Adalimumab sustains clinical remission and overall clinical benefit after 2 years of therapy for Crohn’s disease

Aliment Pharmacol Ther 31 , 1296–1309

Summary

Background In the randomized, double‐blind, placebo‐controlled CHARM trial, adalimumab was more effective than placebo in maintaining clinical remission for patients with moderate‐to‐severe Crohn’s disease (CD) through 56 weeks. Aim To substantiate the long‐term safety and clinical benefits of adalimumab through 2 years of therapy in CHARM and its open‐label extension (ADHERE). Methods Patients entering ADHERE on blinded therapy received adalimumab 40 mg every other week (eow). Patients who had already moved to open‐label adalimumab eow or weekly in CHARM continued their regimens. Data were analysed by originally randomized treatment group at CHARM baseline (adalimumab 40 mg eow, adalimumab 40 mg weekly, or placebo), regardless of whether patients entered ADHERE or received open‐label adalimumab (eow or weekly). Results After up to 2 years of therapy, 37.6%, 41.9% and 49.8% of patients originally randomized to placebo, adalimumab eow and adalimumab weekly, respectively, were in clinical remission. All groups experienced sustained improvements on the Inflammatory Bowel Disease Questionnaire. Decreasing hazard rates for both all‐cause and CD‐related hospitalizations were observed over time. Over a 2‐year period, the rates of serious adverse events and malignancies (33.3 and 1.1 events/100‐patient‐years respectively) were similar to those observed during the overall adalimumab CD clinical development programme. Conclusions Adalimumab demonstrated sustained maintenance of clinical remission, improvements in quality of life and reductions in hospitalization during long‐term treatment for CD, with no new safety concerns identified.     

Leflunomide for the treatment of rheumatoid arthritis in clinical practice: incidence and severity of hepatotoxicity.

OBJECTIVE: Leflunomide is a novel disease modifying antirheumatic drug (DMARD). Because of reports on possible hepatotoxicity and adaptations in the recommendations for monitoring liver function during leflunomide treatment, we conducted a study to evaluate the incidence and severity of hepatotoxicity. METHODS: We included consecutive rheumatoid arthritis patients starting treatment with leflunomide in the region of Friesland (The Netherlands) between January 2000 and January 2002. During follow-up patient characteristics, disease characteristics, and clinical and laboratory data on liver functions were registered. Severity of hepatotoxicity was categorised using the National Cancer Institute Common Toxicity Criteria, as moderate (grade 2), severe (grade 3) or life threatening (grade 4). RESULTS: One hundred and one patients were followed for a median period of 10 months (range 0.5-12). Grade 2 or 3 elevations in any liver function blood test were recorded in a total of nine patients (8.9%). No grade 4 elevations were recorded. Four patients (4%) showed grade 2-3 aminotransferase elevations. Due to grade 2 hepatotoxicity one patient (1%) was withdrawn from leflunomide treatment, and one patient continued leflunomide at a reduced dose. In eight of nine patients with grade 2-3 liver function blood tests, these elevated liver function tests occurred within 6 months after starting leflunomide. None of the patients with grade 2 or 3 toxicity had a history of hepatic disease, eight patients concomitantly used potential hepatotoxic co-medication. Eight (8%) patients used leflunomide in combination with methotrexate, and one of these patients developed hepatotoxicity. No clinical signs of serious hepatotoxicity were recorded during follow-up. DISCUSSION: In 8.9% of the patients, grade 2 or 3 hepatotoxicity was recorded within the first year after the start of leflunomide therapy based on liver enzyme determinations. In the majority of the patients liver enzyme elevations occurred within the first 6 months of therapy and resolved during continued follow-up. None of the patients showed clinical signs of hepatotoxicity. CONCLUSION: Under continued monitoring of liver functions hepatotoxicity during leflunomide use does not seem to be a major problem in our population.     

Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation

Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.     

