Amy Karon

PD-1 checkpoint blockade via pembrolizumab is a potential option for classical Hodgkin’s lymphoma that progressed despite brentuximab vedotin therapy, based on a phase Ib, single-arm, open-label, industry-sponsored study of 31 patients.

After a median follow-up of 17 months, five (16%) patients achieved complete remission (90% confidence interval, 7%-31%), and 15 (48%) patients achieved partial remission (90% CI, 33%-64%), for an overall response rate of 65% (48%-79%). Furthermore, 70% of responses lasted at least 24 weeks, reported Philippe Armand, MD, of Dana-Farber Cancer Institute, Boston, and his associates.

“Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies,” they added. “Yet partial responses can be durable, suggesting that the achievement of complete response with checkpoint blockade is not necessary to derive significant clinical benefit.”

Pembrolizumab (Keytruda) is a humanized, highly selective IgG4 anti-PD-1 (programmed death-1) monoclonal antibody approved in the United States for patients with unresectable or metastatic melanoma or metastatic PDL-1 expressing non–small cell lung cancer. Tumor cells in classical Hodgkin lymphoma (HL) often overexpress PD-1 ligands, which “strongly suggests” that HL is PD-1 dependent, the researchers noted (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

The researchers analyzed data for one group of patients within a phase Ib study of pembrolizumab in hematologic malignancies (KEYNOTE-013; NCT01953692). These 31 adults (median age, 32 years; 58% male) all had heavily pretreated classical HL – more than half had received at least five prior lines of therapy, and all had progressed on or after brentuximab vedotin therapy. Most patients (71%) also had received autologous stem cell transplantation. All 31 patients in the study received intravenous pembrolizumab (10 mg/kg) every other week.

Rates of progression-free survival were 69% at 24 weeks and 46% at 52 weeks, the researchers said. “Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways,” they reported. Those findings indicate that PD-1 blockade activates T-cell and IFN-gamma signaling pathways, which provides “a compelling rationale for the further development of PD-1 blockade in HL,” they concluded.

The most common treatment-related adverse effects were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Five patients (16%) developed grade 3 treatment-related adverse events, including elevated hepatic transaminases, axillary pain, back pain, joint swelling, colitis, and nephrotic syndrome. Two patients stopped treatment because of adverse effects, but there were no grade 4 events or deaths related to treatment, and no treatment-induced cases of hepatitis, hypophysitis, or uveitis, the researchers noted.

Merck, maker of pembrolizumab, funded the study. Dr. Armand reported financial ties to Merck, Bristol-Myers Squibb, Infinity Pharmaceuticals, Sequenta, Tensha Therapeutics, and Sigma-Tau. Senior author Craig Moskowitz, MD, and five coinvestigators disclosed consulting or advisory relationships or employment with Merck.

PD-1 checkpoint blockade via pembrolizumab is a potential option for classical Hodgkin’s lymphoma that progressed despite brentuximab vedotin therapy, based on a phase Ib, single-arm, open-label, industry-sponsored study of 31 patients.

After a median follow-up of 17 months, five (16%) patients achieved complete remission (90% confidence interval, 7%-31%), and 15 (48%) patients achieved partial remission (90% CI, 33%-64%), for an overall response rate of 65% (48%-79%). Furthermore, 70% of responses lasted at least 24 weeks, reported Philippe Armand, MD, of Dana-Farber Cancer Institute, Boston, and his associates.

“Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies,” they added. “Yet partial responses can be durable, suggesting that the achievement of complete response with checkpoint blockade is not necessary to derive significant clinical benefit.”

Pembrolizumab (Keytruda) is a humanized, highly selective IgG4 anti-PD-1 (programmed death-1) monoclonal antibody approved in the United States for patients with unresectable or metastatic melanoma or metastatic PDL-1 expressing non–small cell lung cancer. Tumor cells in classical Hodgkin lymphoma (HL) often overexpress PD-1 ligands, which “strongly suggests” that HL is PD-1 dependent, the researchers noted (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

The researchers analyzed data for one group of patients within a phase Ib study of pembrolizumab in hematologic malignancies (KEYNOTE-013; NCT01953692). These 31 adults (median age, 32 years; 58% male) all had heavily pretreated classical HL – more than half had received at least five prior lines of therapy, and all had progressed on or after brentuximab vedotin therapy. Most patients (71%) also had received autologous stem cell transplantation. All 31 patients in the study received intravenous pembrolizumab (10 mg/kg) every other week.

Rates of progression-free survival were 69% at 24 weeks and 46% at 52 weeks, the researchers said. “Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways,” they reported. Those findings indicate that PD-1 blockade activates T-cell and IFN-gamma signaling pathways, which provides “a compelling rationale for the further development of PD-1 blockade in HL,” they concluded.

The most common treatment-related adverse effects were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Five patients (16%) developed grade 3 treatment-related adverse events, including elevated hepatic transaminases, axillary pain, back pain, joint swelling, colitis, and nephrotic syndrome. Two patients stopped treatment because of adverse effects, but there were no grade 4 events or deaths related to treatment, and no treatment-induced cases of hepatitis, hypophysitis, or uveitis, the researchers noted.

Merck, maker of pembrolizumab, funded the study. Dr. Armand reported financial ties to Merck, Bristol-Myers Squibb, Infinity Pharmaceuticals, Sequenta, Tensha Therapeutics, and Sigma-Tau. Senior author Craig Moskowitz, MD, and five coinvestigators disclosed consulting or advisory relationships or employment with Merck.

PD-1 checkpoint blockade via pembrolizumab is a potential option for classical Hodgkin’s lymphoma that progressed despite brentuximab vedotin therapy, based on a phase Ib, single-arm, open-label, industry-sponsored study of 31 patients.

After a median follow-up of 17 months, five (16%) patients achieved complete remission (90% confidence interval, 7%-31%), and 15 (48%) patients achieved partial remission (90% CI, 33%-64%), for an overall response rate of 65% (48%-79%). Furthermore, 70% of responses lasted at least 24 weeks, reported Philippe Armand, MD, of Dana-Farber Cancer Institute, Boston, and his associates.

“Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies,” they added. “Yet partial responses can be durable, suggesting that the achievement of complete response with checkpoint blockade is not necessary to derive significant clinical benefit.”

Pembrolizumab (Keytruda) is a humanized, highly selective IgG4 anti-PD-1 (programmed death-1) monoclonal antibody approved in the United States for patients with unresectable or metastatic melanoma or metastatic PDL-1 expressing non–small cell lung cancer. Tumor cells in classical Hodgkin lymphoma (HL) often overexpress PD-1 ligands, which “strongly suggests” that HL is PD-1 dependent, the researchers noted (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

The researchers analyzed data for one group of patients within a phase Ib study of pembrolizumab in hematologic malignancies (KEYNOTE-013; NCT01953692). These 31 adults (median age, 32 years; 58% male) all had heavily pretreated classical HL – more than half had received at least five prior lines of therapy, and all had progressed on or after brentuximab vedotin therapy. Most patients (71%) also had received autologous stem cell transplantation. All 31 patients in the study received intravenous pembrolizumab (10 mg/kg) every other week.

Rates of progression-free survival were 69% at 24 weeks and 46% at 52 weeks, the researchers said. “Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways,” they reported. Those findings indicate that PD-1 blockade activates T-cell and IFN-gamma signaling pathways, which provides “a compelling rationale for the further development of PD-1 blockade in HL,” they concluded.

The most common treatment-related adverse effects were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Five patients (16%) developed grade 3 treatment-related adverse events, including elevated hepatic transaminases, axillary pain, back pain, joint swelling, colitis, and nephrotic syndrome. Two patients stopped treatment because of adverse effects, but there were no grade 4 events or deaths related to treatment, and no treatment-induced cases of hepatitis, hypophysitis, or uveitis, the researchers noted.

