versus mycophenolate mofetil in scleroderma interstitial lung disease (SSc-ILD) as induction therapy: a single-centre, retrospective analysis.

BACKGROUND: Scleroderma is a systemic autoimmune disease characterized mainly by skin manifestations and involvement of various visceral organs, especially the lungs. Lung involvement is the leading cause of mortality in patients with scleroderma. There are data to suggest that cyclophosphamide (CYC) and mycophenolate mofetil (MMF) are effective in the management of scleroderma interstitial lung disease (SSc-ILD) but no head to head comparative data are available to date. METHODS: For the last 3 years, patients with SSc-ILD have been treated at our centre by protocol-based administration of intravenous CYC and MMF. Results of lung function tests (spirometry) were recorded at baseline, 3 months and 6 months in every patient. The clinical records of patients with systemic sclerosis and significant ILD, who were not previously exposed to any immunosuppressant and were treated with MMF OR CYC, were reviewed. The efficacy of treatment was assessed by the change in forced vital capacity on spirometry. RESULTS: Of the total 57 patients included in the analysis, 34 were treated with MMF and 23 were treated with CYC. Mean duration of illness was 4.19 ± 2.82 years in the MMF and 6.04 ± 5.96 years in the CYC group. After 6 months of therapy, FVC increased by 10.84 ± 13.81 % in the CYC group and by 6.07 ± 11.92 % in the MMF group. This improvement from baseline was statistically significant in both groups (P < 0.01). The improvement was comparable with no statistically significant differences between groups (P = 0.373). There were no major adverse events reported in either arm. CONCLUSION: Both MMF and CYC were equally effective in stabilizing lung function in patients with scleroderma and ILD.