Neonatal lupus: clinical features and management

Neonatal lupus is an uncommon autoimmune disease manifested primarily by cutaneous lupus lesions and/or congenital heart block. Maternal autoantibodies of the Ro/La family are present in virtually every case, although only approximately 1% of women who have these autoantibodies will have a baby with neonatal lupus. The cutaneous lesions of neonatal lupus may be present at birth, but more often develop within the first few weeks of life. Lesions are most common on the face and scalp, often in a distinctive periorbital distribution. Lesions tend to resolve in a few weeks or months without scarring. The most common cardiac manifestation of neonatal lupus is complete heart block. Heart block typically begins in utero during the second or third trimester. In some cases, heart block begins as first- or second-degree block and then progresses to third-degree block. Complete heart block, once established, appears to be irreversible. In some cases, cardiomyopathy occurs together with complete heart block. Most cases have been noted at birth, but delayed dilated cardiomyopathy has been reported. There have been a few cases of endocardial fibroelastosis occurring in the absence of congenital heart block. Hepatobiliary disease occurs in about 10% of cases. Three types of hepatobiliary disease have been observed: liver failure occurring at birth or in utero, transient conjugated hyperbilirubinemia occurring in infants, or transient transaminase elevations occurring in infants. Hematologic disease, consisting of thrombocytopenia, neutropenia, or anemia, occurs in about 10% of cases. It is common for children with neonatal lupus not to have the full expression of disease, but rather to have only one or two organ systems involved. The diagnosis rests largely on the finding of compatible clinical manifestations plus maternal autoantibodies to Ro and/or La, or, in a few cases, to U1 ribonuclear protein. Although the pathogenesis has not been conclusively established, accumulating evidence, including evidence from animal models, implicates autoantibodies in the pathogenesis of the disease. Therapeutic interventions include attempts at prevention, early intervention, and treatment of well established disease, mainly through the use of systemic corticosteroids. Optimal therapy has yet to be determined. The long-term prognosis for children who have had neonatal lupus is still under investigation, but some children who had neonatal lupus have developed other autoimmune diseases later in childhood. About half of the mothers are asymptomatic at the time of presentation of the child, but some of these women eventually develop symptoms of autoimmune disease.     

Safety and Efficacy of Biologic Agents for the Management of Inflammatory Bowel Disease After Liver Transplantation

Primary sclerosing cholangitis (PSC) frequently progresses to end‐stage liver disease and cirrhosis, requiring liver transplantation. Approximately 70% of patients with PSC have concomitant inflammatory bowel disease (IBD) during their clinical course. After liver transplantation for PSC, corticosteroids and other high‐intensity immunosuppressants are initiated to keep IBD in remission. Patients with IBD that is refractory to these agents may need to be managed with biologic therapies. Biologic agents, however, may further increase the risks for malignancy and infection due to their immunosuppressive effects. Thus, to gain a better understanding of the risks and benefits of these agents in this high‐risk patient population, we performed a literature search of the PubMed database (2002–2017) to identify studies assessing the efficacy and safety of various biologic agents for the management of IBD in liver transplant recipients. No randomized controlled studies or retrospective comparative studies were identified; however, 15 case reports and case series were identified that met our inclusion criteria. From these case reports, we identified 67 patients who developed de novo or recurrent IBD after liver transplantation and received anti–tumor necrosis factor‐α or anti‐integrin therapy. Of the 13 published cases reporting clinical response or remission of IBD activity in liver transplant recipients (59 patients), clinical response or remission of IBD was reported in 38 (64.4%) of those patients. Adverse complications reported included cholangitis, oral candidiasis, Clostridium difficile colitis, bacterial pneumonia, cryptosporidiosis, Epstein–Barr virus–positive posttransplantation lymphoproliferative disease, and hepatotoxicity. Given the limited literature (case reports and case series) highlighted in this review, biologic agents such as tumor necrosis factor‐α inhibitors and integrin inhibitors commonly used for moderate to severe IBD may be appropriate after liver transplantation; however, consideration of risk versus benefit should always occur in a patient‐specific manner.     

