Clinical Edge Journal Scan Commentary

Varying strategies have been evaluated to diagnose and predict risk of prostate cancer more optimally. The presence of local or systemic inflammation has been postulated to be associated with increased risk of the presence and aggressiveness of prostate cancer. Complete blood counts with differential white counts are routinely obtained, and the ratio of platelets to lymphocytes (PLR), neutrophils to lymphocytes (NLR), and monocytes to lymphocytes (MLR) have been proposed as markers of inflammation. In the study by Lee et al., the authors evaluated whether the PLR was associated with benign prostate disease, clinically insignificant prostate cancer (Gleason 6 or lower), or clinically significant prostate cancer (Gleason 7 or higher) in patients undergoing prostate biopsy. In a cohort of 1652 who underwent biopsy, the only significant finding was a lower PLR in patients with clinically significant prostate cancer and a PSA < 10 ng/mL compared with patients having benign disease or clinically insignificant disease.

Rundle et al evaluated whether NLR or MLR in the setting of cancer varied by race, as African American and Black men are at higher risk for prostate cancer than White men. In this case-control study that included 822 cases of prostate cancer and 573 controls, there were no significant differences in the trajectories of NLR or MLR over time between cases or controls in the entire cohort. The NLR and MLR were higher over time for White men without prostate cancer compared with White men with prostate cancer; however, no such difference was identified when comparing Black men with or without prostate cancer. Thus, while there may be some association between inflammation and prostate cancer diagnoses or risk of aggressiveness, the use of PLR, NLR, or MLR requires much more study to fully determine the usefulness of these ratios.

A slightly different approach to improve diagnostic strategies has been to utilize prostate MRI to identify areas of the prostate suggestive of cancer. Eklund et al evaluated the use of MRI in the setting of an organized prostate screening program. The use of MRI with targeted and standard biopsy was noninferior to standard biopsy alone in detecting clinically significant prostate cancer while fewer clinically insignificant prostate cancers were identified in the MRI with targeted and standard biopsy group compared with the standard biopsy group. This study further supports the increasing utilization of MRI as part of a biopsy approach in men at risk for prostate cancer.

Varying strategies have been evaluated to diagnose and predict risk of prostate cancer more optimally. The presence of local or systemic inflammation has been postulated to be associated with increased risk of the presence and aggressiveness of prostate cancer. Complete blood counts with differential white counts are routinely obtained, and the ratio of platelets to lymphocytes (PLR), neutrophils to lymphocytes (NLR), and monocytes to lymphocytes (MLR) have been proposed as markers of inflammation. In the study by Lee et al., the authors evaluated whether the PLR was associated with benign prostate disease, clinically insignificant prostate cancer (Gleason 6 or lower), or clinically significant prostate cancer (Gleason 7 or higher) in patients undergoing prostate biopsy. In a cohort of 1652 who underwent biopsy, the only significant finding was a lower PLR in patients with clinically significant prostate cancer and a PSA < 10 ng/mL compared with patients having benign disease or clinically insignificant disease.

Rundle et al evaluated whether NLR or MLR in the setting of cancer varied by race, as African American and Black men are at higher risk for prostate cancer than White men. In this case-control study that included 822 cases of prostate cancer and 573 controls, there were no significant differences in the trajectories of NLR or MLR over time between cases or controls in the entire cohort. The NLR and MLR were higher over time for White men without prostate cancer compared with White men with prostate cancer; however, no such difference was identified when comparing Black men with or without prostate cancer. Thus, while there may be some association between inflammation and prostate cancer diagnoses or risk of aggressiveness, the use of PLR, NLR, or MLR requires much more study to fully determine the usefulness of these ratios.

A slightly different approach to improve diagnostic strategies has been to utilize prostate MRI to identify areas of the prostate suggestive of cancer. Eklund et al evaluated the use of MRI in the setting of an organized prostate screening program. The use of MRI with targeted and standard biopsy was noninferior to standard biopsy alone in detecting clinically significant prostate cancer while fewer clinically insignificant prostate cancers were identified in the MRI with targeted and standard biopsy group compared with the standard biopsy group. This study further supports the increasing utilization of MRI as part of a biopsy approach in men at risk for prostate cancer.

Varying strategies have been evaluated to diagnose and predict risk of prostate cancer more optimally. The presence of local or systemic inflammation has been postulated to be associated with increased risk of the presence and aggressiveness of prostate cancer. Complete blood counts with differential white counts are routinely obtained, and the ratio of platelets to lymphocytes (PLR), neutrophils to lymphocytes (NLR), and monocytes to lymphocytes (MLR) have been proposed as markers of inflammation. In the study by Lee et al., the authors evaluated whether the PLR was associated with benign prostate disease, clinically insignificant prostate cancer (Gleason 6 or lower), or clinically significant prostate cancer (Gleason 7 or higher) in patients undergoing prostate biopsy. In a cohort of 1652 who underwent biopsy, the only significant finding was a lower PLR in patients with clinically significant prostate cancer and a PSA < 10 ng/mL compared with patients having benign disease or clinically insignificant disease.

Rundle et al evaluated whether NLR or MLR in the setting of cancer varied by race, as African American and Black men are at higher risk for prostate cancer than White men. In this case-control study that included 822 cases of prostate cancer and 573 controls, there were no significant differences in the trajectories of NLR or MLR over time between cases or controls in the entire cohort. The NLR and MLR were higher over time for White men without prostate cancer compared with White men with prostate cancer; however, no such difference was identified when comparing Black men with or without prostate cancer. Thus, while there may be some association between inflammation and prostate cancer diagnoses or risk of aggressiveness, the use of PLR, NLR, or MLR requires much more study to fully determine the usefulness of these ratios.

A slightly different approach to improve diagnostic strategies has been to utilize prostate MRI to identify areas of the prostate suggestive of cancer. Eklund et al evaluated the use of MRI in the setting of an organized prostate screening program. The use of MRI with targeted and standard biopsy was noninferior to standard biopsy alone in detecting clinically significant prostate cancer while fewer clinically insignificant prostate cancers were identified in the MRI with targeted and standard biopsy group compared with the standard biopsy group. This study further supports the increasing utilization of MRI as part of a biopsy approach in men at risk for prostate cancer.

Recently, ACR guidelines were published on the prevention and treatment of glucocorticoid-induced osteoporosis, emphasizing use of supplemental calcium and vitamin D and antiresorptive therapy. This randomized, controlled, open-label trial by Cho et al looks at the efficacy of selective estrogen receptor modulators (SERMs) in preventing bone loss and fractures in postmenopausal RA patients with osteopenia on long-term glucocorticoids. Patients were randomized to bazedoxefine, a 3^rd-generation SERM vs no therapy in addition to background calcium and vitamin D supplementation and bone mineral density (BMD) and trabecular bone score (TBS). Bone turnover markers were assessed over the course of 48 weeks, in addition to adverse events. Prednisone dose was relatively low, with a baseline of ~3 mg/day. Bone density increased by almost 2% in the L spine (P < 0.05), but the increases in BMD at the femoral neck and TBS were not significant. Bone turnover markers did decrease in the bazedoxefine group, though not in the control group. These findings are not striking but are promising given the short duration of the study (<1 year), and potentially deserves longer-term follow-up, both for evaluation of efficacy as well as long-term safety. In the US, the medication is only available in combination with estrogen, and thus it is not currently a practical option for RA patients with GIOP.

Despite wider availability of both synthetic and biologic DMARDs for treatment of RA in recent years, persistent pain is an issue for many patients, perhaps due to peripheral sensitization. Though it seems almost unnecessary to investigate the utility of glucocorticoids for treatment of RA-related pain, the magnitude and duration of their benefit is unknown. McWilliams et al take the approach of quantitatively analyzing the benefit of glucocorticoids in RA over time in their systematic review and meta-analysis. The study looked at both spontaneous and evoked pain, and evaluated 65 studies that mostly used pain visual analogue scale, tender joint count, and Ritchie Articular Index. Reduction in spontaneous pain was greatest in the 0-3-month time period, with smaller reductions in 3-6 months and >6 month. A similar pattern was seen in evaluation of the time course of evoked pain. As such, the benefits of long-term systemic glucocorticoid therapy may not outweigh its well-known risks, especially in patients with persistent pain. Whether this is due to non-inflammatory sources of pain or other mechanisms remains unknown and is likely heavily impacted by the specific clinical scenario.

Due to the potential long-terms side effects of chronic immunosuppression, including long-term glucocorticoid therapy in patients with persistent pain in RA, the course and predictors of unacceptable pain are of interest. Eberhard et al examined an inception cohort of RA patients in a single center in Sweden over the course of 5 years. They were found to have reduction of VAS pain from inclusion to 6 months, but pain levels largely stayed the same during the rest of the follow-up period. The proportion of patients with unacceptable pain also decreased but remained stable at about 30% after 1 year, with 20% having unacceptable pain and low inflammation and about 10% having high inflammation and unacceptable pain. The study found seropositivity, high inflammatory parameters, high DAS28 and severe patient-reported outcomes to be predictive of high inflammation and unacceptable pain and lower age, higher VAS pain, and low ESR to be predictive of low inflammation and unacceptable pain. These findings highlight the importance of examining non-inflammatory mechanisms of pain as well as identifying treatments; however, in evaluating the risk of immunosuppression and glucocorticoid therapy, it does not guide increasing or reducing treatment in RA patients with persistent pain.

Recently, ACR guidelines were published on the prevention and treatment of glucocorticoid-induced osteoporosis, emphasizing use of supplemental calcium and vitamin D and antiresorptive therapy. This randomized, controlled, open-label trial by Cho et al looks at the efficacy of selective estrogen receptor modulators (SERMs) in preventing bone loss and fractures in postmenopausal RA patients with osteopenia on long-term glucocorticoids. Patients were randomized to bazedoxefine, a 3^rd-generation SERM vs no therapy in addition to background calcium and vitamin D supplementation and bone mineral density (BMD) and trabecular bone score (TBS). Bone turnover markers were assessed over the course of 48 weeks, in addition to adverse events. Prednisone dose was relatively low, with a baseline of ~3 mg/day. Bone density increased by almost 2% in the L spine (P < 0.05), but the increases in BMD at the femoral neck and TBS were not significant. Bone turnover markers did decrease in the bazedoxefine group, though not in the control group. These findings are not striking but are promising given the short duration of the study (<1 year), and potentially deserves longer-term follow-up, both for evaluation of efficacy as well as long-term safety. In the US, the medication is only available in combination with estrogen, and thus it is not currently a practical option for RA patients with GIOP.

Despite wider availability of both synthetic and biologic DMARDs for treatment of RA in recent years, persistent pain is an issue for many patients, perhaps due to peripheral sensitization. Though it seems almost unnecessary to investigate the utility of glucocorticoids for treatment of RA-related pain, the magnitude and duration of their benefit is unknown. McWilliams et al take the approach of quantitatively analyzing the benefit of glucocorticoids in RA over time in their systematic review and meta-analysis. The study looked at both spontaneous and evoked pain, and evaluated 65 studies that mostly used pain visual analogue scale, tender joint count, and Ritchie Articular Index. Reduction in spontaneous pain was greatest in the 0-3-month time period, with smaller reductions in 3-6 months and >6 month. A similar pattern was seen in evaluation of the time course of evoked pain. As such, the benefits of long-term systemic glucocorticoid therapy may not outweigh its well-known risks, especially in patients with persistent pain. Whether this is due to non-inflammatory sources of pain or other mechanisms remains unknown and is likely heavily impacted by the specific clinical scenario.