Merck, maker of pembrolizumab, funded the study. Dr. Armand reported financial ties to Merck, Bristol-Myers Squibb, Infinity Pharmaceuticals, Sequenta, Tensha Therapeutics, and Sigma-Tau. Senior author Craig Moskowitz, MD, and five coinvestigators disclosed consulting or advisory relationships or employment with Merck.

Once-daily oral siponimod was associated with sustained effects on MRI outcomes at 24 months in patients with relapsing-remitting multiple sclerosis in a dose-blinded extension of the phase II study.

Disease activity was low, “with some evidence of greater benefit associated with siponimod at 10-mg, 2-mg, and 1.25-mg doses than with siponimod at 0.25-mg and 0.5-mg doses. No new safety signals emerged, and dose titration at treatment initiation mitigated cardiac effects,” Ludwig Kappos, MD, of University Hospital Basel (Switzerland), and his associates wrote in JAMA Neurology. “With similar efficacy but lower rates of lymphopenia relative to the 10-mg dose, siponimod 2 mg, has been chosen for further development,” they wrote.

Siponimod (BAF312) is a selective sphingosine 1-phosphate receptor (S1P_1,5) modulator that was evaluated for up to 6 months at five doses in the phase II BOLD (BAF312 on MRI Lesion Given Once Daily) study. Patients with relapsing-remitting MS who received 10 mg siponimod had up to 80% reductions in MRI combined unique active lesions (CUALs, or gadolinium-enhancing T1 lesions and/or new and newly enlarging T2 lesions, without double counting), compared with the placebo group. The 2-mg and 0.5-mg dose cohorts had reductions of 72% and 50%, respectively. The current study was a 24-month, dose-blinded extension phase that included 185 participants (73% of 252 eligible patients), of whom 33 patients received 10 mg siponimod, 29 received 2 mg, 43 received 1.25 mg, 29 received 0.5 mg, and 50 received 0.25 mg (JAMA Neurol. 2016 July 5. doi: 10.1001/jamaneurol.2016.1451).

Average reductions in gadolinium-enhancing T1 lesion counts were sustained in the 10-mg, 2-mg, 1.25-mg, and 0.5-mg dose groups at month 24, the researchers reported. The 1.25-mg and 2-mg doses yielded the highest proportions of patients free from new MRI activity (58% for both dose groups) and free from new or newly enlarging T2 lesions (61% and 58%, respectively). New or newly enlarging T2 lesions were numerically lower at doses exceeding 0.25 mg. “There were no clear changes in normalized brain volume within or between any of the treatment groups,” the investigators added.

Dose titration during the first 10 days of treatment mitigated bradycardia and atrioventricular conduction effects. Rates of adverse events within dose groups ranged from 84% to 97% and did not show a trend with dose size. Serious adverse events affected nine patients (5%) and included one case each of otosclerosis, gastritis, anaphylaxis, acute pyelonephritis, femoral and ankle fractures, basal cell carcinoma, cervical neoplasm, and abortion. Thirteen patients (7%) required treatment interruptions because of adverse events, of which seven consisted of lymphopenia or decreased lymphocyte count at the 10-mg dose. Other adverse events leading to dose interruptions or adjustments included neutropenia, upper respiratory tract infection, elevated hepatic transaminases, and hypertension.

Novartis is developing siponimod and funded the study. Coinvestigators employed by Novartis participated in all aspects of the study, including interpretation of the data and manuscript submission. Dr. Kappos disclosed financial ties to Novartis and numerous other pharmaceutical companies, foundations, and societies.

Once-daily oral siponimod was associated with sustained effects on MRI outcomes at 24 months in patients with relapsing-remitting multiple sclerosis in a dose-blinded extension of the phase II study.

Disease activity was low, “with some evidence of greater benefit associated with siponimod at 10-mg, 2-mg, and 1.25-mg doses than with siponimod at 0.25-mg and 0.5-mg doses. No new safety signals emerged, and dose titration at treatment initiation mitigated cardiac effects,” Ludwig Kappos, MD, of University Hospital Basel (Switzerland), and his associates wrote in JAMA Neurology. “With similar efficacy but lower rates of lymphopenia relative to the 10-mg dose, siponimod 2 mg, has been chosen for further development,” they wrote.

Siponimod (BAF312) is a selective sphingosine 1-phosphate receptor (S1P_1,5) modulator that was evaluated for up to 6 months at five doses in the phase II BOLD (BAF312 on MRI Lesion Given Once Daily) study. Patients with relapsing-remitting MS who received 10 mg siponimod had up to 80% reductions in MRI combined unique active lesions (CUALs, or gadolinium-enhancing T1 lesions and/or new and newly enlarging T2 lesions, without double counting), compared with the placebo group. The 2-mg and 0.5-mg dose cohorts had reductions of 72% and 50%, respectively. The current study was a 24-month, dose-blinded extension phase that included 185 participants (73% of 252 eligible patients), of whom 33 patients received 10 mg siponimod, 29 received 2 mg, 43 received 1.25 mg, 29 received 0.5 mg, and 50 received 0.25 mg (JAMA Neurol. 2016 July 5. doi: 10.1001/jamaneurol.2016.1451).

Average reductions in gadolinium-enhancing T1 lesion counts were sustained in the 10-mg, 2-mg, 1.25-mg, and 0.5-mg dose groups at month 24, the researchers reported. The 1.25-mg and 2-mg doses yielded the highest proportions of patients free from new MRI activity (58% for both dose groups) and free from new or newly enlarging T2 lesions (61% and 58%, respectively). New or newly enlarging T2 lesions were numerically lower at doses exceeding 0.25 mg. “There were no clear changes in normalized brain volume within or between any of the treatment groups,” the investigators added.

Dose titration during the first 10 days of treatment mitigated bradycardia and atrioventricular conduction effects. Rates of adverse events within dose groups ranged from 84% to 97% and did not show a trend with dose size. Serious adverse events affected nine patients (5%) and included one case each of otosclerosis, gastritis, anaphylaxis, acute pyelonephritis, femoral and ankle fractures, basal cell carcinoma, cervical neoplasm, and abortion. Thirteen patients (7%) required treatment interruptions because of adverse events, of which seven consisted of lymphopenia or decreased lymphocyte count at the 10-mg dose. Other adverse events leading to dose interruptions or adjustments included neutropenia, upper respiratory tract infection, elevated hepatic transaminases, and hypertension.

Novartis is developing siponimod and funded the study. Coinvestigators employed by Novartis participated in all aspects of the study, including interpretation of the data and manuscript submission. Dr. Kappos disclosed financial ties to Novartis and numerous other pharmaceutical companies, foundations, and societies.

Once-daily oral siponimod was associated with sustained effects on MRI outcomes at 24 months in patients with relapsing-remitting multiple sclerosis in a dose-blinded extension of the phase II study.

Disease activity was low, “with some evidence of greater benefit associated with siponimod at 10-mg, 2-mg, and 1.25-mg doses than with siponimod at 0.25-mg and 0.5-mg doses. No new safety signals emerged, and dose titration at treatment initiation mitigated cardiac effects,” Ludwig Kappos, MD, of University Hospital Basel (Switzerland), and his associates wrote in JAMA Neurology. “With similar efficacy but lower rates of lymphopenia relative to the 10-mg dose, siponimod 2 mg, has been chosen for further development,” they wrote.

Siponimod (BAF312) is a selective sphingosine 1-phosphate receptor (S1P_1,5) modulator that was evaluated for up to 6 months at five doses in the phase II BOLD (BAF312 on MRI Lesion Given Once Daily) study. Patients with relapsing-remitting MS who received 10 mg siponimod had up to 80% reductions in MRI combined unique active lesions (CUALs, or gadolinium-enhancing T1 lesions and/or new and newly enlarging T2 lesions, without double counting), compared with the placebo group. The 2-mg and 0.5-mg dose cohorts had reductions of 72% and 50%, respectively. The current study was a 24-month, dose-blinded extension phase that included 185 participants (73% of 252 eligible patients), of whom 33 patients received 10 mg siponimod, 29 received 2 mg, 43 received 1.25 mg, 29 received 0.5 mg, and 50 received 0.25 mg (JAMA Neurol. 2016 July 5. doi: 10.1001/jamaneurol.2016.1451).