Crohn's disease: a review of current treatment with a focus on biologics

Crohn's disease is a debilitating and expensive disease that is growing in incidence in both developing and developed countries. While conventional therapies, such as corticosteroids and immunosuppressants, continue to play a vital role in treating this condition, it is evident that many affected individuals do not respond to therapy or develop intolerable adverse effects. The addition of modern biological therapies to the Crohn's disease armamentarium is providing a change in expectations for disease outcome. Infliximab and adalimumab are currently the only biological agents approved for induction and maintenance treatment in adults (infliximab and adalimumab) and children (infliximab) with Crohn's disease. Furthermore, infliximab has a beneficial effect on perianal fistulas. Other tumour necrosis factor (TNF)-alpha inhibitors, such as certolizumab pegol, also demonstrate promising results in adults with moderate to severe active disease. In addition, adalimumab and certolizumab pegol have shown clinical efficacy in patients who are intolerant to or lose response to infliximab, suggesting that switching between agents may allow response to be maintained over time. The primary safety concerns with TNFalpha inhibitors include increased risk of serious infection (including reactivation of tuberculosis), malignancy (particularly lymphoma) and demyelinating disease. Other agents in development include recombinant human anti-inflammatory cytokines, agents that target pro-inflammatory cytokines and granulocyte-macrophage colony-stimulating factors. Further prospective studies will provide interesting insight into different mechanisms by which factors involved in the pathophysiology of Crohn's disease can be modulated.     

Tumour necrosis factor antagonists and inflammatory bowel diseases: a national practice survey

Background  Although the use of tumour necrosis factor (TNF) antagonists is increasingly codified, several unresolved issues remain.
Aim  To conduct a French national survey on TNF antagonists use in inflammatory bowel disease (IBD).
Methods  A postal questionnaire was sent to all French gastroenterologists among whom 450 prescribe TNF antagonists for IBD. Only anti-TNF prescribers were invited to respond.
Results  A total of 333 questionnaires could be analysed, which represented a rate of survey completeness of 74%. Scheduled maintenance infliximab treatment was prescribed by 92% of gastroenterologists. In Crohn's disease in remission after 1 year of TNF antagonists, 77.4% of physicians continued treatment. In luminal Crohn's disease, 97% of hospital practitioners introduced infliximab as first-line anti-TNF therapy vs. 78% of physicians with nonhospital activity ( P  = 0.002); only 22.5% of gastroenterologists opted for adalimumab as first-line therapy. In Crohn's disease in remission after 6 months of azathioprine in combination with infliximab, 63.8% of practitioners discontinued azathioprine. In case of pregnancy during anti-TNF treatment, 35.1% of physicians discontinued therapy at the time of conception and did not administer anti-TNF therapy during pregnancy.
Conclusions  The attitudes of French gastroenterologists generally reflect the recommendations regarding the use of anti-TNF and concomitant immunosuppressive therapy in IBD.     

The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn's disease who failed prior infliximab therapy

Aliment Pharmacol Ther 2010; 32: 1228–1239

Summary

Background Adalimumab induces and maintains remission in adults with Crohn’s disease. Aim To evaluate safety, fistula healing, quality of life and work productivity in adalimumab‐treated patients who failed infliximab, including primary nonresponders. Methods After a ≥8‐week infliximab washout, patients with moderate‐to‐severe Crohn’s disease received open‐label adalimumab as induction (160/80 mg at weeks 0/2) and maintenance (40 mg every other week) therapies. At/after 8 weeks, patients with flare/nonresponse could receive weekly therapy. Minimum study duration was 8 weeks, continuing until the commercial availability of adalimumab for Crohn’s disease. Results Of 673 patients enrolled, 17% were infliximab primary nonresponders and 83% were initial responders. Three percent of patients had serious infections (mainly abscesses). Complete fistula healing was achieved by 34/88 (39%) patients with baseline fistulas. Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients, as well as the subgroup of primary nonresponders. Conclusions Blinded clinical trials have shown adalimumab to be both an effective first‐line therapy for anti‐TNF‐naïve patients and an important treatment option for infliximab‐refractory or ‐intolerant patients. This trial presents open‐label experience to support further the safety and effectiveness of adalimumab in patients who failed infliximab therapy, including primary nonresponders (NCT00338650).     