Due to the potential long-terms side effects of chronic immunosuppression, including long-term glucocorticoid therapy in patients with persistent pain in RA, the course and predictors of unacceptable pain are of interest. Eberhard et al examined an inception cohort of RA patients in a single center in Sweden over the course of 5 years. They were found to have reduction of VAS pain from inclusion to 6 months, but pain levels largely stayed the same during the rest of the follow-up period. The proportion of patients with unacceptable pain also decreased but remained stable at about 30% after 1 year, with 20% having unacceptable pain and low inflammation and about 10% having high inflammation and unacceptable pain. The study found seropositivity, high inflammatory parameters, high DAS28 and severe patient-reported outcomes to be predictive of high inflammation and unacceptable pain and lower age, higher VAS pain, and low ESR to be predictive of low inflammation and unacceptable pain. These findings highlight the importance of examining non-inflammatory mechanisms of pain as well as identifying treatments; however, in evaluating the risk of immunosuppression and glucocorticoid therapy, it does not guide increasing or reducing treatment in RA patients with persistent pain.

Recently, ACR guidelines were published on the prevention and treatment of glucocorticoid-induced osteoporosis, emphasizing use of supplemental calcium and vitamin D and antiresorptive therapy. This randomized, controlled, open-label trial by Cho et al looks at the efficacy of selective estrogen receptor modulators (SERMs) in preventing bone loss and fractures in postmenopausal RA patients with osteopenia on long-term glucocorticoids. Patients were randomized to bazedoxefine, a 3^rd-generation SERM vs no therapy in addition to background calcium and vitamin D supplementation and bone mineral density (BMD) and trabecular bone score (TBS). Bone turnover markers were assessed over the course of 48 weeks, in addition to adverse events. Prednisone dose was relatively low, with a baseline of ~3 mg/day. Bone density increased by almost 2% in the L spine (P < 0.05), but the increases in BMD at the femoral neck and TBS were not significant. Bone turnover markers did decrease in the bazedoxefine group, though not in the control group. These findings are not striking but are promising given the short duration of the study (<1 year), and potentially deserves longer-term follow-up, both for evaluation of efficacy as well as long-term safety. In the US, the medication is only available in combination with estrogen, and thus it is not currently a practical option for RA patients with GIOP.

Despite wider availability of both synthetic and biologic DMARDs for treatment of RA in recent years, persistent pain is an issue for many patients, perhaps due to peripheral sensitization. Though it seems almost unnecessary to investigate the utility of glucocorticoids for treatment of RA-related pain, the magnitude and duration of their benefit is unknown. McWilliams et al take the approach of quantitatively analyzing the benefit of glucocorticoids in RA over time in their systematic review and meta-analysis. The study looked at both spontaneous and evoked pain, and evaluated 65 studies that mostly used pain visual analogue scale, tender joint count, and Ritchie Articular Index. Reduction in spontaneous pain was greatest in the 0-3-month time period, with smaller reductions in 3-6 months and >6 month. A similar pattern was seen in evaluation of the time course of evoked pain. As such, the benefits of long-term systemic glucocorticoid therapy may not outweigh its well-known risks, especially in patients with persistent pain. Whether this is due to non-inflammatory sources of pain or other mechanisms remains unknown and is likely heavily impacted by the specific clinical scenario.

Due to the potential long-terms side effects of chronic immunosuppression, including long-term glucocorticoid therapy in patients with persistent pain in RA, the course and predictors of unacceptable pain are of interest. Eberhard et al examined an inception cohort of RA patients in a single center in Sweden over the course of 5 years. They were found to have reduction of VAS pain from inclusion to 6 months, but pain levels largely stayed the same during the rest of the follow-up period. The proportion of patients with unacceptable pain also decreased but remained stable at about 30% after 1 year, with 20% having unacceptable pain and low inflammation and about 10% having high inflammation and unacceptable pain. The study found seropositivity, high inflammatory parameters, high DAS28 and severe patient-reported outcomes to be predictive of high inflammation and unacceptable pain and lower age, higher VAS pain, and low ESR to be predictive of low inflammation and unacceptable pain. These findings highlight the importance of examining non-inflammatory mechanisms of pain as well as identifying treatments; however, in evaluating the risk of immunosuppression and glucocorticoid therapy, it does not guide increasing or reducing treatment in RA patients with persistent pain.

Levonorgestrel intrauterine devices (LNG IUD) are a hot topic in contraceptive research. A recent study on LNG IUDs published by Fay KE et al evaluated pregnancy rates in US women who received LNG or copper IUDs for emergency contraception and reported intercourse within 7 days of insertion. Zero pregnancies were reported in women who resumed intercourse within 7 days of IUD insertion for both the LNG IUD and copper IUD, even in women who had multiple unprotected sexual encounters.  LNG IUDs are more readily accessible and better tolerated than their copper IUD counterparts, and expanding their use will only continue to improve access to reliable contraception. Women often resume penetrative intercourse shortly after initiating new contraceptive method despite counseling. Patients can be reassured that placement of a LNG IUD appears to provide immediate contraceptive benefit.

 A new estrogen is on the market for use in combined oral contraceptive pills (COC). Estetrol is a natural estrogen produced by the human fetal liver only found in circulation during pregnancy.  Estetrol was previously studied for use in menopausal hormone therapy as it acts as a mixed agonist and antagonist, offering a potential improved side effect profile with less activity in the breast and liver.  Estetrol (15 mg) was combined with 3 mg of drospirinone for a novel combined oral contraceptive option in a study by Gemzell-Danielsson K et al.  The pregnancy rate was similar to traditional COCs, demonstrating good contraceptive efficacy. Bleeding patterns and side effects were similar to traditional COCs, and one case of venous thromboembolism was reported in the large study population. A phase III trial with similar results has been completed and this new oral contraceptive formulation recently received FDA approval and is now marketed as Nextstellis. This new oral contraceptive pill hopefully represents a novel option for women who desire COCs with a low androgenic profile and VTE risk or have failed other COC formulations.  

Women are increasingly delaying childbearing, utilizing a variety of contraceptive options to avoid pregnancy. Many proactively seek to determine their fertility potential and clinicians often utilize anti-Müllerian hormone (AMH) as the standard biomarker for assessing ovarian reserve, as it is cycle independent and can be drawn at any time during a woman’s clinical assessment.  Hormonal contraception suppresses ovulation by gonadotropin suppression as a means of contraceptive action, and thus could impact an AMH value. A fascinating study by Hariton E et al looked at all contraceptive options and their impact on AMH values. AMH levels were significantly lower in women using COCs, implants, progestin-only pills, and vaginal rings compared to patients not using contraceptives, and AMH levels were slightly lower in women using hormonal IUDs. These results help clinicians counsel patients on expectations for AMH levels while on contraceptives and can guide future research to generate contraceptive-specific ranges. Women using contraceptives should be counseled to retest after stopping if AMH levels are low.

Levonorgestrel intrauterine devices (LNG IUD) are a hot topic in contraceptive research. A recent study on LNG IUDs published by Fay KE et al evaluated pregnancy rates in US women who received LNG or copper IUDs for emergency contraception and reported intercourse within 7 days of insertion. Zero pregnancies were reported in women who resumed intercourse within 7 days of IUD insertion for both the LNG IUD and copper IUD, even in women who had multiple unprotected sexual encounters.  LNG IUDs are more readily accessible and better tolerated than their copper IUD counterparts, and expanding their use will only continue to improve access to reliable contraception. Women often resume penetrative intercourse shortly after initiating new contraceptive method despite counseling. Patients can be reassured that placement of a LNG IUD appears to provide immediate contraceptive benefit.

 A new estrogen is on the market for use in combined oral contraceptive pills (COC). Estetrol is a natural estrogen produced by the human fetal liver only found in circulation during pregnancy.  Estetrol was previously studied for use in menopausal hormone therapy as it acts as a mixed agonist and antagonist, offering a potential improved side effect profile with less activity in the breast and liver.  Estetrol (15 mg) was combined with 3 mg of drospirinone for a novel combined oral contraceptive option in a study by Gemzell-Danielsson K et al.  The pregnancy rate was similar to traditional COCs, demonstrating good contraceptive efficacy. Bleeding patterns and side effects were similar to traditional COCs, and one case of venous thromboembolism was reported in the large study population. A phase III trial with similar results has been completed and this new oral contraceptive formulation recently received FDA approval and is now marketed as Nextstellis. This new oral contraceptive pill hopefully represents a novel option for women who desire COCs with a low androgenic profile and VTE risk or have failed other COC formulations.  

Women are increasingly delaying childbearing, utilizing a variety of contraceptive options to avoid pregnancy. Many proactively seek to determine their fertility potential and clinicians often utilize anti-Müllerian hormone (AMH) as the standard biomarker for assessing ovarian reserve, as it is cycle independent and can be drawn at any time during a woman’s clinical assessment.  Hormonal contraception suppresses ovulation by gonadotropin suppression as a means of contraceptive action, and thus could impact an AMH value. A fascinating study by Hariton E et al looked at all contraceptive options and their impact on AMH values. AMH levels were significantly lower in women using COCs, implants, progestin-only pills, and vaginal rings compared to patients not using contraceptives, and AMH levels were slightly lower in women using hormonal IUDs. These results help clinicians counsel patients on expectations for AMH levels while on contraceptives and can guide future research to generate contraceptive-specific ranges. Women using contraceptives should be counseled to retest after stopping if AMH levels are low.

Levonorgestrel intrauterine devices (LNG IUD) are a hot topic in contraceptive research. A recent study on LNG IUDs published by Fay KE et al evaluated pregnancy rates in US women who received LNG or copper IUDs for emergency contraception and reported intercourse within 7 days of insertion. Zero pregnancies were reported in women who resumed intercourse within 7 days of IUD insertion for both the LNG IUD and copper IUD, even in women who had multiple unprotected sexual encounters.  LNG IUDs are more readily accessible and better tolerated than their copper IUD counterparts, and expanding their use will only continue to improve access to reliable contraception. Women often resume penetrative intercourse shortly after initiating new contraceptive method despite counseling. Patients can be reassured that placement of a LNG IUD appears to provide immediate contraceptive benefit.

 A new estrogen is on the market for use in combined oral contraceptive pills (COC). Estetrol is a natural estrogen produced by the human fetal liver only found in circulation during pregnancy.  Estetrol was previously studied for use in menopausal hormone therapy as it acts as a mixed agonist and antagonist, offering a potential improved side effect profile with less activity in the breast and liver.  Estetrol (15 mg) was combined with 3 mg of drospirinone for a novel combined oral contraceptive option in a study by Gemzell-Danielsson K et al.  The pregnancy rate was similar to traditional COCs, demonstrating good contraceptive efficacy. Bleeding patterns and side effects were similar to traditional COCs, and one case of venous thromboembolism was reported in the large study population. A phase III trial with similar results has been completed and this new oral contraceptive formulation recently received FDA approval and is now marketed as Nextstellis. This new oral contraceptive pill hopefully represents a novel option for women who desire COCs with a low androgenic profile and VTE risk or have failed other COC formulations.  

