Tag Archives: cyclosporine

Treatments for “Bad” Inflammatory Bowel Disease (Part 3)

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D Tarabar et al. Inflamm Bowel Dis 2022; 28: 1549-1554. A Prospective Trial with Long Term Follow-up of Patients With Severe, Steroid-Resistant Ulcerative Colitis Who Received Induction Therapy With Cyclosporine and Were Maintained With Vedolizumab

As noted previously, in my view, “bad” inflammatory bowel disease (IBD) occurs when treatments are not working; though, many would argue that any IBD is bad IBD. Today’s post concludes several reviewed articles that focus on the problem of IBD that is not responding well to treatment.

Methods: Seventeen steroid-resistant adult UC patients were treated with cyclosporine in combination with vedolizumab, with a follow up of 52 weeks. Only 2 patients in this chort had failed infliximab therapy. The authors administered IV cyclosporine at a dose of “2 to 4 mg/kg/d IV for 7 days, titrated to a goal trough level of 300 to 400 ng/mL.” In those with a response, patients were started on oral therapy along with IV vedolizumab. During oral therapy (for 8 weeks), goal trough levels were 150 to 250 ng/mL (measured weekly).

Key findings:

  • Fifteen (88%) of 17 patients initially responded to cyclosporine and were started on vedolizumab
  • At week 10, 11 (73%) of 15 patients had achieved endoscopic remission with a Mayo score of ≤1. 
  • At week 26, 14 (93%) of 15 of the patients were in clinical remission and 11 (73%) were in endoscopic remission.
  • At week 52 of follow-up, 10 (71%) of 14 of these patients continued to be in endoscopic remission and 11 (79%) of 14 were in clinical remission.
  • Colectomy-free survival rate was 82% (n = 14 of 17) at 1 year and mean C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin levels were 3.2 mg/L, 16.1 mm/h, and 168.3 µg/g, respectively

My take: Cyclosporine is a fast-acting medication and thus appropriate as a salvage therapy in those with severe disease. Concerns for adverse effects have led most pediatric GIs to favor infliximab for refractory severe UC. However, in selected patients, it could be a useful “bridge” to slower-acting long-term treatments. It is possible (likely) that insurance issues would be less with cyclosporine than tofacitinib as a bridge therapy.

**An alternative agent to cyclosporine is tacrolimus. Hamel B, Wu M, Hamel EO, Bass DM, Park KT. Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis. BMJ Open Gastroenterol. 2018;5(1):e000195 (“Positioning Biologic Therapies in the Management of Pediatric Inflammatory Bowel Disease” & 14% of U.S. Infected with COVID-19)

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Island Ford National Recreational Area, Sandy Springs GA

Slim Pickings: Data for 2nd-Line Autoimmune Hepatitis Pediatric Therapy

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A recent study (AN Zizzo et al. JPGN 2017; 65: 6-15) performed a systematic review and meta-analysis of pediatric autoimmune hepatitis (AIH) studies.

The most remarkable finding was that there were only 76 patients from 15 qualifying studies.

Other findings:

  • Response to mycophenolate mofetil (MMF) with 34 patients was 36% (according to abstract) at 6 months  (discrepancy in article –results state 38% response)
  • Response to cyclosporine with 15 patients was 83% (discrepancy in article –results state 86% response)
  • Response to tacrolimus with 4 patients was 50%
  • Adverse effects were very common, particularly with cyclosporine (64% noted at least 1 adverse effect)

The article has an associated editorial (N Kerkar, pg 2-3).  “The adverse event profile of cyclosporine with gingival hyperplasia, hypertrichosis, nephrotoxicity, and neurotoxicity made it challenging for long-term use in children.”  Besides the small number of patients, “the studies that were included were largely “observational”‘ which limits their findings as well.  The study authors recommend MMF as the preferred option for 2nd-line therapy.

My take: Fortunately, most patients with autoimmune hepatitis respond to first line therapy with azathioprine/steroids.  It is unclear what is the optimal 2nd-line treatment for refractory patients.

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Egret, Shem Creek

Hemophagocytic Lymphohistioctosis: Advances

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A recent medical progress report provides a concise update on hemophagocytic lymphohistiocytosis (HLH) (J Pediatr 2013; 163: 1253-59).

  • Table 1 summarizes the subtypes of HLH.
  • Atypical presentations include colitis and hypogammaglobulinemia.
  • Table 2 provides the diagnostic criteria.
  • The treatment approach is outlined as well.  In the short-term, with primary HLH, the goal is controlling the hyperinflammatory state (often with dexamethasone and etoposide).  The long-term goal aims to definitively correct the underlying genetic defect by allogeneic hematopoietic stem cell transplantation (HCT)

Other points:

  • A genetic diagnosis of familial HLH can be made in 40-80% of HLH cases with the identification of PRF1, UNC13D, STX11, and STXBP2 genes.
  • UNC13D are the predominant defects identified in Caucasians in U.S.
  • PRF1 is most common in African-American patients.
  • Ferritin remains an excellent screening tool.  A level >500 mcg/L is suggestive (but not specific) for HLH; a level >10,000 has much greater specificity (96%) along with fairly high sensitivity (90%).
  • HLH is commonly referred to as macrophage activation syndrome (MAS) in the setting of a rheumatologic illness.
  • There is no broad consensus on management of secondary HLH.  In MAS, therapy often includes pulsed steroids and/or cyclosporine.

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