Etanercept therapy in patients with psoriasis and concomitant HCV infection

Treatment of patients with psoriasis and/or psoriatic arthritis and concomitant hepatitis C infection remains difficult. Except for cyclosporine, other drugs have proved unacceptable because of hepatotoxicity in patients with HCV. With the advent of anti-TNF-alpha drugs, including etanercept, new therapeutic options have become available. Our study population was five patients with psoriasis and/or psoriatic arthritis and concomitant chronic HCV infection undergoing etanercept therapy. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and viral load were used as markers for liver damage and disease progression, respectively. The Psoriasis Area Severity Index (PASI) was used as a reference parameter for evaluating the therapeutic efficacy of etanercept therapy in improving the clinical skin picture. AST, ALT, viral load and PASI were monitored at 3-month intervals starting from the beginning of therapy up to two years after initiation of etanercept therapy. In four out of five patients, liver enzyme levels and viral load remained substantially unchanged during the course of therapy. In the one remaining patient, viral load and liver enzyme levels increased during etanercept therapy, and then decreased following the initiation of Peg-IFN/ribavirin in combination with anti-TNF-alpha therapy. PASI scores decreased in all five patients. Our data suggest that etanercept therapy is safe and provides an efficacious therapeutic alternative in patients with psoriasis and concomitant HCV infection.     

Alopecia areata during treatment of psoriasis with adalimumab and leflunomide: a case and review of the literature

The pathogenesis of alopecia areata (AA) is not clear, even though it is believed to be an autoimmune mechanism which involves T lymphocytes and cytokines such as tumor necrosis factor α. We report the case of a 43-year-old man with psoriasis and psoriatic arthritis who developed AA during his treatment with adalimumab and leflunomide. We perform a review of the literature associating AA with biological therapy and leflunomide. We cannot exclude that the use of these therapies and the development of AA could be coincidental. However, we consider that case reports like ours are essential for clinicians as early alerts if similar observations occur.     

Adalimumab in patients with Crohn's disease--safety and efficacy in an open-label single centre study

AIM: To evaluate the efficacy and safety of adalimumab, a human antitumour necrosis factor-alpha antibody, in induction and maintenance of remission in patients with Crohn's disease either refractory or intolerant to infliximab in a single centre cohort. METHODS: Sixteen Crohn's disease patients received 160 mg adalimumab subcutaneously in week 0, followed by 80 mg every other week. Clinical response was assessed based on Crohn's disease activity index and laboratory parameters (leukocyte count, C-reactive protein). In all patients genotyping for CARD15 variants and the +1059G/C polymorphism in the C-reactive protein gene was performed. RESULTS: In 10 of 16 patients (63%) treated with adalimumab, remission (CDAI score <150) was induced for at least 8 weeks independent of CARD15 or +1059G/C CRP status. In six of these 10 patients ongoing remission is observed now for more than 24 weeks. Adalimumab significantly decreased C-reactive protein serum levels and Crohn's disease activity index. There was one serious complication (fungal pneumonia). Six patients intermittently developed minor dermatological problems resolving after topical therapy. Otherwise, treatment was generally well tolerated. CONCLUSION: Adalimumab can induce and maintain remission in patients with moderate to severe Crohn's disease intolerant or refractory to infliximab. Further experience from larger cohorts is required to evaluate dose regimen and safety profiles in Crohn's disease therapy.     

Hepatic reactions during treatment of multiple sclerosis with interferon-beta-1a: incidence and clinical significance.