Women are increasingly delaying childbearing, utilizing a variety of contraceptive options to avoid pregnancy. Many proactively seek to determine their fertility potential and clinicians often utilize anti-Müllerian hormone (AMH) as the standard biomarker for assessing ovarian reserve, as it is cycle independent and can be drawn at any time during a woman’s clinical assessment.  Hormonal contraception suppresses ovulation by gonadotropin suppression as a means of contraceptive action, and thus could impact an AMH value. A fascinating study by Hariton E et al looked at all contraceptive options and their impact on AMH values. AMH levels were significantly lower in women using COCs, implants, progestin-only pills, and vaginal rings compared to patients not using contraceptives, and AMH levels were slightly lower in women using hormonal IUDs. These results help clinicians counsel patients on expectations for AMH levels while on contraceptives and can guide future research to generate contraceptive-specific ranges. Women using contraceptives should be counseled to retest after stopping if AMH levels are low.

In most patients with psoriatic arthritis (PsA), the musculoskeletal manifestations occur after the onset of cutaneous manifestations. The mechanisms underlying the triggering of joint disease is still not well understood, one burning question is whether early and effective treatment of cutaneous psoriasis will reduce the incidence of PsA. In a retrospective non-randomised study, Gisondi et al compared the incidence rates of PsA in patients with chronic plaque psoriasis receiving either continuous treatment with a biologic disease modifying anti-rheumatic drugs (bDMARD- infliximab, etanercept, adalimumab, ustekinumab and secukinumab) for at least 5 years (n=234, 1584 person-year of follow-up) or at least three courses of narrow band ultraviolet B (nb-UVB) phototherapy (n=230, 1478 person-year of follow-up). bDMARDs treatment was associated with a lower risk of incident PsA (adjusted hazard ratio 0.27, 95% Confidence Interval 0.11–0.66). However, analysis after propensity score matching found no significant difference between treatment with bDMARDs and nb-UVB phototherapy and the risk of incident PsA. Prospective studies are required to answer this important question. Interestingly, nail psoriasis was associated with higher risk of PsA, confirming previous observations.

Due to lack of disease activity biomarkers clinical assessment of disease activity in PsA patients with concomitant fibromyalgia can be challenging. Ultrasound (US) may however be useful in providing objective assessment of disease activity. Polachek et al compared 42 patients with PsA and coexisting fibromyalgia syndrome (FMS) (satisfying CASPAR criteria and the 2016 fibromyalgia classification criteria) to 114 PsA patients without FMS (satisfying CASPAR criteria alone). All patients underwent detailed US evaluation including 52 joints, 40 tendons and 14 entheses, and a scores for synovitis, tenosynovitis and enthesitis were summed to obtain a final US disease activity score for each patient. Those with FMS had higher scores of composite clinical disease activity indices. However, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with composite indices in PsA patients without FMS but not in PsA patients with FMS. Thus, US is a tool that can be employed to determine PsA disease activity in patients with concomitant FMS. However, the scanning protocol as described is time consuming. A shortened protocol as well as training of rheumatologists and radiologists for reliably assessing synovitis, tenosynovitis and enthesitis is required before US can be feasibly and reliably used in clinical practice.

IL-23 inhibitors were not found to be efficacious in the treatment of axial spondyloarthritis. It is not clear whether these inhibitors improve axial disease in PsA patients, and if indeed axial PsA is distinct from primary axial spondyloarthritis. In a post-hoc analyses of the DISCOVER 1 and DISCOVER 2 studies that included 312 patients with PsA with imaging-confirmed sacroiliitis randomly assigned to either placebo (n=118), guselkumab Q4 (n=103), or Q8 (n=91), Mease et al demonstrated that at week 24, guselkumab Q4 and Q8 groups vs placebo showed higher least-squares mean changes in BASDAI (−2.7 and −2.7 vs −1.3; P less than .0001) and ASDAS (−1.4 and −1.4 vs −0.7; P less than .0001) scores, which were maintained until week 52. Thus, Guselkumab may improve axial PsA. However, axial PsA has not yet been formally defined, and BASDAI and ASDAS are not specific for axial PsA. Once axial PsA is defined, prospective randomised clinical trials with associated MRI studies will be required to determine if IL-23 inhibitors improve symptoms of axial PsA.

In most patients with psoriatic arthritis (PsA), the musculoskeletal manifestations occur after the onset of cutaneous manifestations. The mechanisms underlying the triggering of joint disease is still not well understood, one burning question is whether early and effective treatment of cutaneous psoriasis will reduce the incidence of PsA. In a retrospective non-randomised study, Gisondi et al compared the incidence rates of PsA in patients with chronic plaque psoriasis receiving either continuous treatment with a biologic disease modifying anti-rheumatic drugs (bDMARD- infliximab, etanercept, adalimumab, ustekinumab and secukinumab) for at least 5 years (n=234, 1584 person-year of follow-up) or at least three courses of narrow band ultraviolet B (nb-UVB) phototherapy (n=230, 1478 person-year of follow-up). bDMARDs treatment was associated with a lower risk of incident PsA (adjusted hazard ratio 0.27, 95% Confidence Interval 0.11–0.66). However, analysis after propensity score matching found no significant difference between treatment with bDMARDs and nb-UVB phototherapy and the risk of incident PsA. Prospective studies are required to answer this important question. Interestingly, nail psoriasis was associated with higher risk of PsA, confirming previous observations.

Due to lack of disease activity biomarkers clinical assessment of disease activity in PsA patients with concomitant fibromyalgia can be challenging. Ultrasound (US) may however be useful in providing objective assessment of disease activity. Polachek et al compared 42 patients with PsA and coexisting fibromyalgia syndrome (FMS) (satisfying CASPAR criteria and the 2016 fibromyalgia classification criteria) to 114 PsA patients without FMS (satisfying CASPAR criteria alone). All patients underwent detailed US evaluation including 52 joints, 40 tendons and 14 entheses, and a scores for synovitis, tenosynovitis and enthesitis were summed to obtain a final US disease activity score for each patient. Those with FMS had higher scores of composite clinical disease activity indices. However, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with composite indices in PsA patients without FMS but not in PsA patients with FMS. Thus, US is a tool that can be employed to determine PsA disease activity in patients with concomitant FMS. However, the scanning protocol as described is time consuming. A shortened protocol as well as training of rheumatologists and radiologists for reliably assessing synovitis, tenosynovitis and enthesitis is required before US can be feasibly and reliably used in clinical practice.

IL-23 inhibitors were not found to be efficacious in the treatment of axial spondyloarthritis. It is not clear whether these inhibitors improve axial disease in PsA patients, and if indeed axial PsA is distinct from primary axial spondyloarthritis. In a post-hoc analyses of the DISCOVER 1 and DISCOVER 2 studies that included 312 patients with PsA with imaging-confirmed sacroiliitis randomly assigned to either placebo (n=118), guselkumab Q4 (n=103), or Q8 (n=91), Mease et al demonstrated that at week 24, guselkumab Q4 and Q8 groups vs placebo showed higher least-squares mean changes in BASDAI (−2.7 and −2.7 vs −1.3; P less than .0001) and ASDAS (−1.4 and −1.4 vs −0.7; P less than .0001) scores, which were maintained until week 52. Thus, Guselkumab may improve axial PsA. However, axial PsA has not yet been formally defined, and BASDAI and ASDAS are not specific for axial PsA. Once axial PsA is defined, prospective randomised clinical trials with associated MRI studies will be required to determine if IL-23 inhibitors improve symptoms of axial PsA.

In most patients with psoriatic arthritis (PsA), the musculoskeletal manifestations occur after the onset of cutaneous manifestations. The mechanisms underlying the triggering of joint disease is still not well understood, one burning question is whether early and effective treatment of cutaneous psoriasis will reduce the incidence of PsA. In a retrospective non-randomised study, Gisondi et al compared the incidence rates of PsA in patients with chronic plaque psoriasis receiving either continuous treatment with a biologic disease modifying anti-rheumatic drugs (bDMARD- infliximab, etanercept, adalimumab, ustekinumab and secukinumab) for at least 5 years (n=234, 1584 person-year of follow-up) or at least three courses of narrow band ultraviolet B (nb-UVB) phototherapy (n=230, 1478 person-year of follow-up). bDMARDs treatment was associated with a lower risk of incident PsA (adjusted hazard ratio 0.27, 95% Confidence Interval 0.11–0.66). However, analysis after propensity score matching found no significant difference between treatment with bDMARDs and nb-UVB phototherapy and the risk of incident PsA. Prospective studies are required to answer this important question. Interestingly, nail psoriasis was associated with higher risk of PsA, confirming previous observations.

Due to lack of disease activity biomarkers clinical assessment of disease activity in PsA patients with concomitant fibromyalgia can be challenging. Ultrasound (US) may however be useful in providing objective assessment of disease activity. Polachek et al compared 42 patients with PsA and coexisting fibromyalgia syndrome (FMS) (satisfying CASPAR criteria and the 2016 fibromyalgia classification criteria) to 114 PsA patients without FMS (satisfying CASPAR criteria alone). All patients underwent detailed US evaluation including 52 joints, 40 tendons and 14 entheses, and a scores for synovitis, tenosynovitis and enthesitis were summed to obtain a final US disease activity score for each patient. Those with FMS had higher scores of composite clinical disease activity indices. However, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with composite indices in PsA patients without FMS but not in PsA patients with FMS. Thus, US is a tool that can be employed to determine PsA disease activity in patients with concomitant FMS. However, the scanning protocol as described is time consuming. A shortened protocol as well as training of rheumatologists and radiologists for reliably assessing synovitis, tenosynovitis and enthesitis is required before US can be feasibly and reliably used in clinical practice.

IL-23 inhibitors were not found to be efficacious in the treatment of axial spondyloarthritis. It is not clear whether these inhibitors improve axial disease in PsA patients, and if indeed axial PsA is distinct from primary axial spondyloarthritis. In a post-hoc analyses of the DISCOVER 1 and DISCOVER 2 studies that included 312 patients with PsA with imaging-confirmed sacroiliitis randomly assigned to either placebo (n=118), guselkumab Q4 (n=103), or Q8 (n=91), Mease et al demonstrated that at week 24, guselkumab Q4 and Q8 groups vs placebo showed higher least-squares mean changes in BASDAI (−2.7 and −2.7 vs −1.3; P less than .0001) and ASDAS (−1.4 and −1.4 vs −0.7; P less than .0001) scores, which were maintained until week 52. Thus, Guselkumab may improve axial PsA. However, axial PsA has not yet been formally defined, and BASDAI and ASDAS are not specific for axial PsA. Once axial PsA is defined, prospective randomised clinical trials with associated MRI studies will be required to determine if IL-23 inhibitors improve symptoms of axial PsA.