Average reductions in gadolinium-enhancing T1 lesion counts were sustained in the 10-mg, 2-mg, 1.25-mg, and 0.5-mg dose groups at month 24, the researchers reported. The 1.25-mg and 2-mg doses yielded the highest proportions of patients free from new MRI activity (58% for both dose groups) and free from new or newly enlarging T2 lesions (61% and 58%, respectively). New or newly enlarging T2 lesions were numerically lower at doses exceeding 0.25 mg. “There were no clear changes in normalized brain volume within or between any of the treatment groups,” the investigators added.

Dose titration during the first 10 days of treatment mitigated bradycardia and atrioventricular conduction effects. Rates of adverse events within dose groups ranged from 84% to 97% and did not show a trend with dose size. Serious adverse events affected nine patients (5%) and included one case each of otosclerosis, gastritis, anaphylaxis, acute pyelonephritis, femoral and ankle fractures, basal cell carcinoma, cervical neoplasm, and abortion. Thirteen patients (7%) required treatment interruptions because of adverse events, of which seven consisted of lymphopenia or decreased lymphocyte count at the 10-mg dose. Other adverse events leading to dose interruptions or adjustments included neutropenia, upper respiratory tract infection, elevated hepatic transaminases, and hypertension.

Novartis is developing siponimod and funded the study. Coinvestigators employed by Novartis participated in all aspects of the study, including interpretation of the data and manuscript submission. Dr. Kappos disclosed financial ties to Novartis and numerous other pharmaceutical companies, foundations, and societies.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

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Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

SCOTTSDALE, ARIZ. – Children and adolescents receiving methotrexate for psoriasis were significantly less likely to experience gastrointestinal side effects when they took a folate supplement every day instead of once weekly or 6 days a week, in a retrospective study of more than 400 pediatric psoriasis patients.

Laboratory abnormalities were significantly more common among children who received a folate supplement 6 days per week rather than daily, noted Inge Bronckers of the department of dermatology, Radboud University, Nijmegen, the Netherlands. “These results support the use of daily folate” in this group of patients,” she said in a poster presentation at the annual meeting of the Society for Investigative Dermatology.

thinkstockphotos.com

Few studies have examined patterns of use or adverse effects of pediatric psoriasis therapies. Although methotrexate is a folate antagonist with related toxicities, whether folate supplementation counteracts the efficacy of methotrexate is also unclear. Because of these uncertainties, some clinicians recommend a supplement 6 days per week, avoiding the day methotrexate is given, while others recommend it daily or once weekly.

To better understand the effects of these regimens, Ms. Inge and her coinvestigators studied 446 children and adolescents who received phototherapy or systemic treatments for moderate to severe psoriasis at 20 centers in the United States, Canada, and Europe between 1990 and 2014. The patients’ average age was 8 years (standard deviation, 4 years); 238 were female and 208 were male.

Among the 390 patients receiving systemic medications, almost 70% were receiving methotrexate, while 27% were being treated with etanercept or another biologic, 15% were using retinoids, 8% were using cyclosporine, and 5% were using fumaric acid. About 19% of patients were receiving more than one of these medications. Methotrexate most often led to nausea (affecting 18% of patients), elevated hepatic transaminases (13%), dyspepsia (7%), and infections (4%), usually of the skin and upper airways. In contrast, biologics most often caused injection-site reactions (19%) and upper airways infections (10%).

Most (253) of the 270 patients on methotrexate had been prescribed folic acid, typically at a dose of about 8 mg/wk, and nearly always in the form of pure folic acid, rather than a multivitamin. Of the patients taking folic acid, about 34% took it 6 days per week, 34% received it daily and 30% – including most patients in Europe – received it once weekly.

Notably, the odds of gastrointestinal side effects were 75% lower for patients who received folic acid daily or 6 days per week, compared with those who received folic acid once a week (odds ratio, 0.25, in both cases; P less than .001), the investigators found. However, laboratory abnormalities were significantly more likely when folic acid was given 6 days a week, compared with daily (OR, 2.31; P = .03) or weekly (OR, 3.9; P = .002). Patients in Europe, who usually received folic acid weekly, were significantly more likely to have methotrexate-related gastrointestinal side effects than were patients in North America (OR, 3.4; P less than .001), and were less likely to have laboratory abnormalities (OR, 0.32; P = .004).

Patients on biologic therapy were less likely to develop laboratory abnormalities or stop treatment because of side effects than were those on other systemic therapies, Ms. Inge and her associates found. Because methotrexate was associated with elevated liver enzymes, it also was dose adjusted more often than other therapies. No patient on any therapy was diagnosed with tuberculosis or malignancy, but three patients on methotrexate had severe adverse effects, including liver disease, methotrexate hypersensitivity pneumonitis, and severe personality changes. In contrast, fumarate was associated with one case each of pericarditis and bone marrow suppression, while one patient on the biologic adalimumab developed appendicitis.

The study underscores the need to monitor the long-term risks of pediatric psoriasis treatments, the researchers concluded. Data and lessons from the study are being used to develop a prospective pediatric psoriasis registry. “If industry joins forces to use this prospective international registry to capture prospective pediatric data, we will ensure early detection of safety signals and facilitate comparative analyses of efficacy and safety,” Ms. Inge said in the poster.

The International Psoriasis Council funded the study. The investigators did not list disclosures.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

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Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

Integrins that bind arginine-glycine-aspartic acid (RGD) activated stellate cells in the pancreas, inducing pancreatic fibrogenesis in mice, researchers reported in the July issue of Cellular and Molecular Gastroenterology and Hepatology.

“Small-molecule antagonists of this interaction might be developed for the treatment of pancreatic fibrotic diseases,” wrote Dr. Barbara Ulmasov and her associates at Saint Louis University.

Cytokine transforming growth factor beta, or TGFB, plays a “central” role in the activation of pancreatic stellate cells and the promotion of fibrogenesis, both in the pancreas and in other organs, the investigators noted. Because latent TGFB is “abundantly present” in the pancreas and most other tissues, it might be more important to control the activation of TGFB than its expression, they added. Studies of other organs have shown that TGFB is activated when integrins of the av family bind the RGD sequence, but no one had determined whether this was true for pancreatic fibrogenesis, Dr. Ulmasov and her associates asserted (Cell Mol Gastroenterol Hepatol. 2016 Mar 16. doi: 10.1016/j.jcmgh.2016.03.004).

Therefore, they repeatedly injected female C57BL/6 mice with cerulein to induce pancreatic fibrogenesis, and gave a group of control mice sterile saline instead. The mice then received continuous infusions of a small molecule called CWHM-12, which is an antagonist of RGD-integrin that is known to prevent both pulmonary and hepatic fibrosis in mice. After euthanizing the mice, the researchers measured pancreatic parenchymal atrophy, fibrosis, and activation of pancreatic stellate cells. They also studied TGFB activation in an established line of pancreatic stellate cells from rats.

Pancreatic stellate cells expressed messenger RNAs encoding RGD-binding integrins, the investigators found. The mice that received cerulein had higher levels of these integrins than the mice that received saline, and the cerulein group also had more disrupted acinar cell architecture, tubular complexes, and infiltrations of inflammatory cells. Mice that received prophylactic CWHM-12 had only somewhat less acinar cell loss and atrophy than the control mice, and had similar levels of inflammatory cell infiltration, but had “dramatically” lower levels of pancreatic fibrosis, the researchers said. Even if mice received CWHM-12 several days after starting cerulein, they still had less fibrosis and activation of TGFB than if they received saline, they noted.