BACKGROUND: Hepatic dysfunction, manifested as liver enzyme elevations, occurs frequently in patients who are treated with interferon, however, data for patients with multiple sclerosis are limited.OBJECTIVE: To retrospectively assess the safety profile of interferon-beta-1a therapy with respect to liver function during clinical trials and postmarketing surveillance in the treatment of multiple sclerosis. PATIENTS AND METHODS: Adverse effects and laboratory abnormalities were analysed from six randomised, controlled clinical trials (five of which were placebo-controlled) that assessed the use of interferon-beta-1a in patients with multiple sclerosis. Treatment data were collected for 2819 patients for up to 12 months, of whom 1995 received interferon-beta-1a (337 [12%] received Avonex intramuscular therapy, and 1658 [59%] received Rebif subcutaneous therapy), and 824 (29%) received placebo. Data for 2 years were collated for 1178 patients (from two studies). Total weekly interferon doses were 22-132 microg. Postmarketing surveillance data were also analysed. RESULTS: In patients receiving interferon-beta-1a, there were significant elevations of alanine aminotransferase (ALT) levels, of all grades of severity, in up to 59% of patients at 6 months, up to 64% of patients at 12 months and up to 67% of patients at 24 months; ALT elevations were asymptomatic and dose related. More than 50% of elevations in liver enzymes occurred during the first 3 months of treatment, and more than 75% occurred during the first 6 months. Elevated enzyme levels resolved spontaneously or with dosage adjustment. Although the overall incidence of liver enzyme elevation was high during the early months of therapy, after 2 years, the proportion of patients with abnormal liver enzyme levels was 11% of those receiving Rebif 44 microg three times weekly compared with 6% of placebo-treated patients. Only 0.4% of patients discontinued interferon-beta-1a treatment because of hepatic adverse effects. Serious symptomatic interferon-related hepatic toxicity occurs, but is uncommon. Concomitant medication use was not associated with increased risk. CONCLUSION: Asymptomatic hepatic dysfunction is common in patients with multiple sclerosis who are treated with interferon-beta-1a, and is dose related. Adverse effects are mainly mild and transient, with little impact on adherence to therapy, although rare serious events can occur. Regular liver function monitoring during the first 6 months is recommended.     

Systematic review: the short-term and long-term efficacy of adalimumab following discontinuation of infliximab

Background  Therapy with adalimumab has been shown to be effective in Crohn's disease (CD) patients who have lost response or are intolerant to infliximab.
Aim  To determine the efficacy of adalimumab in CD patients who discontinued infliximab through a systematic review.
Methods  Electronic searches of EMBASE and MEDLINE databases up to May 1, 2009, as well as abstracts from the AGA (2006–2008), ACG (2006–2007), UEGW (2006–2008) and CDDW (2006–2009) identified randomized-controlled trials (RCT) or open-labelled cohorts (OLC) evaluating the short-term and/or long-term efficacy of adalimumab in infliximab failures. The response rates for short-term (clinical response and remission at 4 weeks) and long-term (remission at 6 and 12 months) efficacy were considered.
Results  A total of 1810 CD patients were identified among the 15 studies (2 RCT and 13 OLC). The majority of studies evaluated CD patients who either lost response or were intolerable to infliximab, although five OLCs permitted patients refractory to infliximab. Short-term clinical response ( n  = 9 articles) ranged from 41% to 83%. Long-term clinical remission at 12 months ( n  = 8 articles) ranged from 19% to 68%. The occurrence of severe adverse events ranged from 0% to 19% and four patients died.
Conclusions  Current RCT and OLC evidence suggest that adalimumab is an efficacious therapy for CD patients who discontinue infliximab.     

Systematic review: steroid withdrawal in anti‐TNF‐treated patients with inflammatory bowel disease

Aliment Pharmacol Ther 2010; 32: 313–323

Summary

Background The increasing awareness of increased risk for opportunistic infections when combining several immunosuppressant drugs led to new treatment goals for inflammatory bowel disease including limited use of steroids. Aim To conduct a systematic review to establish figures for steroid withdrawal in anti‐TNF treated inflammatory bowel disease‐patients. Methods Medline was searched using the search‐terms Ulcerative Colitis (UC) [Mesh], Crohn Disease (CD) [Mesh], IBD [Mesh], crohn, colitis, IBD and steroid sparing, all combined with infliximab and adalimumab. We selected English‐language publications that addressed the effect of anti‐TNF on steroid withdrawal. Studies had to assess patients with luminal CD or UC. Numbers of patients who were able to withdraw steroids were calculated. Results Six studies could be included; five reporting on infliximab and one on adalimumab. Studies were heterogeneously designed. Overall, in the adult population, up to 38% of the patients were able to withdraw corticosteroids during infliximab therapy. In the paediatric population, up to 75% of the patients were able to withdraw corticosteroids during infliximab therapy. Conclusions Although a consensus on the definition of steroid‐sparing is lacking, approximately two‐thirds of the inflammatory bowel disease‐patients are unable to withdraw corticosteroid treatment during anti‐TNF therapy.     