For patients with hepatocellular carcinoma (HCC) and liver-dominant disease, liver-directed therapy is frequently used as the initial attempt to control this malignancy. This month we will review several journal articles that address different forms of localized HCC management.

Ding W et al. analyzed 401 patients with early HCC who were treated in one center, either with microwave ablation (MWA, n=240) or robotic-assisted hepatectomy (RH, n=161). Following propensity-score matching (PSM) and inverse probability of treatment weight analysis, the authors found that both treatments can achieve safe, comparable therapeutic effects. The 3-year recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) of MWA group and RH group were 52.2% vs 65.8%, 91.5% vs 91.3% and 91.5% vs 91.3%, respectively. OS and CSS were comparable (P = 0.44 and 0.96), while RFS of patients treated with MWA was slightly lower but not significantly so (P = 0.097). The authors concluded that both minimally-invasive approaches are effective in the treatment of early HCC. MWA was less invasive, while RH had better accuracy and caused less damage to the liver parenchyma.

Transarterial therapies are frequently withheld in patients who have major vascular invasion (HCC-MVI), and patients usually receive palliative systemic therapy instead. Kwee et al. examined the National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between transarterial radioembolization (TARE) and systemic therapy in hepatocellular carcinoma (HCC) with major vascular invasion (HCC-MVI). OS was compared by propensity-score matched Cox regression and landmark analysis in 1514 patients with HCC-MVI who were treated between 2010 and 2015. Propensity-score matched and landmark-time adjusted analysis associated TARE with a median OS 7.1 months (95% CI 5.0 to 10.5) vs 4.9 months (95% CI 3.9 to 6.5) for patients treated with systemic therapy only, HR 0.74 (95% CI 0.60 to 0.91, P = 0.005). The authors were encouraged by these results, and suggested that additional prospective studies using TARE as treatment of HCC-MVI should be undertaken.

The SARAH trial (Vilgrain et al., Lancet Oncology 2017) compared the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres (also termed TARE, transarterial radioembolization) in patients with hepatocellular carcinoma. The final conclusion was that overall survival did not significantly differ between the two groups. Pereira et al. published this ancillary study of the SARAH trial that compares health-related quality of life (HRQoL) between the two groups. HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) in the TARE group, vs 2.6 months (95% CI 2.0–3.0) in the sorafenib group. The authors concluded that the differences in HRQoL should inform decisions when recommending initial treatment of patients with HCC, though it does not take into account recently developed advancements in systemic therapy including immunotherapy.

For patients with hepatocellular carcinoma (HCC) and liver-dominant disease, liver-directed therapy is frequently used as the initial attempt to control this malignancy. This month we will review several journal articles that address different forms of localized HCC management.

Ding W et al. analyzed 401 patients with early HCC who were treated in one center, either with microwave ablation (MWA, n=240) or robotic-assisted hepatectomy (RH, n=161). Following propensity-score matching (PSM) and inverse probability of treatment weight analysis, the authors found that both treatments can achieve safe, comparable therapeutic effects. The 3-year recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) of MWA group and RH group were 52.2% vs 65.8%, 91.5% vs 91.3% and 91.5% vs 91.3%, respectively. OS and CSS were comparable (P = 0.44 and 0.96), while RFS of patients treated with MWA was slightly lower but not significantly so (P = 0.097). The authors concluded that both minimally-invasive approaches are effective in the treatment of early HCC. MWA was less invasive, while RH had better accuracy and caused less damage to the liver parenchyma.

Transarterial therapies are frequently withheld in patients who have major vascular invasion (HCC-MVI), and patients usually receive palliative systemic therapy instead. Kwee et al. examined the National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between transarterial radioembolization (TARE) and systemic therapy in hepatocellular carcinoma (HCC) with major vascular invasion (HCC-MVI). OS was compared by propensity-score matched Cox regression and landmark analysis in 1514 patients with HCC-MVI who were treated between 2010 and 2015. Propensity-score matched and landmark-time adjusted analysis associated TARE with a median OS 7.1 months (95% CI 5.0 to 10.5) vs 4.9 months (95% CI 3.9 to 6.5) for patients treated with systemic therapy only, HR 0.74 (95% CI 0.60 to 0.91, P = 0.005). The authors were encouraged by these results, and suggested that additional prospective studies using TARE as treatment of HCC-MVI should be undertaken.

The SARAH trial (Vilgrain et al., Lancet Oncology 2017) compared the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres (also termed TARE, transarterial radioembolization) in patients with hepatocellular carcinoma. The final conclusion was that overall survival did not significantly differ between the two groups. Pereira et al. published this ancillary study of the SARAH trial that compares health-related quality of life (HRQoL) between the two groups. HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) in the TARE group, vs 2.6 months (95% CI 2.0–3.0) in the sorafenib group. The authors concluded that the differences in HRQoL should inform decisions when recommending initial treatment of patients with HCC, though it does not take into account recently developed advancements in systemic therapy including immunotherapy.

For patients with hepatocellular carcinoma (HCC) and liver-dominant disease, liver-directed therapy is frequently used as the initial attempt to control this malignancy. This month we will review several journal articles that address different forms of localized HCC management.

Ding W et al. analyzed 401 patients with early HCC who were treated in one center, either with microwave ablation (MWA, n=240) or robotic-assisted hepatectomy (RH, n=161). Following propensity-score matching (PSM) and inverse probability of treatment weight analysis, the authors found that both treatments can achieve safe, comparable therapeutic effects. The 3-year recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) of MWA group and RH group were 52.2% vs 65.8%, 91.5% vs 91.3% and 91.5% vs 91.3%, respectively. OS and CSS were comparable (P = 0.44 and 0.96), while RFS of patients treated with MWA was slightly lower but not significantly so (P = 0.097). The authors concluded that both minimally-invasive approaches are effective in the treatment of early HCC. MWA was less invasive, while RH had better accuracy and caused less damage to the liver parenchyma.

Transarterial therapies are frequently withheld in patients who have major vascular invasion (HCC-MVI), and patients usually receive palliative systemic therapy instead. Kwee et al. examined the National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between transarterial radioembolization (TARE) and systemic therapy in hepatocellular carcinoma (HCC) with major vascular invasion (HCC-MVI). OS was compared by propensity-score matched Cox regression and landmark analysis in 1514 patients with HCC-MVI who were treated between 2010 and 2015. Propensity-score matched and landmark-time adjusted analysis associated TARE with a median OS 7.1 months (95% CI 5.0 to 10.5) vs 4.9 months (95% CI 3.9 to 6.5) for patients treated with systemic therapy only, HR 0.74 (95% CI 0.60 to 0.91, P = 0.005). The authors were encouraged by these results, and suggested that additional prospective studies using TARE as treatment of HCC-MVI should be undertaken.

The SARAH trial (Vilgrain et al., Lancet Oncology 2017) compared the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres (also termed TARE, transarterial radioembolization) in patients with hepatocellular carcinoma. The final conclusion was that overall survival did not significantly differ between the two groups. Pereira et al. published this ancillary study of the SARAH trial that compares health-related quality of life (HRQoL) between the two groups. HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) in the TARE group, vs 2.6 months (95% CI 2.0–3.0) in the sorafenib group. The authors concluded that the differences in HRQoL should inform decisions when recommending initial treatment of patients with HCC, though it does not take into account recently developed advancements in systemic therapy including immunotherapy.

The efficacy of vaccination against SARS-CoV-2 in patients with IBD and complications from a COVID-19 infection unique to patients with IBD have not been well elucidated. This month, three manuscripts were published in Gastroenterology examining real-world data on vaccine efficacy and COVID infection outcomes in IBD patients.

Over 60% of Israelis have been fully vaccinated.  Ben-Tov and colleagues evaluated the efficacy of BNT162b2 vaccination in 12,231 IBD patients matched to 36,254 using data from the second largest state-mandated healthcare provider in Israel. Seven days after the second vaccination, breakthrough infections were observed in 0.19% of IBD patients and 0.15% of control patients.  Of the 23 breakthrough infections in IBD patients, 2 patients were hospitalized, and one patient died.  Crohn’s disease patients were at greater risk of breakthrough infections in a multivariable analysis [HR3.56 (95% CI-1.29,9.83). Patients with UC and those on immune modifying agents did not have a higher risk of breakthrough infections. It should be noted that that these results may not be generalizable to other populations, as the median age was 47 and there were limited patients on immunosuppressive therapies (10.8% on anti-TNF, 1.4% on methotrexate, 4.8% on thiopurines).

A similar study by Hadi et al.  retrospectively examined the safety and efficacy of vaccination in IBD patients using a large United States research network encompassing >800,000 vaccinated patients. Of these patients, 5,562 had a diagnosis of IBD (3,740 received both vaccine doses). In contrast to the previous study, 53% of patients were on a biologic and/or thiopurine. In this analysis, there were no differences in the rate of adverse events reported, subsequent COVID-19 infections, or COVID-19 related hospitalizations between IBD and non-IBD patients. In addition, there was not a higher rate of adverse events after vaccination between those on a biologic or immunomodulator compared. The authors state that there were ≤10 breakthrough infections in patients on a biologic or immunomodulator, although did not perform a statistical comparison to IBD patients not on immunosuppressive therapies.

These manuscripts evaluated outcomes in large cohorts of IBD patients, although the results are limited by the fact that they relied on diagnosis coding for inclusion of IBD patients and recording of events. Furthermore, it is likely that many patients with SARS-CoV-2 infections are diagnosed outside an individuals’ healthcare system limiting capturing of events for their analyses. Nevertheless, these studies clearly demonstrate safety and efficacy of COVID-19 vaccination in patients with IBD. Further work is needed, however, to evaluate real-world long-term efficacy of vaccination in IBD patients on immunosuppressive therapy.

Both IBD and SARS-CoV-2 increase an individual’s risk of a venous thromboembolism (VTE). Using a veteran’s administrations (VA) cohort, Mahmud and colleagues identified 428 patients with IBD who developed a VTE within the one year study period. After adjusting for recent hospitalizations and steroid exposure, SARS-CoV-2 infection was associated with an 8.15-fold increased risk of VTE (95% CI 4.34-15.30). This study is limited by the fact that there were just 21 events of VTE after a SARS-CoV-2 infection. If the results are validated in an independent larger cohort of patients, however, practitioners should consider VTE prophylaxis in IBD patients with a SARS-CoV-2 infection.

The efficacy of vaccination against SARS-CoV-2 in patients with IBD and complications from a COVID-19 infection unique to patients with IBD have not been well elucidated. This month, three manuscripts were published in Gastroenterology examining real-world data on vaccine efficacy and COVID infection outcomes in IBD patients.

Over 60% of Israelis have been fully vaccinated.  Ben-Tov and colleagues evaluated the efficacy of BNT162b2 vaccination in 12,231 IBD patients matched to 36,254 using data from the second largest state-mandated healthcare provider in Israel. Seven days after the second vaccination, breakthrough infections were observed in 0.19% of IBD patients and 0.15% of control patients.  Of the 23 breakthrough infections in IBD patients, 2 patients were hospitalized, and one patient died.  Crohn’s disease patients were at greater risk of breakthrough infections in a multivariable analysis [HR3.56 (95% CI-1.29,9.83). Patients with UC and those on immune modifying agents did not have a higher risk of breakthrough infections. It should be noted that that these results may not be generalizable to other populations, as the median age was 47 and there were limited patients on immunosuppressive therapies (10.8% on anti-TNF, 1.4% on methotrexate, 4.8% on thiopurines).