The established line of pancreatic stellate cells “could robustly activate endogenously produced TGFB,” the investigators also reported. Furthermore, CWHM-12 “potently blocked TGFB activation,” unlike the control compound. Taken together, the findings illustrate the “critical role of RGD-binding integrins in chronic pancreatitis, and the promising potential to arrest or possibly even reverse pancreatic fibrosis using a pharmacologic approach to inhibiting integrin-mediated TGFB activation,” the researchers concluded.

The National Pancreas Foundation and the Frank R. Burton Memorial Fund supported the study. Dr. Ulmasov had no disclosures. Three coinvestigators reported being consultants and/or holding equity in Integrin Therapeutics, Nimbus Therapeutics, Bristol-Myers Squibb, Janssen, Mitsubishi Tanabe, Conatus, and Scholar Rock.

Integrins that bind arginine-glycine-aspartic acid (RGD) activated stellate cells in the pancreas, inducing pancreatic fibrogenesis in mice, researchers reported in the July issue of Cellular and Molecular Gastroenterology and Hepatology.

“Small-molecule antagonists of this interaction might be developed for the treatment of pancreatic fibrotic diseases,” wrote Dr. Barbara Ulmasov and her associates at Saint Louis University.

Cytokine transforming growth factor beta, or TGFB, plays a “central” role in the activation of pancreatic stellate cells and the promotion of fibrogenesis, both in the pancreas and in other organs, the investigators noted. Because latent TGFB is “abundantly present” in the pancreas and most other tissues, it might be more important to control the activation of TGFB than its expression, they added. Studies of other organs have shown that TGFB is activated when integrins of the av family bind the RGD sequence, but no one had determined whether this was true for pancreatic fibrogenesis, Dr. Ulmasov and her associates asserted (Cell Mol Gastroenterol Hepatol. 2016 Mar 16. doi: 10.1016/j.jcmgh.2016.03.004).

Therefore, they repeatedly injected female C57BL/6 mice with cerulein to induce pancreatic fibrogenesis, and gave a group of control mice sterile saline instead. The mice then received continuous infusions of a small molecule called CWHM-12, which is an antagonist of RGD-integrin that is known to prevent both pulmonary and hepatic fibrosis in mice. After euthanizing the mice, the researchers measured pancreatic parenchymal atrophy, fibrosis, and activation of pancreatic stellate cells. They also studied TGFB activation in an established line of pancreatic stellate cells from rats.

Pancreatic stellate cells expressed messenger RNAs encoding RGD-binding integrins, the investigators found. The mice that received cerulein had higher levels of these integrins than the mice that received saline, and the cerulein group also had more disrupted acinar cell architecture, tubular complexes, and infiltrations of inflammatory cells. Mice that received prophylactic CWHM-12 had only somewhat less acinar cell loss and atrophy than the control mice, and had similar levels of inflammatory cell infiltration, but had “dramatically” lower levels of pancreatic fibrosis, the researchers said. Even if mice received CWHM-12 several days after starting cerulein, they still had less fibrosis and activation of TGFB than if they received saline, they noted.

The established line of pancreatic stellate cells “could robustly activate endogenously produced TGFB,” the investigators also reported. Furthermore, CWHM-12 “potently blocked TGFB activation,” unlike the control compound. Taken together, the findings illustrate the “critical role of RGD-binding integrins in chronic pancreatitis, and the promising potential to arrest or possibly even reverse pancreatic fibrosis using a pharmacologic approach to inhibiting integrin-mediated TGFB activation,” the researchers concluded.

The National Pancreas Foundation and the Frank R. Burton Memorial Fund supported the study. Dr. Ulmasov had no disclosures. Three coinvestigators reported being consultants and/or holding equity in Integrin Therapeutics, Nimbus Therapeutics, Bristol-Myers Squibb, Janssen, Mitsubishi Tanabe, Conatus, and Scholar Rock.

Integrins that bind arginine-glycine-aspartic acid (RGD) activated stellate cells in the pancreas, inducing pancreatic fibrogenesis in mice, researchers reported in the July issue of Cellular and Molecular Gastroenterology and Hepatology.

“Small-molecule antagonists of this interaction might be developed for the treatment of pancreatic fibrotic diseases,” wrote Dr. Barbara Ulmasov and her associates at Saint Louis University.

Cytokine transforming growth factor beta, or TGFB, plays a “central” role in the activation of pancreatic stellate cells and the promotion of fibrogenesis, both in the pancreas and in other organs, the investigators noted. Because latent TGFB is “abundantly present” in the pancreas and most other tissues, it might be more important to control the activation of TGFB than its expression, they added. Studies of other organs have shown that TGFB is activated when integrins of the av family bind the RGD sequence, but no one had determined whether this was true for pancreatic fibrogenesis, Dr. Ulmasov and her associates asserted (Cell Mol Gastroenterol Hepatol. 2016 Mar 16. doi: 10.1016/j.jcmgh.2016.03.004).

Therefore, they repeatedly injected female C57BL/6 mice with cerulein to induce pancreatic fibrogenesis, and gave a group of control mice sterile saline instead. The mice then received continuous infusions of a small molecule called CWHM-12, which is an antagonist of RGD-integrin that is known to prevent both pulmonary and hepatic fibrosis in mice. After euthanizing the mice, the researchers measured pancreatic parenchymal atrophy, fibrosis, and activation of pancreatic stellate cells. They also studied TGFB activation in an established line of pancreatic stellate cells from rats.

Pancreatic stellate cells expressed messenger RNAs encoding RGD-binding integrins, the investigators found. The mice that received cerulein had higher levels of these integrins than the mice that received saline, and the cerulein group also had more disrupted acinar cell architecture, tubular complexes, and infiltrations of inflammatory cells. Mice that received prophylactic CWHM-12 had only somewhat less acinar cell loss and atrophy than the control mice, and had similar levels of inflammatory cell infiltration, but had “dramatically” lower levels of pancreatic fibrosis, the researchers said. Even if mice received CWHM-12 several days after starting cerulein, they still had less fibrosis and activation of TGFB than if they received saline, they noted.

The established line of pancreatic stellate cells “could robustly activate endogenously produced TGFB,” the investigators also reported. Furthermore, CWHM-12 “potently blocked TGFB activation,” unlike the control compound. Taken together, the findings illustrate the “critical role of RGD-binding integrins in chronic pancreatitis, and the promising potential to arrest or possibly even reverse pancreatic fibrosis using a pharmacologic approach to inhibiting integrin-mediated TGFB activation,” the researchers concluded.

The National Pancreas Foundation and the Frank R. Burton Memorial Fund supported the study. Dr. Ulmasov had no disclosures. Three coinvestigators reported being consultants and/or holding equity in Integrin Therapeutics, Nimbus Therapeutics, Bristol-Myers Squibb, Janssen, Mitsubishi Tanabe, Conatus, and Scholar Rock.

Among patients with hepatitis C virus infection who were in compensated cirrhosis, sustained viral response was associated with significantly lower rates of liver decompensation, hepatocellular carcinoma, and liver-related death, even in the presence of clinically meaningful portal hypertension.

But patients in stage 2 cirrhosis were more likely than were stage 1 patients to develop liver decompensation and to die of hepatocellular carcinoma, regardless of SVR, said Dr. Vito Di Marco and his associates at the University of Palermo, Italy. “The available evidence, including our own, suggests that it is opportune to treat HCV as early as possible, in order to reduce progression to stages of cirrhosis in which a viral cure may be less likely lead to ultimate achievement of a major benefit,” they wrote. The report is in the July issue of Gastroenterology.