Adalimumab maintenance therapy for Crohn's disease with intolerance or lost response to infliximab: an open-label study

BACKGROUND: Adalimumab is effective in inducing remission in patients with active Crohn's disease who had secondary failure to infliximab therapy. AIM: To evaluate the efficacy and safety of adalimumab maintenance therapy in Crohn's disease patients who previously responded to infliximab and then lost response or became intolerant. METHODS: Twenty-four patients with Crohn's disease were enrolled in a 52-week open-label trial. The patients received a loading dose of adalimumab 80-mg at week 0, and then 40 mg every other week starting at week 2. The primary efficacy measure was clinical remission defined as Crohn's Disease Activity Index score < 150 at week 52. RESULTS: Five patients lost response to adalimumab. None of the patients experienced intolerance to adalimumab. Clinical remission rates were higher at weeks 4 (16/24, 67%) and 52 (14/24, 58%) compared with baseline (8/24, 35%) (P=0.043 at week 52). This was accompanied by a decrease in mean C-reactive protein concentration from 31.8 mg/mL at baseline to 9.7 mg/mL at week 52, and 3/4 (75%) patients achieved steroid-free remission. No serious toxicities occurred in the study. CONCLUSIONS: Adalimumab is well tolerated and appears to be effective in maintaining clinical remission in patients with Crohn's disease and lost response or intolerance to infliximab.     

Adalimumab sustains steroid-free remission after 3 years of therapy for Crohn's disease

Aliment Pharmacol Ther 2011; 34: 306–317

Summary

Background Treatments that achieve sustainable steroid‐free clinical remission in Crohn’s disease are needed; however, long‐term steroid‐sparing efficacy data are limited. Aim To evaluate steroid‐sparing efficacy and the impact of steroid discontinuation on adverse events during treatment of Crohn's disease with adalimumab in the phase III randomised, double‐blind 1‐year CHARM trial and for an additional 2 years in its open‐label extension ADHERE. Methods Steroid‐free remission and response and steroid‐sparing (≥50% steroid dose reduction) remission rates were evaluated over 3 years in patients who were taking corticosteroids at CHARM baseline. Results Of 778 patients randomised in CHARM (including those who did not achieve clinical response to open‐label induction therapy), 313 patients (40%) were on corticosteroids at baseline. In the 206 patients randomised to adalimumab, rates of steroid‐free remission at 1 year and 3 years were 26% and 23% respectively; corresponding rates were 29% and 25% for steroid‐sparing remission and 32% and 28% for steroid‐free response. Although the incidence of serious infections with adalimumab treatment during CHARM was higher in patients taking steroids at baseline than those who were not, the rates of overall adverse events, serious infections and opportunistic infections were lower in patients who were able to discontinue corticosteroids than those who remained on steroids. Conclusion Adalimumab therapy resulted in modest but clinically meaningful rates of steroid‐free remission, sustained over 3 years of treatment, in a heavily pretreated population of patients with Crohn's disease receiving steroids at the start of therapy ( http://www.clinicaltrials.gov number: NCT00077779).     

Factor XI deficiency diagnosed following use of adalimumab

Adalimumab is a drug used in the treatment of refractory psoriasis. We present a case of a 55-year-old male patient who developed petechiae and purpura after the ninth dose of adalimumab therapy. The results of laboratory investigations revealed factor XI (F.XI) deficiency. It should be recognized that F XI deficiency may develop in patients using long-term adalimumab, leading to increased risk of bleeding.KEY WORDS: Adalimumab, bleeding diathesis, bleeding, factor XI deficiency, psoriasis     

Mortality associated with concurrent strongyloidosis and cytomegalovirus infection in a patient on steroid therapy

Disseminated strongyloidosis has been recognized with increasing frequency, often in patients who are immunocompromised or have received steroid therapy. In addition, disease due to cytomegalovirus (CMV) is noted in immunodeficient hosts. We report on a 55-year-old Puerto Rican man who received steroid treatment for orpharyngeal pemphigus vulgaris and developed abdominal symptoms with alternating constipation and diarrhea. The clinical work-up did not reveal specific abnormalities, but the patient died of cardiopulmonary failure. At the postmortem examination, the patient had evidence of strongyloidosis and CMV disease. This report reviews both this case and the literature, and discusses the overlapping infections of strongyloidosis and CMV disease in this patient who had received steroid therapy.