A similar study by Hadi et al.  retrospectively examined the safety and efficacy of vaccination in IBD patients using a large United States research network encompassing >800,000 vaccinated patients. Of these patients, 5,562 had a diagnosis of IBD (3,740 received both vaccine doses). In contrast to the previous study, 53% of patients were on a biologic and/or thiopurine. In this analysis, there were no differences in the rate of adverse events reported, subsequent COVID-19 infections, or COVID-19 related hospitalizations between IBD and non-IBD patients. In addition, there was not a higher rate of adverse events after vaccination between those on a biologic or immunomodulator compared. The authors state that there were ≤10 breakthrough infections in patients on a biologic or immunomodulator, although did not perform a statistical comparison to IBD patients not on immunosuppressive therapies.

These manuscripts evaluated outcomes in large cohorts of IBD patients, although the results are limited by the fact that they relied on diagnosis coding for inclusion of IBD patients and recording of events. Furthermore, it is likely that many patients with SARS-CoV-2 infections are diagnosed outside an individuals’ healthcare system limiting capturing of events for their analyses. Nevertheless, these studies clearly demonstrate safety and efficacy of COVID-19 vaccination in patients with IBD. Further work is needed, however, to evaluate real-world long-term efficacy of vaccination in IBD patients on immunosuppressive therapy.

Both IBD and SARS-CoV-2 increase an individual’s risk of a venous thromboembolism (VTE). Using a veteran’s administrations (VA) cohort, Mahmud and colleagues identified 428 patients with IBD who developed a VTE within the one year study period. After adjusting for recent hospitalizations and steroid exposure, SARS-CoV-2 infection was associated with an 8.15-fold increased risk of VTE (95% CI 4.34-15.30). This study is limited by the fact that there were just 21 events of VTE after a SARS-CoV-2 infection. If the results are validated in an independent larger cohort of patients, however, practitioners should consider VTE prophylaxis in IBD patients with a SARS-CoV-2 infection.

The efficacy of vaccination against SARS-CoV-2 in patients with IBD and complications from a COVID-19 infection unique to patients with IBD have not been well elucidated. This month, three manuscripts were published in Gastroenterology examining real-world data on vaccine efficacy and COVID infection outcomes in IBD patients.

Over 60% of Israelis have been fully vaccinated.  Ben-Tov and colleagues evaluated the efficacy of BNT162b2 vaccination in 12,231 IBD patients matched to 36,254 using data from the second largest state-mandated healthcare provider in Israel. Seven days after the second vaccination, breakthrough infections were observed in 0.19% of IBD patients and 0.15% of control patients.  Of the 23 breakthrough infections in IBD patients, 2 patients were hospitalized, and one patient died.  Crohn’s disease patients were at greater risk of breakthrough infections in a multivariable analysis [HR3.56 (95% CI-1.29,9.83). Patients with UC and those on immune modifying agents did not have a higher risk of breakthrough infections. It should be noted that that these results may not be generalizable to other populations, as the median age was 47 and there were limited patients on immunosuppressive therapies (10.8% on anti-TNF, 1.4% on methotrexate, 4.8% on thiopurines).

A similar study by Hadi et al.  retrospectively examined the safety and efficacy of vaccination in IBD patients using a large United States research network encompassing >800,000 vaccinated patients. Of these patients, 5,562 had a diagnosis of IBD (3,740 received both vaccine doses). In contrast to the previous study, 53% of patients were on a biologic and/or thiopurine. In this analysis, there were no differences in the rate of adverse events reported, subsequent COVID-19 infections, or COVID-19 related hospitalizations between IBD and non-IBD patients. In addition, there was not a higher rate of adverse events after vaccination between those on a biologic or immunomodulator compared. The authors state that there were ≤10 breakthrough infections in patients on a biologic or immunomodulator, although did not perform a statistical comparison to IBD patients not on immunosuppressive therapies.

These manuscripts evaluated outcomes in large cohorts of IBD patients, although the results are limited by the fact that they relied on diagnosis coding for inclusion of IBD patients and recording of events. Furthermore, it is likely that many patients with SARS-CoV-2 infections are diagnosed outside an individuals’ healthcare system limiting capturing of events for their analyses. Nevertheless, these studies clearly demonstrate safety and efficacy of COVID-19 vaccination in patients with IBD. Further work is needed, however, to evaluate real-world long-term efficacy of vaccination in IBD patients on immunosuppressive therapy.

Both IBD and SARS-CoV-2 increase an individual’s risk of a venous thromboembolism (VTE). Using a veteran’s administrations (VA) cohort, Mahmud and colleagues identified 428 patients with IBD who developed a VTE within the one year study period. After adjusting for recent hospitalizations and steroid exposure, SARS-CoV-2 infection was associated with an 8.15-fold increased risk of VTE (95% CI 4.34-15.30). This study is limited by the fact that there were just 21 events of VTE after a SARS-CoV-2 infection. If the results are validated in an independent larger cohort of patients, however, practitioners should consider VTE prophylaxis in IBD patients with a SARS-CoV-2 infection.

Several recent studies have evaluated risks of therapy in rheumatoid arthritis (RA). One question regarding treatment of early RA is whether different initial treatment strategies confer different risks. In a systematic review with network meta-analysis, Adas et al reviewed differences between methotrexate, biologic disease-modifying antirheumatic drug (bDMARD), and steroid use in early RA. Overall, risk of serious adverse events was higher with bDMARD monotherapy than methotrexate monotherapy. Of note, while generally long-term steroid use is disfavored due to adverse effects, serious adverse events were not increased in patients treated with methotrexate and steroids together. The size of differences in risk was small and study heterogeneity, including the class of bDMARDs, limits generalizability of this information; thus, variations in the studies themselves may account for these differences.

Pazmino et al also looked at treatment strategies in early RA in a post hoc analysis of participants at “low-risk” for poor prognosis in the CareRA trial, in which patients were randomized to step-up methotrexate without glucocorticoids or step-down with glucocorticoids. While pain scores and disease activity scores were similar among the two groups, analgesic use (including non-steroidal anti-inflammatory drugs [NSAIDs] and opioids) was significantly lower among those randomized to the glucocorticoid-bridging arm. Though this information is reassuring as to the utility of glucocorticoids, it is not clear that this correlation is broadly applicable, for example, among the “higher-risk” patients who might otherwise be more likely to receive glucocorticoids.

A recent analysis of the COVID-19 global rheumatology alliance physician registry by Sparks et al of cases of COVID-19 in patients with rheumatic disease looked more specifically at COVID-19 outcomes in patients with RA on biologic therapy. These are of interest due both to the risk of immunosuppression overall as well as the use of immunosuppressive medications in COVID-19-associated hyperinflammation. The study evaluated outcomes of hospitalization (including respiratory support and mortality). While hospitalization is difficult to evaluate as an outcome without knowing the background rate of COVID in the different areas, of the hospitalized patients, patients who used Janus kinase inhibitors (JAKi) and rituximab received oxygen or ventilator support and had higher mortality than those who were on abatacept, IL-6 inhibitors, or TNF inhibitors. Wider interpretation is difficult due to lack of knowledge of when medications were given (including rituximab dosing), but the results suggest that concern is warranted in improving outcomes for patients with RA on these therapies.

Finally, regarding the well-known cardiovascular risk associated with RA, several observational studies have suggested that methotrexate is associated with reduction in risk of cardiovascular events. This cohort study of the Veterans Affairs RA registry followed over 2000 patients for a mean of about 5 years; a reduction in incidence of cardiovascular events was associated with methotrexate use, independent of age, body mass index (BMI), cardiovascular risk factors, RA disease activity, and other RA therapies. It may be that methotrexate use is associated with an unknown mediator of cardiovascular disease not evaluated in this study, such as reduced glucocorticoid or NSAID use, but this area deserves further investigation.

Several recent studies have evaluated risks of therapy in rheumatoid arthritis (RA). One question regarding treatment of early RA is whether different initial treatment strategies confer different risks. In a systematic review with network meta-analysis, Adas et al reviewed differences between methotrexate, biologic disease-modifying antirheumatic drug (bDMARD), and steroid use in early RA. Overall, risk of serious adverse events was higher with bDMARD monotherapy than methotrexate monotherapy. Of note, while generally long-term steroid use is disfavored due to adverse effects, serious adverse events were not increased in patients treated with methotrexate and steroids together. The size of differences in risk was small and study heterogeneity, including the class of bDMARDs, limits generalizability of this information; thus, variations in the studies themselves may account for these differences.

Pazmino et al also looked at treatment strategies in early RA in a post hoc analysis of participants at “low-risk” for poor prognosis in the CareRA trial, in which patients were randomized to step-up methotrexate without glucocorticoids or step-down with glucocorticoids. While pain scores and disease activity scores were similar among the two groups, analgesic use (including non-steroidal anti-inflammatory drugs [NSAIDs] and opioids) was significantly lower among those randomized to the glucocorticoid-bridging arm. Though this information is reassuring as to the utility of glucocorticoids, it is not clear that this correlation is broadly applicable, for example, among the “higher-risk” patients who might otherwise be more likely to receive glucocorticoids.

A recent analysis of the COVID-19 global rheumatology alliance physician registry by Sparks et al of cases of COVID-19 in patients with rheumatic disease looked more specifically at COVID-19 outcomes in patients with RA on biologic therapy. These are of interest due both to the risk of immunosuppression overall as well as the use of immunosuppressive medications in COVID-19-associated hyperinflammation. The study evaluated outcomes of hospitalization (including respiratory support and mortality). While hospitalization is difficult to evaluate as an outcome without knowing the background rate of COVID in the different areas, of the hospitalized patients, patients who used Janus kinase inhibitors (JAKi) and rituximab received oxygen or ventilator support and had higher mortality than those who were on abatacept, IL-6 inhibitors, or TNF inhibitors. Wider interpretation is difficult due to lack of knowledge of when medications were given (including rituximab dosing), but the results suggest that concern is warranted in improving outcomes for patients with RA on these therapies.

Finally, regarding the well-known cardiovascular risk associated with RA, several observational studies have suggested that methotrexate is associated with reduction in risk of cardiovascular events. This cohort study of the Veterans Affairs RA registry followed over 2000 patients for a mean of about 5 years; a reduction in incidence of cardiovascular events was associated with methotrexate use, independent of age, body mass index (BMI), cardiovascular risk factors, RA disease activity, and other RA therapies. It may be that methotrexate use is associated with an unknown mediator of cardiovascular disease not evaluated in this study, such as reduced glucocorticoid or NSAID use, but this area deserves further investigation.