Clinically significant portal hypertension causes esophageal varices, a “landmark” indicator of stage 2 cirrhosis, the researchers noted. To parse the effects of SVR by cirrhosis stage, they followed all 444 HCV patients with compensated cirrhosis who were treated with pegylated interferon a2b and ribavirin at their tertiary liver centers between 2001 and 2009 (Gastroenterology 2016 March 31. doi: 10.1053/j.gastro.2016.03.036).

The cohort included 218 patients without esophageal varices (that is, patients in stage 1 cirrhosis) and 226 patients with esophageal varices (stage 2 cirrhosis), the researchers said. The groups were demographically similar at baseline, and had similar body mass indices and rates of comorbidities. Rates of SVR were 31% for patients in stage 1 cirrhosis and 18% for patients in stage 2 cirrhosis (P = .003).

Among stage 1 patients, achieving SVR was associated with a lower risk of liver decompensation (0% versus 7%; P = .009), a lower annual rate of hepatocellular carcinoma (0.7% versus 2.9%; P = .002), and a lower risk of liver-related death (3% versus 12%; P = .03). Stage 1 cirrhosis patients also were about 75% less likely to develop esophageal varices if they achieved SVR than if they did not (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11 to 0.48; P less than .001).

Eradicating HCV infection also was associated with better clinical outcomes among patients in stage 2 cirrhosis, according to the investigators. For example, those who achieved SVR had a 0.9% annual rate of hepatocellular carcinoma, compared with 3.6% for those who did not (P = .002). And only 2% of stage 2 patients who achieved SVR died from hepatocellular carcinoma, compared to 18% of those who did not (P = .003).

But regardless of SVR, patients with stage 2 cirrhosis were nearly three times more likely to develop liver compensation (HR, 2.8; 95% CI, 1.73 to 4.59) and about 1.75 times more likely to die of liver-related causes (HR, 1.77; 95% CI, 1.12 to 2.80) compared with patients in stage 1 cirrhosis, the investigators emphasized. Also, achieving SVR did not prevent stage 2 patients from developing more esophageal varices (HR, 1.58; 95% CI, 0.33 to 1.03).

The researchers acknowledged several study limitations. “We have performed many comparisons with respect to multiple endpoints, which could have increased the likelihood of inference errors that can result from multiple comparisons,” they wrote. “Furthermore, we cannot exclude the lack of power as an explanation for some of our results.” In addition, pegylated interferon–based therapies have low rates of SVR, and the study was limited to patients who could tolerate the regimen, they added. Nonetheless, the results indicate that eradicating HCV is clinically beneficial even in advanced compensated cirrhosis, but that early treatment helps maximize these outcomes, they concluded. “Pegylated interferon–free direct-acting antiviral combo regimens will ultimately increase the rate of virological cure to almost universal effectiveness,” they added. “It remains to be assessed whether the effectiveness of these new regimens will be automatically translated into a universal clinical benefit.”

The Italian Ministry of Health funded the study. The investigators had no disclosures.

Among patients with hepatitis C virus infection who were in compensated cirrhosis, sustained viral response was associated with significantly lower rates of liver decompensation, hepatocellular carcinoma, and liver-related death, even in the presence of clinically meaningful portal hypertension.

But patients in stage 2 cirrhosis were more likely than were stage 1 patients to develop liver decompensation and to die of hepatocellular carcinoma, regardless of SVR, said Dr. Vito Di Marco and his associates at the University of Palermo, Italy. “The available evidence, including our own, suggests that it is opportune to treat HCV as early as possible, in order to reduce progression to stages of cirrhosis in which a viral cure may be less likely lead to ultimate achievement of a major benefit,” they wrote. The report is in the July issue of Gastroenterology.

Clinically significant portal hypertension causes esophageal varices, a “landmark” indicator of stage 2 cirrhosis, the researchers noted. To parse the effects of SVR by cirrhosis stage, they followed all 444 HCV patients with compensated cirrhosis who were treated with pegylated interferon a2b and ribavirin at their tertiary liver centers between 2001 and 2009 (Gastroenterology 2016 March 31. doi: 10.1053/j.gastro.2016.03.036).

The cohort included 218 patients without esophageal varices (that is, patients in stage 1 cirrhosis) and 226 patients with esophageal varices (stage 2 cirrhosis), the researchers said. The groups were demographically similar at baseline, and had similar body mass indices and rates of comorbidities. Rates of SVR were 31% for patients in stage 1 cirrhosis and 18% for patients in stage 2 cirrhosis (P = .003).

Among stage 1 patients, achieving SVR was associated with a lower risk of liver decompensation (0% versus 7%; P = .009), a lower annual rate of hepatocellular carcinoma (0.7% versus 2.9%; P = .002), and a lower risk of liver-related death (3% versus 12%; P = .03). Stage 1 cirrhosis patients also were about 75% less likely to develop esophageal varices if they achieved SVR than if they did not (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11 to 0.48; P less than .001).

Eradicating HCV infection also was associated with better clinical outcomes among patients in stage 2 cirrhosis, according to the investigators. For example, those who achieved SVR had a 0.9% annual rate of hepatocellular carcinoma, compared with 3.6% for those who did not (P = .002). And only 2% of stage 2 patients who achieved SVR died from hepatocellular carcinoma, compared to 18% of those who did not (P = .003).

But regardless of SVR, patients with stage 2 cirrhosis were nearly three times more likely to develop liver compensation (HR, 2.8; 95% CI, 1.73 to 4.59) and about 1.75 times more likely to die of liver-related causes (HR, 1.77; 95% CI, 1.12 to 2.80) compared with patients in stage 1 cirrhosis, the investigators emphasized. Also, achieving SVR did not prevent stage 2 patients from developing more esophageal varices (HR, 1.58; 95% CI, 0.33 to 1.03).

The researchers acknowledged several study limitations. “We have performed many comparisons with respect to multiple endpoints, which could have increased the likelihood of inference errors that can result from multiple comparisons,” they wrote. “Furthermore, we cannot exclude the lack of power as an explanation for some of our results.” In addition, pegylated interferon–based therapies have low rates of SVR, and the study was limited to patients who could tolerate the regimen, they added. Nonetheless, the results indicate that eradicating HCV is clinically beneficial even in advanced compensated cirrhosis, but that early treatment helps maximize these outcomes, they concluded. “Pegylated interferon–free direct-acting antiviral combo regimens will ultimately increase the rate of virological cure to almost universal effectiveness,” they added. “It remains to be assessed whether the effectiveness of these new regimens will be automatically translated into a universal clinical benefit.”

The Italian Ministry of Health funded the study. The investigators had no disclosures.

Among patients with hepatitis C virus infection who were in compensated cirrhosis, sustained viral response was associated with significantly lower rates of liver decompensation, hepatocellular carcinoma, and liver-related death, even in the presence of clinically meaningful portal hypertension.

But patients in stage 2 cirrhosis were more likely than were stage 1 patients to develop liver decompensation and to die of hepatocellular carcinoma, regardless of SVR, said Dr. Vito Di Marco and his associates at the University of Palermo, Italy. “The available evidence, including our own, suggests that it is opportune to treat HCV as early as possible, in order to reduce progression to stages of cirrhosis in which a viral cure may be less likely lead to ultimate achievement of a major benefit,” they wrote. The report is in the July issue of Gastroenterology.

Clinically significant portal hypertension causes esophageal varices, a “landmark” indicator of stage 2 cirrhosis, the researchers noted. To parse the effects of SVR by cirrhosis stage, they followed all 444 HCV patients with compensated cirrhosis who were treated with pegylated interferon a2b and ribavirin at their tertiary liver centers between 2001 and 2009 (Gastroenterology 2016 March 31. doi: 10.1053/j.gastro.2016.03.036).

The cohort included 218 patients without esophageal varices (that is, patients in stage 1 cirrhosis) and 226 patients with esophageal varices (stage 2 cirrhosis), the researchers said. The groups were demographically similar at baseline, and had similar body mass indices and rates of comorbidities. Rates of SVR were 31% for patients in stage 1 cirrhosis and 18% for patients in stage 2 cirrhosis (P = .003).

Among stage 1 patients, achieving SVR was associated with a lower risk of liver decompensation (0% versus 7%; P = .009), a lower annual rate of hepatocellular carcinoma (0.7% versus 2.9%; P = .002), and a lower risk of liver-related death (3% versus 12%; P = .03). Stage 1 cirrhosis patients also were about 75% less likely to develop esophageal varices if they achieved SVR than if they did not (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11 to 0.48; P less than .001).

Eradicating HCV infection also was associated with better clinical outcomes among patients in stage 2 cirrhosis, according to the investigators. For example, those who achieved SVR had a 0.9% annual rate of hepatocellular carcinoma, compared with 3.6% for those who did not (P = .002). And only 2% of stage 2 patients who achieved SVR died from hepatocellular carcinoma, compared to 18% of those who did not (P = .003).

But regardless of SVR, patients with stage 2 cirrhosis were nearly three times more likely to develop liver compensation (HR, 2.8; 95% CI, 1.73 to 4.59) and about 1.75 times more likely to die of liver-related causes (HR, 1.77; 95% CI, 1.12 to 2.80) compared with patients in stage 1 cirrhosis, the investigators emphasized. Also, achieving SVR did not prevent stage 2 patients from developing more esophageal varices (HR, 1.58; 95% CI, 0.33 to 1.03).

The researchers acknowledged several study limitations. “We have performed many comparisons with respect to multiple endpoints, which could have increased the likelihood of inference errors that can result from multiple comparisons,” they wrote. “Furthermore, we cannot exclude the lack of power as an explanation for some of our results.” In addition, pegylated interferon–based therapies have low rates of SVR, and the study was limited to patients who could tolerate the regimen, they added. Nonetheless, the results indicate that eradicating HCV is clinically beneficial even in advanced compensated cirrhosis, but that early treatment helps maximize these outcomes, they concluded. “Pegylated interferon–free direct-acting antiviral combo regimens will ultimately increase the rate of virological cure to almost universal effectiveness,” they added. “It remains to be assessed whether the effectiveness of these new regimens will be automatically translated into a universal clinical benefit.”

The Italian Ministry of Health funded the study. The investigators had no disclosures.

Among patients with immune-mediated diseases and a history of malignancy, cancer recurrence rates were similar regardless of whether they received tumor necrosis factor inhibitors, traditional immunosuppressants, or no immunosuppression, according to a meta-analysis of 16 cohort and case-control studies.

“However, there is a need for larger studies to prospectively monitor for cancer recurrence and new malignancies in this population to better inform our practice,” wrote Dr. Edward Shelton of Massachusetts General Hospital in Boston, and his associates. The report is in the July issue of Gastroenterology.

Patients with immune-mediated diseases often have a history of malignancy, raising questions about the effects of therapies that target the immune system, the researchers noted. However, relevant studies have been “small with few events, preventing robust estimates of risk,” they said. They searched Medline, Embase, and conference proceedings through April 2015 for studies of the risk of primary or recurrent cancer among patients with a history of malignancy who were exposed to thiopurines, methotrexate, or anti-TNF agents, or no immunosuppression. Among the 16 studies meeting these criteria, seven included patients with rheumatoid arthritis, seven included patients with inflammatory bowel disease, one included both diseases, and one included patients with psoriasis. Twelve were cohort studies, one was a case-control study, and three were case series. The resulting meta-analysis comprised 11,702 patients who contributed a total of 31,258 person-years of follow-up (Gastroenterology 2016 May 13. doi: 10.1053/j.gastro.2016.03.037).

Rates of cancer recurrence were statistically similar among patients who received no immunosuppression, anti-TNF therapy, traditional immune modulators, or combination regimens (P greater than .1 for differences among groups). Numerically, however, the risk of recurrent cancer was highest with combination immunotherapy (54.5 cases per 1,000 person-years of follow-up), compared with 37.5 cases per 1,000 person-years for patients who did not receive immunosuppressive treatment, 36.2 cases per 1,000 person-years for patients who received traditional immunomodulator monotherapy, and 33.8 cases per 1,000 person-years for patients who received anti-TNF agents. Analyses of subgroups of patients with new or recurrent cancers, or various types of therapies, and of specific immune-mediated diseases yielded “similar results, with no increase in risk,” said the researchers. Furthermore, rates of cancer recurrence did not statistically differ depending on whether patients started immunosuppression less than or more than 6 years after their index cancer (P = .43).

“Treatment decisions after a cancer diagnosis are complex, and must take into account the natural history of cancer, histologic type and stage, time from diagnosis, and course of underlying chronic inflammatory disease,” the researchers noted. “Our findings suggest that anti-TNF therapy, conventional immunosuppressant therapy, or combination immunosuppression are not associated with an increased risk of cancer recurrence in this population.”

The researchers cited several limitations. Notably, three of the studies included only 20 patients, and the studies included variable index cancers and methods for detecting recurrent cancers. “It also is possible, and likely, that patients who were at high risk for recurrence were not recommenced on immunosuppression, and consequently our findings may be more applicable to a population in which the patient and physicians were comfortable with re-initiation of therapy,” they said.

The National Institutes of Health supported several of the study investigators. Dr. Shelton had no disclosures. Five coinvestigators disclosed relationships with a number of pharmaceutical companies.

Among patients with immune-mediated diseases and a history of malignancy, cancer recurrence rates were similar regardless of whether they received tumor necrosis factor inhibitors, traditional immunosuppressants, or no immunosuppression, according to a meta-analysis of 16 cohort and case-control studies.

“However, there is a need for larger studies to prospectively monitor for cancer recurrence and new malignancies in this population to better inform our practice,” wrote Dr. Edward Shelton of Massachusetts General Hospital in Boston, and his associates. The report is in the July issue of Gastroenterology.

Patients with immune-mediated diseases often have a history of malignancy, raising questions about the effects of therapies that target the immune system, the researchers noted. However, relevant studies have been “small with few events, preventing robust estimates of risk,” they said. They searched Medline, Embase, and conference proceedings through April 2015 for studies of the risk of primary or recurrent cancer among patients with a history of malignancy who were exposed to thiopurines, methotrexate, or anti-TNF agents, or no immunosuppression. Among the 16 studies meeting these criteria, seven included patients with rheumatoid arthritis, seven included patients with inflammatory bowel disease, one included both diseases, and one included patients with psoriasis. Twelve were cohort studies, one was a case-control study, and three were case series. The resulting meta-analysis comprised 11,702 patients who contributed a total of 31,258 person-years of follow-up (Gastroenterology 2016 May 13. doi: 10.1053/j.gastro.2016.03.037).

Rates of cancer recurrence were statistically similar among patients who received no immunosuppression, anti-TNF therapy, traditional immune modulators, or combination regimens (P greater than .1 for differences among groups). Numerically, however, the risk of recurrent cancer was highest with combination immunotherapy (54.5 cases per 1,000 person-years of follow-up), compared with 37.5 cases per 1,000 person-years for patients who did not receive immunosuppressive treatment, 36.2 cases per 1,000 person-years for patients who received traditional immunomodulator monotherapy, and 33.8 cases per 1,000 person-years for patients who received anti-TNF agents. Analyses of subgroups of patients with new or recurrent cancers, or various types of therapies, and of specific immune-mediated diseases yielded “similar results, with no increase in risk,” said the researchers. Furthermore, rates of cancer recurrence did not statistically differ depending on whether patients started immunosuppression less than or more than 6 years after their index cancer (P = .43).