Several recent studies have evaluated risks of therapy in rheumatoid arthritis (RA). One question regarding treatment of early RA is whether different initial treatment strategies confer different risks. In a systematic review with network meta-analysis, Adas et al reviewed differences between methotrexate, biologic disease-modifying antirheumatic drug (bDMARD), and steroid use in early RA. Overall, risk of serious adverse events was higher with bDMARD monotherapy than methotrexate monotherapy. Of note, while generally long-term steroid use is disfavored due to adverse effects, serious adverse events were not increased in patients treated with methotrexate and steroids together. The size of differences in risk was small and study heterogeneity, including the class of bDMARDs, limits generalizability of this information; thus, variations in the studies themselves may account for these differences.

Pazmino et al also looked at treatment strategies in early RA in a post hoc analysis of participants at “low-risk” for poor prognosis in the CareRA trial, in which patients were randomized to step-up methotrexate without glucocorticoids or step-down with glucocorticoids. While pain scores and disease activity scores were similar among the two groups, analgesic use (including non-steroidal anti-inflammatory drugs [NSAIDs] and opioids) was significantly lower among those randomized to the glucocorticoid-bridging arm. Though this information is reassuring as to the utility of glucocorticoids, it is not clear that this correlation is broadly applicable, for example, among the “higher-risk” patients who might otherwise be more likely to receive glucocorticoids.

A recent analysis of the COVID-19 global rheumatology alliance physician registry by Sparks et al of cases of COVID-19 in patients with rheumatic disease looked more specifically at COVID-19 outcomes in patients with RA on biologic therapy. These are of interest due both to the risk of immunosuppression overall as well as the use of immunosuppressive medications in COVID-19-associated hyperinflammation. The study evaluated outcomes of hospitalization (including respiratory support and mortality). While hospitalization is difficult to evaluate as an outcome without knowing the background rate of COVID in the different areas, of the hospitalized patients, patients who used Janus kinase inhibitors (JAKi) and rituximab received oxygen or ventilator support and had higher mortality than those who were on abatacept, IL-6 inhibitors, or TNF inhibitors. Wider interpretation is difficult due to lack of knowledge of when medications were given (including rituximab dosing), but the results suggest that concern is warranted in improving outcomes for patients with RA on these therapies.

Finally, regarding the well-known cardiovascular risk associated with RA, several observational studies have suggested that methotrexate is associated with reduction in risk of cardiovascular events. This cohort study of the Veterans Affairs RA registry followed over 2000 patients for a mean of about 5 years; a reduction in incidence of cardiovascular events was associated with methotrexate use, independent of age, body mass index (BMI), cardiovascular risk factors, RA disease activity, and other RA therapies. It may be that methotrexate use is associated with an unknown mediator of cardiovascular disease not evaluated in this study, such as reduced glucocorticoid or NSAID use, but this area deserves further investigation.

Janus kinase inhibitors (JAK inhibitors) have demonstrated efficacy in several immune mediated inflammatory conditions. Tofacitinib, which inhibits JAK3 and JAK1 greater than JAK2, was the first JAK inhibitor approved by the FDA for ulcerative colitis. In contrast to tofacitinib, filgotinib, preferentially inhibits JAK1. The efficacy of filgotinib during induction and maintenance therapy in ulcerative colitis was studied in a phase 2b/3 randomized control trial, the SELECTION trial. In this trial, 659 biologic-naïve and 689 biologic-experienced patients with moderate to severely active ulcerative colitis were randomized 2:2:1 to receive filgotinib 200mg daily, filgotinib 100mg daily, or placebo for 11 weeks. Responders to treatment with filgotinib at week 10 were rerandomized to their original dose or placebo in a 2:1 manner for a total treatment course of 58 weeks. The primary endpoint of the study was clinical remission which was defined as a Mayo endoscopy subscore of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency from baseline for a subscore of 0 or 1.

In biologic naïve patients, 26.1% of patients treated with filgotinib 200mg (P = .016) and 19.1% treated with filgotinib 100mg (P = 0.34) compared to 15.3% in the placebo groups achieved clinical remission at week 10. In patients previously treated with an anti-TNF agent or vedolizumab, 4.2% of patients receiving placebo compared to 11.5% taking filgotinib 200mg (P = 0.01) and 9.5% taking filgotinib 100 mg (P = .065) achieved clinical remission at week 10. Endoscopic remission was observed after induction therapy in 12.2% of patients receiving filgotinib 200 mg compared with 3.6% placebo in biologic naïve patients (P = .0047) and 3.4% of patients receiving filgotinib 200 mg compared to 2.1% of patients receiving placebo in biologic experienced patients (P = .43). Histologic remission was achieved in both biologic-naïve and biologic-experienced patients at the 200 mg dose significantly more frequently than in patients receiving placebo. At week 58, 37.2% of patients receiving filgotinib 200 mg and 11.2% of patients receiving placebo (P < .0001) were in clinical remission. In addition, 23.8% of patients receiving 100 mg were in clinical remission compared to 13.2% of patients in the placebo arm (P = .04). These results support that filgotinib may be another effective option for treating patients with moderate to severe ulcerative colitis.

Biosimilars to infliximab are increasingly used in clinical practice. Previous studies have demonstrated safety and efficacy of a single switch from originator to biosimilar infliximab. There is limited data, however, on performing multiple successive switches. In a multicenter prospective cohort, Hanzel et al evaluated 176 patients with inflammatory bowel disease (IBD). The investigators compared outcomes in three groups: group 1 (infliximab originator [INX] to CT-P13 to SB2; 2 switches), group 2 (CT-P13 to SB2; 1 switch) and group 3 (INX to CT-P13; 1 switch). After 12 months, there were no differences in the rates of clinical remission, treatment persistence, or fecal calprotectin. There were 3 infusion reactions in patients switched from CT-P13 to SB2 and none in the other 2 groups.  In conclusion, 2 switches of biosimilars in this prospective cohort were not associated with a change in effectiveness or safety.

The effectiveness of SARS-CoV2 vaccinations in an IBD population is not well known. In a retrospective cohort study with a median age of 68 years including 7376 unvaccinated and 7321 vaccinated veterans, Khan and Mahmud demonstrated the efficacy of full vaccination with the Pfizer or Moderna vaccine in preventing infection, severe infection, and death. In this cohort, less than half of patients were on a biologic or immunomodulator. Of the 6253 patients who were fully vaccinated, there were 7 infections and 3 serious infections compared to 197 infections, 47 serious infections, and 97 deaths in the 14,697 individuals monitored during an unvaccinated time period. Full vaccination (compared to unvaccinated) was 80.4% effective at preventing infection, 70.1% at preventing serious infection, and 87.3% effective and preventing all-cause mortality, whereas partial vaccination was 25.1% effective at preventing infection, 36.8% at preventing severe infection, and 27.3% at preventing all-cause mortality.

This study demonstrates the efficacy of full vaccination in patients with IBD with limited protection for patients receiving partial vaccination. It is limited by the fact that many patients considered unvaccinated may have been vaccinated outside the VA system, the relatively few numbers of events in vaccinated individuals, and lack of generalizability to other settings of patients with IBD as this study involved older men with relatively low rates of immunosuppression.

Janus kinase inhibitors (JAK inhibitors) have demonstrated efficacy in several immune mediated inflammatory conditions. Tofacitinib, which inhibits JAK3 and JAK1 greater than JAK2, was the first JAK inhibitor approved by the FDA for ulcerative colitis. In contrast to tofacitinib, filgotinib, preferentially inhibits JAK1. The efficacy of filgotinib during induction and maintenance therapy in ulcerative colitis was studied in a phase 2b/3 randomized control trial, the SELECTION trial. In this trial, 659 biologic-naïve and 689 biologic-experienced patients with moderate to severely active ulcerative colitis were randomized 2:2:1 to receive filgotinib 200mg daily, filgotinib 100mg daily, or placebo for 11 weeks. Responders to treatment with filgotinib at week 10 were rerandomized to their original dose or placebo in a 2:1 manner for a total treatment course of 58 weeks. The primary endpoint of the study was clinical remission which was defined as a Mayo endoscopy subscore of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency from baseline for a subscore of 0 or 1.

In biologic naïve patients, 26.1% of patients treated with filgotinib 200mg (P = .016) and 19.1% treated with filgotinib 100mg (P = 0.34) compared to 15.3% in the placebo groups achieved clinical remission at week 10. In patients previously treated with an anti-TNF agent or vedolizumab, 4.2% of patients receiving placebo compared to 11.5% taking filgotinib 200mg (P = 0.01) and 9.5% taking filgotinib 100 mg (P = .065) achieved clinical remission at week 10. Endoscopic remission was observed after induction therapy in 12.2% of patients receiving filgotinib 200 mg compared with 3.6% placebo in biologic naïve patients (P = .0047) and 3.4% of patients receiving filgotinib 200 mg compared to 2.1% of patients receiving placebo in biologic experienced patients (P = .43). Histologic remission was achieved in both biologic-naïve and biologic-experienced patients at the 200 mg dose significantly more frequently than in patients receiving placebo. At week 58, 37.2% of patients receiving filgotinib 200 mg and 11.2% of patients receiving placebo (P < .0001) were in clinical remission. In addition, 23.8% of patients receiving 100 mg were in clinical remission compared to 13.2% of patients in the placebo arm (P = .04). These results support that filgotinib may be another effective option for treating patients with moderate to severe ulcerative colitis.

Biosimilars to infliximab are increasingly used in clinical practice. Previous studies have demonstrated safety and efficacy of a single switch from originator to biosimilar infliximab. There is limited data, however, on performing multiple successive switches. In a multicenter prospective cohort, Hanzel et al evaluated 176 patients with inflammatory bowel disease (IBD). The investigators compared outcomes in three groups: group 1 (infliximab originator [INX] to CT-P13 to SB2; 2 switches), group 2 (CT-P13 to SB2; 1 switch) and group 3 (INX to CT-P13; 1 switch). After 12 months, there were no differences in the rates of clinical remission, treatment persistence, or fecal calprotectin. There were 3 infusion reactions in patients switched from CT-P13 to SB2 and none in the other 2 groups.  In conclusion, 2 switches of biosimilars in this prospective cohort were not associated with a change in effectiveness or safety.

The effectiveness of SARS-CoV2 vaccinations in an IBD population is not well known. In a retrospective cohort study with a median age of 68 years including 7376 unvaccinated and 7321 vaccinated veterans, Khan and Mahmud demonstrated the efficacy of full vaccination with the Pfizer or Moderna vaccine in preventing infection, severe infection, and death. In this cohort, less than half of patients were on a biologic or immunomodulator. Of the 6253 patients who were fully vaccinated, there were 7 infections and 3 serious infections compared to 197 infections, 47 serious infections, and 97 deaths in the 14,697 individuals monitored during an unvaccinated time period. Full vaccination (compared to unvaccinated) was 80.4% effective at preventing infection, 70.1% at preventing serious infection, and 87.3% effective and preventing all-cause mortality, whereas partial vaccination was 25.1% effective at preventing infection, 36.8% at preventing severe infection, and 27.3% at preventing all-cause mortality.

This study demonstrates the efficacy of full vaccination in patients with IBD with limited protection for patients receiving partial vaccination. It is limited by the fact that many patients considered unvaccinated may have been vaccinated outside the VA system, the relatively few numbers of events in vaccinated individuals, and lack of generalizability to other settings of patients with IBD as this study involved older men with relatively low rates of immunosuppression.

Janus kinase inhibitors (JAK inhibitors) have demonstrated efficacy in several immune mediated inflammatory conditions. Tofacitinib, which inhibits JAK3 and JAK1 greater than JAK2, was the first JAK inhibitor approved by the FDA for ulcerative colitis. In contrast to tofacitinib, filgotinib, preferentially inhibits JAK1. The efficacy of filgotinib during induction and maintenance therapy in ulcerative colitis was studied in a phase 2b/3 randomized control trial, the SELECTION trial. In this trial, 659 biologic-naïve and 689 biologic-experienced patients with moderate to severely active ulcerative colitis were randomized 2:2:1 to receive filgotinib 200mg daily, filgotinib 100mg daily, or placebo for 11 weeks. Responders to treatment with filgotinib at week 10 were rerandomized to their original dose or placebo in a 2:1 manner for a total treatment course of 58 weeks. The primary endpoint of the study was clinical remission which was defined as a Mayo endoscopy subscore of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency from baseline for a subscore of 0 or 1.

In biologic naïve patients, 26.1% of patients treated with filgotinib 200mg (P = .016) and 19.1% treated with filgotinib 100mg (P = 0.34) compared to 15.3% in the placebo groups achieved clinical remission at week 10. In patients previously treated with an anti-TNF agent or vedolizumab, 4.2% of patients receiving placebo compared to 11.5% taking filgotinib 200mg (P = 0.01) and 9.5% taking filgotinib 100 mg (P = .065) achieved clinical remission at week 10. Endoscopic remission was observed after induction therapy in 12.2% of patients receiving filgotinib 200 mg compared with 3.6% placebo in biologic naïve patients (P = .0047) and 3.4% of patients receiving filgotinib 200 mg compared to 2.1% of patients receiving placebo in biologic experienced patients (P = .43). Histologic remission was achieved in both biologic-naïve and biologic-experienced patients at the 200 mg dose significantly more frequently than in patients receiving placebo. At week 58, 37.2% of patients receiving filgotinib 200 mg and 11.2% of patients receiving placebo (P < .0001) were in clinical remission. In addition, 23.8% of patients receiving 100 mg were in clinical remission compared to 13.2% of patients in the placebo arm (P = .04). These results support that filgotinib may be another effective option for treating patients with moderate to severe ulcerative colitis.

Biosimilars to infliximab are increasingly used in clinical practice. Previous studies have demonstrated safety and efficacy of a single switch from originator to biosimilar infliximab. There is limited data, however, on performing multiple successive switches. In a multicenter prospective cohort, Hanzel et al evaluated 176 patients with inflammatory bowel disease (IBD). The investigators compared outcomes in three groups: group 1 (infliximab originator [INX] to CT-P13 to SB2; 2 switches), group 2 (CT-P13 to SB2; 1 switch) and group 3 (INX to CT-P13; 1 switch). After 12 months, there were no differences in the rates of clinical remission, treatment persistence, or fecal calprotectin. There were 3 infusion reactions in patients switched from CT-P13 to SB2 and none in the other 2 groups.  In conclusion, 2 switches of biosimilars in this prospective cohort were not associated with a change in effectiveness or safety.

The effectiveness of SARS-CoV2 vaccinations in an IBD population is not well known. In a retrospective cohort study with a median age of 68 years including 7376 unvaccinated and 7321 vaccinated veterans, Khan and Mahmud demonstrated the efficacy of full vaccination with the Pfizer or Moderna vaccine in preventing infection, severe infection, and death. In this cohort, less than half of patients were on a biologic or immunomodulator. Of the 6253 patients who were fully vaccinated, there were 7 infections and 3 serious infections compared to 197 infections, 47 serious infections, and 97 deaths in the 14,697 individuals monitored during an unvaccinated time period. Full vaccination (compared to unvaccinated) was 80.4% effective at preventing infection, 70.1% at preventing serious infection, and 87.3% effective and preventing all-cause mortality, whereas partial vaccination was 25.1% effective at preventing infection, 36.8% at preventing severe infection, and 27.3% at preventing all-cause mortality.

This study demonstrates the efficacy of full vaccination in patients with IBD with limited protection for patients receiving partial vaccination. It is limited by the fact that many patients considered unvaccinated may have been vaccinated outside the VA system, the relatively few numbers of events in vaccinated individuals, and lack of generalizability to other settings of patients with IBD as this study involved older men with relatively low rates of immunosuppression.

Choice of chemotherapy in metastatic colorectal cancer (mCRC): Age alone should not matter!

Consideration for chemotherapy in patients who are older has been limited to less intensive regimens. A recent study by Davis et al assessing the association of cumulative social risk and social support with receipt of chemotherapy among patients with mCRC confirmed that close to 40% of patients may not receive chemotherapy. Older age (≥65 years) was associated with a lower likelihood of chemotherapy receipt with an odds ratio (OR) of 0.28. Additional social risk (such as gender and/or race) further decreased the risk for not receiving chemotherapy. Identifying patients at risk and targeting them with patient support programs may help them with undergoing recommended treatment as per guidelines. The data from this study suggest that support from family and friends is beneficial and may allow patients to complete their chemotherapy treatment and consequently improve their long-term outcomes. In the absence of such support, any other source of support can mitigate the risk of nontreatment and should be strongly considered.

The study by Nakayama et al not only confirms the benefits of treating older patients but also shows evidence that those older than 80 years appear to derive a very similar benefit as younger patients with more intense chemotherapy. In this group of patients, intensive chemotherapy was defined as at least 2 courses of doublet chemotherapy with oxaliplatin- or irinotecan-based treatment. The results suggest a very similar survival outcomes for the aged and the younger patient groups with a hazard ratio (HR) of 1.29. Overall, this study suggests that older patients, including those older than 80 years, who may be eligible for intensive chemotherapy should not be excluded from this consideration based on their age alone. The option for intensive chemotherapy allows for eligible older patients to be exposed to a continuum of life extending therapies similar to younger patients.  Indeed, a recent prospective phase II study by Takahashi et al confirmed that trifluridine/tipiracil (FTD/TPI) was effective and well tolerated in elderly patients with mCRC and is in line with similar benefits historically observed in younger patients.

In conclusion, the cumulative knowledge from these studies confirms that identifying proper social support to older patients with mCRC will ensure that they are able to receive chemotherapy as indicated. It is also important to emphasize that age itself should not be a discriminator against the use of intensive chemotherapy and the opportunity to be exposed to the continuum of treatment options as indicated. It is understandable that for those older patients who may not be eligible for intensive chemotherapy, consideration for less intense therapy has been well validated in the past. At any point of the treatment continuum, as with any part of our oncologic care, discussion with patients and shared decision making is key to preserving the sacrosanct principles of patient autonomy and do no harm.

Choice of chemotherapy in metastatic colorectal cancer (mCRC): Age alone should not matter!

Consideration for chemotherapy in patients who are older has been limited to less intensive regimens. A recent study by Davis et al assessing the association of cumulative social risk and social support with receipt of chemotherapy among patients with mCRC confirmed that close to 40% of patients may not receive chemotherapy. Older age (≥65 years) was associated with a lower likelihood of chemotherapy receipt with an odds ratio (OR) of 0.28. Additional social risk (such as gender and/or race) further decreased the risk for not receiving chemotherapy. Identifying patients at risk and targeting them with patient support programs may help them with undergoing recommended treatment as per guidelines. The data from this study suggest that support from family and friends is beneficial and may allow patients to complete their chemotherapy treatment and consequently improve their long-term outcomes. In the absence of such support, any other source of support can mitigate the risk of nontreatment and should be strongly considered.

The study by Nakayama et al not only confirms the benefits of treating older patients but also shows evidence that those older than 80 years appear to derive a very similar benefit as younger patients with more intense chemotherapy. In this group of patients, intensive chemotherapy was defined as at least 2 courses of doublet chemotherapy with oxaliplatin- or irinotecan-based treatment. The results suggest a very similar survival outcomes for the aged and the younger patient groups with a hazard ratio (HR) of 1.29. Overall, this study suggests that older patients, including those older than 80 years, who may be eligible for intensive chemotherapy should not be excluded from this consideration based on their age alone. The option for intensive chemotherapy allows for eligible older patients to be exposed to a continuum of life extending therapies similar to younger patients.  Indeed, a recent prospective phase II study by Takahashi et al confirmed that trifluridine/tipiracil (FTD/TPI) was effective and well tolerated in elderly patients with mCRC and is in line with similar benefits historically observed in younger patients.

In conclusion, the cumulative knowledge from these studies confirms that identifying proper social support to older patients with mCRC will ensure that they are able to receive chemotherapy as indicated. It is also important to emphasize that age itself should not be a discriminator against the use of intensive chemotherapy and the opportunity to be exposed to the continuum of treatment options as indicated. It is understandable that for those older patients who may not be eligible for intensive chemotherapy, consideration for less intense therapy has been well validated in the past. At any point of the treatment continuum, as with any part of our oncologic care, discussion with patients and shared decision making is key to preserving the sacrosanct principles of patient autonomy and do no harm.

Choice of chemotherapy in metastatic colorectal cancer (mCRC): Age alone should not matter!

Consideration for chemotherapy in patients who are older has been limited to less intensive regimens. A recent study by Davis et al assessing the association of cumulative social risk and social support with receipt of chemotherapy among patients with mCRC confirmed that close to 40% of patients may not receive chemotherapy. Older age (≥65 years) was associated with a lower likelihood of chemotherapy receipt with an odds ratio (OR) of 0.28. Additional social risk (such as gender and/or race) further decreased the risk for not receiving chemotherapy. Identifying patients at risk and targeting them with patient support programs may help them with undergoing recommended treatment as per guidelines. The data from this study suggest that support from family and friends is beneficial and may allow patients to complete their chemotherapy treatment and consequently improve their long-term outcomes. In the absence of such support, any other source of support can mitigate the risk of nontreatment and should be strongly considered.

The study by Nakayama et al not only confirms the benefits of treating older patients but also shows evidence that those older than 80 years appear to derive a very similar benefit as younger patients with more intense chemotherapy. In this group of patients, intensive chemotherapy was defined as at least 2 courses of doublet chemotherapy with oxaliplatin- or irinotecan-based treatment. The results suggest a very similar survival outcomes for the aged and the younger patient groups with a hazard ratio (HR) of 1.29. Overall, this study suggests that older patients, including those older than 80 years, who may be eligible for intensive chemotherapy should not be excluded from this consideration based on their age alone. The option for intensive chemotherapy allows for eligible older patients to be exposed to a continuum of life extending therapies similar to younger patients.  Indeed, a recent prospective phase II study by Takahashi et al confirmed that trifluridine/tipiracil (FTD/TPI) was effective and well tolerated in elderly patients with mCRC and is in line with similar benefits historically observed in younger patients.