“Treatment decisions after a cancer diagnosis are complex, and must take into account the natural history of cancer, histologic type and stage, time from diagnosis, and course of underlying chronic inflammatory disease,” the researchers noted. “Our findings suggest that anti-TNF therapy, conventional immunosuppressant therapy, or combination immunosuppression are not associated with an increased risk of cancer recurrence in this population.”

The researchers cited several limitations. Notably, three of the studies included only 20 patients, and the studies included variable index cancers and methods for detecting recurrent cancers. “It also is possible, and likely, that patients who were at high risk for recurrence were not recommenced on immunosuppression, and consequently our findings may be more applicable to a population in which the patient and physicians were comfortable with re-initiation of therapy,” they said.

The National Institutes of Health supported several of the study investigators. Dr. Shelton had no disclosures. Five coinvestigators disclosed relationships with a number of pharmaceutical companies.

Among patients with immune-mediated diseases and a history of malignancy, cancer recurrence rates were similar regardless of whether they received tumor necrosis factor inhibitors, traditional immunosuppressants, or no immunosuppression, according to a meta-analysis of 16 cohort and case-control studies.

“However, there is a need for larger studies to prospectively monitor for cancer recurrence and new malignancies in this population to better inform our practice,” wrote Dr. Edward Shelton of Massachusetts General Hospital in Boston, and his associates. The report is in the July issue of Gastroenterology.

Patients with immune-mediated diseases often have a history of malignancy, raising questions about the effects of therapies that target the immune system, the researchers noted. However, relevant studies have been “small with few events, preventing robust estimates of risk,” they said. They searched Medline, Embase, and conference proceedings through April 2015 for studies of the risk of primary or recurrent cancer among patients with a history of malignancy who were exposed to thiopurines, methotrexate, or anti-TNF agents, or no immunosuppression. Among the 16 studies meeting these criteria, seven included patients with rheumatoid arthritis, seven included patients with inflammatory bowel disease, one included both diseases, and one included patients with psoriasis. Twelve were cohort studies, one was a case-control study, and three were case series. The resulting meta-analysis comprised 11,702 patients who contributed a total of 31,258 person-years of follow-up (Gastroenterology 2016 May 13. doi: 10.1053/j.gastro.2016.03.037).

Rates of cancer recurrence were statistically similar among patients who received no immunosuppression, anti-TNF therapy, traditional immune modulators, or combination regimens (P greater than .1 for differences among groups). Numerically, however, the risk of recurrent cancer was highest with combination immunotherapy (54.5 cases per 1,000 person-years of follow-up), compared with 37.5 cases per 1,000 person-years for patients who did not receive immunosuppressive treatment, 36.2 cases per 1,000 person-years for patients who received traditional immunomodulator monotherapy, and 33.8 cases per 1,000 person-years for patients who received anti-TNF agents. Analyses of subgroups of patients with new or recurrent cancers, or various types of therapies, and of specific immune-mediated diseases yielded “similar results, with no increase in risk,” said the researchers. Furthermore, rates of cancer recurrence did not statistically differ depending on whether patients started immunosuppression less than or more than 6 years after their index cancer (P = .43).

“Treatment decisions after a cancer diagnosis are complex, and must take into account the natural history of cancer, histologic type and stage, time from diagnosis, and course of underlying chronic inflammatory disease,” the researchers noted. “Our findings suggest that anti-TNF therapy, conventional immunosuppressant therapy, or combination immunosuppression are not associated with an increased risk of cancer recurrence in this population.”

The researchers cited several limitations. Notably, three of the studies included only 20 patients, and the studies included variable index cancers and methods for detecting recurrent cancers. “It also is possible, and likely, that patients who were at high risk for recurrence were not recommenced on immunosuppression, and consequently our findings may be more applicable to a population in which the patient and physicians were comfortable with re-initiation of therapy,” they said.

The National Institutes of Health supported several of the study investigators. Dr. Shelton had no disclosures. Five coinvestigators disclosed relationships with a number of pharmaceutical companies.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

State Medicaid programs denied nearly half of requests to cover direct-acting antiviral drugs for patients with chronic hepatitis C virus (HCV) infection, according to a prospective study of beneficiaries in Delaware, Maryland, New Jersey, and Pennsylvania reported in the July issue of Clinical Gastroenterology and Hepatology.

In contrast, only 5% of Medicare patients and 10% of privately insured patients were denied coverage, said Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, together with his associates. “Notably, nearly one-quarter of Medicaid recipients with cirrhosis experienced treatment denial. Medicaid patients from these states also experienced a longer time to prescription fill than those with Medicare or commercial insurance,” the researchers said.

©roxanabalint/Thinkstock

Their study included 2,321 HCV patients prescribed a direct-acting antiviral regimen between November 1, 2014 and April 30, 2015. All prescriptions were submitted to a specialty pharmacy that serves HCV patients in Maryland, Pennsylvania, Delaware, and New Jersey, the investigators noted. They focused on “absolute denial,” meaning that the prescription was never filled because the insurer denied coverage, regardless of appeals. “Data are lacking on the incidence of absolute denial of direct-acting antiviral prescriptions and factors associated with this outcome,” the investigators said. “These data are important because absolute denial of HCV treatment by insurers might have adverse outcomes on patients and could harm patient-provider relationships” (Clin Gastroenterol Hepatol. 2016 Apr 5. doi: 10.1016/j.cgh.2016.03.040).

Source: American Gastroenterological Association

A total of 1,023 study patients were privately insured, 795 were enrolled in Medicare, and 503 were Medicaid patients, according to the researchers. In all, 377 patients (16%) received absolute denials, most often because of “insufficient information to assess medical need” (36% of denials) and “lack of medical necessity” (35%). Medicaid patients faced an absolute denial rate of 46% – significantly higher than rates for private insurers (10.5%) or Medicare (5%; P less than .001 for both comparisons). After adjusting for potential confounders, Medicaid patients were more than four times as likely to be denied coverage for direct-acting antivirals, compared with privately insured patients (relative risk, 4.1; 95% confidence interval, 3.4-5.1). Delaware’s Medicaid program had the highest rate of absolute denial (57%), followed by Pennsylvania (48%), Maryland (47%), and New Jersey (37%).

Medicaid programs even refused to cover direct-acting antiviral prescriptions for 25% of patients who had cirrhosis, compared with absolute denial rates of only 1% for Medicare and 3% of private insurers (P less than .001 for both comparisons), according to the researchers. The implications of these denials “remain unknown,” but lack of treatment increases the risk of end-stage liver disease, hepatocellular carcinoma, extrahepatic disease, HCV transmission, and “anxiety and stress about HCV disease progression, [which can] provoke distrust among patients of the health care system and their providers,” they added. “Clinicians then are challenged to explain the denial, and important opportunities for patient engagement, education, and cure could be irrevocably lost.”

Medicaid programs also initially denied about 25% of prescriptions before eventually approving them, despite the fact that “patients had complete prior authorization requests that should have contained the materials needed to justify approval,” said the investigators. Furthermore, denial letters usually did not specify the information that was needed, “making it difficult [for clinicians] to appeal the decision.” In contrast, only about 8% of privately insured patients and 13% of Medicare enrollees were initially denied coverage.

Prescriptions as a whole were more likely to be filled in the last 3 months of the study than earlier, perhaps because insurers are starting to relax their reimbursement criteria, said the investigators. Indeed, in October 2015, the American Association for the Study of Liver Diseases and the Infectious Disease Society of America stopped triaging groups of patients for direct-acting antiviral therapy, they noted.

The research was supported by the Penn Center for AIDS Research, which is funded by the National Institutes of Health. Dr. Lo Re received investigator-initiated research support from AstraZeneca. Five coinvestigators reported relationships with a number of pharmaceutical companies. Four coinvestigators reported employment by the study site, Burman’s Specialty Pharmacy. The other four coauthors had no disclosures.