In conclusion, the cumulative knowledge from these studies confirms that identifying proper social support to older patients with mCRC will ensure that they are able to receive chemotherapy as indicated. It is also important to emphasize that age itself should not be a discriminator against the use of intensive chemotherapy and the opportunity to be exposed to the continuum of treatment options as indicated. It is understandable that for those older patients who may not be eligible for intensive chemotherapy, consideration for less intense therapy has been well validated in the past. At any point of the treatment continuum, as with any part of our oncologic care, discussion with patients and shared decision making is key to preserving the sacrosanct principles of patient autonomy and do no harm.

Treatment of hepatocellular carcinoma (HCC) benefits from a multidisciplinary approach. This month we will review some articles that address both localized and systemic therapies.

The first paper is a retrospective review of patients who underwent living donor liver transplantation (LDLT). Bhatti et al reviewed the outcomes of 244 patients with HCC who underwent LDLT at one center. All patients had AFP <1000 at time of LDLT. Out of those, 159 had tumors within UCSF criteria (single tumor ≤ 6.5 cm, up to 3 tumors ≤ 4.5 cm, total tumor diameter ≤ 8 cm), while 58 patients had tumors that were outside UCSF but <10cm, and 27 patients who were outside UCSF with macrovascular invasion (UCSF+). All patients within UCSF criteria were offered upfront LDLT. Patients outside UCSF criteria (UCSF+) were also considered for upfront LDLT, however patients with AFP >1000 ng/ml and UCSF + tumors were considered for downstaging. The authors reported that survival at 5 years was similar in the UCSF and UCSF+ groups (72% vs 69%, P = 0.7), while the rate of HCC recurrence was 13% vs 36% (P = 0.1). They concluded that carefully selected patients with HCC outside UCSF may benefit from LDLT.

Chemoembolization is a common treatment used for patients with localized HCC. Postembolization syndrome (abdominal pain, nausea, vomiting, fever and/or infection) is a frequent complication that adversely affects the patient’s quality of life. Lu et al report the results of a retrospective study of the use of dexamethasone in patients undergoing transarterial chemoembolization (TACE). The course of 255 HCC patients who underwent TACE were reviewed. The patients were divided into 2 nonrandomized groups to receive TACE using lipiodol + chemotherapeutic emulsion group (133 patients) or TACE using lipiodol + dexamethasone 10 mg + chemotherapeutic emulsion group (122 patients). Incidence of postembolization syndrome was reduced in the dexamethasone group: abdominal pain, 55.6% vs 36.1% (P = .002); fever, 37.6% vs 13.1% (P < .05); nausea, 60.9% vs 41.0% (P = .001); vomiting, 48.1% vs 21.3% (P < .05). Incidence of infection was 1.5% vs 2.5% (P = .583). The authors concluded that the incidence of postembolization syndrome could be reduced by adding dexamethasone to TACE.

Hepatic arterial infusion (HAI) chemotherapy has been used in the treatment of several types of liver-dominant tumors. Abdelmaksoud et al report on their experience using HAI to treat HCC with portal vein thrombosis and compensated cirrhosis. In this case-controlled study, 20 patients were treated with HAIC (50 mg doxorubicin and 50 mg cisplatin infused into the hepatic artery), 42 patients received best supportive care, and 29 patients were treated with sorafenib. The authors report that patients who received HAI had the longest survival compared with the best supportive care and sorafenib groups (29.2 ± 21.8, 4.55 ± 11.41, and 11.52 ± 8.72 months respectively, P = 0.007), concluding that HAI is an effective option for selected patients with HCC and portal vein thrombosis.

Finally, Hiraoka et al reported a retrospective study of 171 adults with unresectable HCC who received systemic therapy with atezolizumab with bevacizumab. In this report, only 75 patients received this as their first-line systemic therapy. After 6 weeks of treatment, the overall response rate was 10.6% (9.7% for previously treated and 12.2% for previously untreated), and the disease control rate was 79.6%.  In 111 patients, the albumin-bilirubin score that assesses liver function was significantly worse at 3 weeks after starting treatment (−2.525 ± 0.419 vs −2.323 ± 0.445, P < .001), but then recovered at 6-weeks, confirming the efficacy and safety of this treatment regimen.

Treatment of hepatocellular carcinoma (HCC) benefits from a multidisciplinary approach. This month we will review some articles that address both localized and systemic therapies.

The first paper is a retrospective review of patients who underwent living donor liver transplantation (LDLT). Bhatti et al reviewed the outcomes of 244 patients with HCC who underwent LDLT at one center. All patients had AFP <1000 at time of LDLT. Out of those, 159 had tumors within UCSF criteria (single tumor ≤ 6.5 cm, up to 3 tumors ≤ 4.5 cm, total tumor diameter ≤ 8 cm), while 58 patients had tumors that were outside UCSF but <10cm, and 27 patients who were outside UCSF with macrovascular invasion (UCSF+). All patients within UCSF criteria were offered upfront LDLT. Patients outside UCSF criteria (UCSF+) were also considered for upfront LDLT, however patients with AFP >1000 ng/ml and UCSF + tumors were considered for downstaging. The authors reported that survival at 5 years was similar in the UCSF and UCSF+ groups (72% vs 69%, P = 0.7), while the rate of HCC recurrence was 13% vs 36% (P = 0.1). They concluded that carefully selected patients with HCC outside UCSF may benefit from LDLT.

Chemoembolization is a common treatment used for patients with localized HCC. Postembolization syndrome (abdominal pain, nausea, vomiting, fever and/or infection) is a frequent complication that adversely affects the patient’s quality of life. Lu et al report the results of a retrospective study of the use of dexamethasone in patients undergoing transarterial chemoembolization (TACE). The course of 255 HCC patients who underwent TACE were reviewed. The patients were divided into 2 nonrandomized groups to receive TACE using lipiodol + chemotherapeutic emulsion group (133 patients) or TACE using lipiodol + dexamethasone 10 mg + chemotherapeutic emulsion group (122 patients). Incidence of postembolization syndrome was reduced in the dexamethasone group: abdominal pain, 55.6% vs 36.1% (P = .002); fever, 37.6% vs 13.1% (P < .05); nausea, 60.9% vs 41.0% (P = .001); vomiting, 48.1% vs 21.3% (P < .05). Incidence of infection was 1.5% vs 2.5% (P = .583). The authors concluded that the incidence of postembolization syndrome could be reduced by adding dexamethasone to TACE.

Hepatic arterial infusion (HAI) chemotherapy has been used in the treatment of several types of liver-dominant tumors. Abdelmaksoud et al report on their experience using HAI to treat HCC with portal vein thrombosis and compensated cirrhosis. In this case-controlled study, 20 patients were treated with HAIC (50 mg doxorubicin and 50 mg cisplatin infused into the hepatic artery), 42 patients received best supportive care, and 29 patients were treated with sorafenib. The authors report that patients who received HAI had the longest survival compared with the best supportive care and sorafenib groups (29.2 ± 21.8, 4.55 ± 11.41, and 11.52 ± 8.72 months respectively, P = 0.007), concluding that HAI is an effective option for selected patients with HCC and portal vein thrombosis.

Finally, Hiraoka et al reported a retrospective study of 171 adults with unresectable HCC who received systemic therapy with atezolizumab with bevacizumab. In this report, only 75 patients received this as their first-line systemic therapy. After 6 weeks of treatment, the overall response rate was 10.6% (9.7% for previously treated and 12.2% for previously untreated), and the disease control rate was 79.6%.  In 111 patients, the albumin-bilirubin score that assesses liver function was significantly worse at 3 weeks after starting treatment (−2.525 ± 0.419 vs −2.323 ± 0.445, P < .001), but then recovered at 6-weeks, confirming the efficacy and safety of this treatment regimen.

Treatment of hepatocellular carcinoma (HCC) benefits from a multidisciplinary approach. This month we will review some articles that address both localized and systemic therapies.

The first paper is a retrospective review of patients who underwent living donor liver transplantation (LDLT). Bhatti et al reviewed the outcomes of 244 patients with HCC who underwent LDLT at one center. All patients had AFP <1000 at time of LDLT. Out of those, 159 had tumors within UCSF criteria (single tumor ≤ 6.5 cm, up to 3 tumors ≤ 4.5 cm, total tumor diameter ≤ 8 cm), while 58 patients had tumors that were outside UCSF but <10cm, and 27 patients who were outside UCSF with macrovascular invasion (UCSF+). All patients within UCSF criteria were offered upfront LDLT. Patients outside UCSF criteria (UCSF+) were also considered for upfront LDLT, however patients with AFP >1000 ng/ml and UCSF + tumors were considered for downstaging. The authors reported that survival at 5 years was similar in the UCSF and UCSF+ groups (72% vs 69%, P = 0.7), while the rate of HCC recurrence was 13% vs 36% (P = 0.1). They concluded that carefully selected patients with HCC outside UCSF may benefit from LDLT.

Chemoembolization is a common treatment used for patients with localized HCC. Postembolization syndrome (abdominal pain, nausea, vomiting, fever and/or infection) is a frequent complication that adversely affects the patient’s quality of life. Lu et al report the results of a retrospective study of the use of dexamethasone in patients undergoing transarterial chemoembolization (TACE). The course of 255 HCC patients who underwent TACE were reviewed. The patients were divided into 2 nonrandomized groups to receive TACE using lipiodol + chemotherapeutic emulsion group (133 patients) or TACE using lipiodol + dexamethasone 10 mg + chemotherapeutic emulsion group (122 patients). Incidence of postembolization syndrome was reduced in the dexamethasone group: abdominal pain, 55.6% vs 36.1% (P = .002); fever, 37.6% vs 13.1% (P < .05); nausea, 60.9% vs 41.0% (P = .001); vomiting, 48.1% vs 21.3% (P < .05). Incidence of infection was 1.5% vs 2.5% (P = .583). The authors concluded that the incidence of postembolization syndrome could be reduced by adding dexamethasone to TACE.

Hepatic arterial infusion (HAI) chemotherapy has been used in the treatment of several types of liver-dominant tumors. Abdelmaksoud et al report on their experience using HAI to treat HCC with portal vein thrombosis and compensated cirrhosis. In this case-controlled study, 20 patients were treated with HAIC (50 mg doxorubicin and 50 mg cisplatin infused into the hepatic artery), 42 patients received best supportive care, and 29 patients were treated with sorafenib. The authors report that patients who received HAI had the longest survival compared with the best supportive care and sorafenib groups (29.2 ± 21.8, 4.55 ± 11.41, and 11.52 ± 8.72 months respectively, P = 0.007), concluding that HAI is an effective option for selected patients with HCC and portal vein thrombosis.

Finally, Hiraoka et al reported a retrospective study of 171 adults with unresectable HCC who received systemic therapy with atezolizumab with bevacizumab. In this report, only 75 patients received this as their first-line systemic therapy. After 6 weeks of treatment, the overall response rate was 10.6% (9.7% for previously treated and 12.2% for previously untreated), and the disease control rate was 79.6%.  In 111 patients, the albumin-bilirubin score that assesses liver function was significantly worse at 3 weeks after starting treatment (−2.525 ± 0.419 vs −2.323 ± 0.445, P < .001), but then recovered at 6-weeks, confirming the efficacy and safety of this treatment regimen.