State Medicaid programs denied nearly half of requests to cover direct-acting antiviral drugs for patients with chronic hepatitis C virus (HCV) infection, according to a prospective study of beneficiaries in Delaware, Maryland, New Jersey, and Pennsylvania reported in the July issue of Clinical Gastroenterology and Hepatology.

In contrast, only 5% of Medicare patients and 10% of privately insured patients were denied coverage, said Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, together with his associates. “Notably, nearly one-quarter of Medicaid recipients with cirrhosis experienced treatment denial. Medicaid patients from these states also experienced a longer time to prescription fill than those with Medicare or commercial insurance,” the researchers said.

©roxanabalint/Thinkstock

Their study included 2,321 HCV patients prescribed a direct-acting antiviral regimen between November 1, 2014 and April 30, 2015. All prescriptions were submitted to a specialty pharmacy that serves HCV patients in Maryland, Pennsylvania, Delaware, and New Jersey, the investigators noted. They focused on “absolute denial,” meaning that the prescription was never filled because the insurer denied coverage, regardless of appeals. “Data are lacking on the incidence of absolute denial of direct-acting antiviral prescriptions and factors associated with this outcome,” the investigators said. “These data are important because absolute denial of HCV treatment by insurers might have adverse outcomes on patients and could harm patient-provider relationships” (Clin Gastroenterol Hepatol. 2016 Apr 5. doi: 10.1016/j.cgh.2016.03.040).

Source: American Gastroenterological Association

A total of 1,023 study patients were privately insured, 795 were enrolled in Medicare, and 503 were Medicaid patients, according to the researchers. In all, 377 patients (16%) received absolute denials, most often because of “insufficient information to assess medical need” (36% of denials) and “lack of medical necessity” (35%). Medicaid patients faced an absolute denial rate of 46% – significantly higher than rates for private insurers (10.5%) or Medicare (5%; P less than .001 for both comparisons). After adjusting for potential confounders, Medicaid patients were more than four times as likely to be denied coverage for direct-acting antivirals, compared with privately insured patients (relative risk, 4.1; 95% confidence interval, 3.4-5.1). Delaware’s Medicaid program had the highest rate of absolute denial (57%), followed by Pennsylvania (48%), Maryland (47%), and New Jersey (37%).

Medicaid programs even refused to cover direct-acting antiviral prescriptions for 25% of patients who had cirrhosis, compared with absolute denial rates of only 1% for Medicare and 3% of private insurers (P less than .001 for both comparisons), according to the researchers. The implications of these denials “remain unknown,” but lack of treatment increases the risk of end-stage liver disease, hepatocellular carcinoma, extrahepatic disease, HCV transmission, and “anxiety and stress about HCV disease progression, [which can] provoke distrust among patients of the health care system and their providers,” they added. “Clinicians then are challenged to explain the denial, and important opportunities for patient engagement, education, and cure could be irrevocably lost.”

Medicaid programs also initially denied about 25% of prescriptions before eventually approving them, despite the fact that “patients had complete prior authorization requests that should have contained the materials needed to justify approval,” said the investigators. Furthermore, denial letters usually did not specify the information that was needed, “making it difficult [for clinicians] to appeal the decision.” In contrast, only about 8% of privately insured patients and 13% of Medicare enrollees were initially denied coverage.

Prescriptions as a whole were more likely to be filled in the last 3 months of the study than earlier, perhaps because insurers are starting to relax their reimbursement criteria, said the investigators. Indeed, in October 2015, the American Association for the Study of Liver Diseases and the Infectious Disease Society of America stopped triaging groups of patients for direct-acting antiviral therapy, they noted.

The research was supported by the Penn Center for AIDS Research, which is funded by the National Institutes of Health. Dr. Lo Re received investigator-initiated research support from AstraZeneca. Five coinvestigators reported relationships with a number of pharmaceutical companies. Four coinvestigators reported employment by the study site, Burman’s Specialty Pharmacy. The other four coauthors had no disclosures.

State Medicaid programs denied nearly half of requests to cover direct-acting antiviral drugs for patients with chronic hepatitis C virus (HCV) infection, according to a prospective study of beneficiaries in Delaware, Maryland, New Jersey, and Pennsylvania reported in the July issue of Clinical Gastroenterology and Hepatology.

In contrast, only 5% of Medicare patients and 10% of privately insured patients were denied coverage, said Dr. Vincent Lo Re III of the University of Pennsylvania, Philadelphia, together with his associates. “Notably, nearly one-quarter of Medicaid recipients with cirrhosis experienced treatment denial. Medicaid patients from these states also experienced a longer time to prescription fill than those with Medicare or commercial insurance,” the researchers said.

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Their study included 2,321 HCV patients prescribed a direct-acting antiviral regimen between November 1, 2014 and April 30, 2015. All prescriptions were submitted to a specialty pharmacy that serves HCV patients in Maryland, Pennsylvania, Delaware, and New Jersey, the investigators noted. They focused on “absolute denial,” meaning that the prescription was never filled because the insurer denied coverage, regardless of appeals. “Data are lacking on the incidence of absolute denial of direct-acting antiviral prescriptions and factors associated with this outcome,” the investigators said. “These data are important because absolute denial of HCV treatment by insurers might have adverse outcomes on patients and could harm patient-provider relationships” (Clin Gastroenterol Hepatol. 2016 Apr 5. doi: 10.1016/j.cgh.2016.03.040).

Source: American Gastroenterological Association

A total of 1,023 study patients were privately insured, 795 were enrolled in Medicare, and 503 were Medicaid patients, according to the researchers. In all, 377 patients (16%) received absolute denials, most often because of “insufficient information to assess medical need” (36% of denials) and “lack of medical necessity” (35%). Medicaid patients faced an absolute denial rate of 46% – significantly higher than rates for private insurers (10.5%) or Medicare (5%; P less than .001 for both comparisons). After adjusting for potential confounders, Medicaid patients were more than four times as likely to be denied coverage for direct-acting antivirals, compared with privately insured patients (relative risk, 4.1; 95% confidence interval, 3.4-5.1). Delaware’s Medicaid program had the highest rate of absolute denial (57%), followed by Pennsylvania (48%), Maryland (47%), and New Jersey (37%).

Medicaid programs even refused to cover direct-acting antiviral prescriptions for 25% of patients who had cirrhosis, compared with absolute denial rates of only 1% for Medicare and 3% of private insurers (P less than .001 for both comparisons), according to the researchers. The implications of these denials “remain unknown,” but lack of treatment increases the risk of end-stage liver disease, hepatocellular carcinoma, extrahepatic disease, HCV transmission, and “anxiety and stress about HCV disease progression, [which can] provoke distrust among patients of the health care system and their providers,” they added. “Clinicians then are challenged to explain the denial, and important opportunities for patient engagement, education, and cure could be irrevocably lost.”

Medicaid programs also initially denied about 25% of prescriptions before eventually approving them, despite the fact that “patients had complete prior authorization requests that should have contained the materials needed to justify approval,” said the investigators. Furthermore, denial letters usually did not specify the information that was needed, “making it difficult [for clinicians] to appeal the decision.” In contrast, only about 8% of privately insured patients and 13% of Medicare enrollees were initially denied coverage.

Prescriptions as a whole were more likely to be filled in the last 3 months of the study than earlier, perhaps because insurers are starting to relax their reimbursement criteria, said the investigators. Indeed, in October 2015, the American Association for the Study of Liver Diseases and the Infectious Disease Society of America stopped triaging groups of patients for direct-acting antiviral therapy, they noted.

The research was supported by the Penn Center for AIDS Research, which is funded by the National Institutes of Health. Dr. Lo Re received investigator-initiated research support from AstraZeneca. Five coinvestigators reported relationships with a number of pharmaceutical companies. Four coinvestigators reported employment by the study site, Burman’s Specialty Pharmacy. The other four coauthors had no disclosures.