ABSTRACT

Lesser tuberosity osteotomy (LTO) and subscapularis tenotomy (ST) are used for takedown of the subscapularis during shoulder arthroplasty. LTO offers the theoretical but unproven benefit of improved healing and function of the subscapularis. However, humeral stem subsidence and loosening may be greater when osteotomy is performed, which may compromise functional outcomes. Our hypothesis is that no difference in proximal collar press-fit humeral stem subsidence or loosening exists, with no impairment of functional outcomes using the LTO technique.

During the surgical approach for total shoulder arthroplasty (TSA), the subscapularis is taken down for adequate exposure to the glenohumeral joint. Various methods are available for taking down the subscapularis, including lesser tuberosity osteotomy (LTO) and a subscapularis tenotomy (ST). LTO offers the theoretical but unproven benefit of improved healing and function of the subscapularis secondary to bone-to-bone healing. One concern, however, is that humeral stem subsidence may be greater when an osteotomy is performed owing to compromise of metaphyseal cortical bone, which may compromise functional outcomes. The humeral stem design may also influence subsidence when metaphyseal bone proximally is compromised. This is a concern in both metaphyseal and diaphyseal fitting stems. Metaphyseal collars on diaphyseal fitting stems rely on adequate bone stock in the metaphysis to provide the additional support needed. Also, posterior subluxation remains a challenge in shoulder arthroplasty. The integrity of the subscapularis is important in prevention of posterior subluxation.¹ To our knowledge, no study to date has directly compared differences in humeral stem subsidence, loosening, or posterior subluxation between LTO and ST techniques with any humeral stem design. Our hypothesis is that no difference in proximal collar press-fit humeral stem subsidence or loosening exists, with no impairment of functional outcomes using the LTO technique. We also hypothesize that no difference in posterior subluxation exists between LTO and ST techniques.

MATERIALS AND METHODS

INCLUSION CRITERIA

Consecutive patients with a minimum of 12 months of radiographic follow-up were selected from 2007 to 2010 after TSA was performed by 1 of the senior authors (Dr. Miller and Dr. Voloshin). Study patients underwent primary TSA for primary osteoarthritis or rheumatoid arthritis.

EXCLUSION CRITERIA

Patients were excluded if they underwent TSA for posttraumatic glenohumeral arthritis, hemiarthroplasty, or osteonecrosis. Patients were also excluded if a rotator cuff tear was discovered intraoperatively or if they had a history of a rotator cuff repair. Additional exclusion criteria included postoperative trauma to the operative shoulder, postoperative infection, extensive documentation of chronic pain, and underlying neurologic disorder (eg, Parkinson disease, dystonia). Patients with a history of diabetes mellitus were not excluded.

SURGICAL TECHNIQUE

All patients underwent TSA via a deltopectoral approach in a modified beach chair position. Biceps tendons were tenodesed at the level of the pectoralis major. All patients received the same proximal collar press-fit implant (Bigliani-Flatow; Zimmer Biomet). These stems provide rotational stability in the metaphyseal segment via fins, vertical stability with the proximal collar, and distal fixation via an interference fit. All parts of the procedure were performed in similar fashion with the exception of ST vs LTO (Figures 1A-1D). 

Continue to: LTO was performed as the primary...

LESSER TUBEROSITY OSTEOTOMY

LTO was performed as the primary or preferred technique of 1 surgeon. After completion of the biceps tenodesis, the lesser tuberosity is reflected off with the subscapularis intact using an osteotome. After placement of the press-fit humeral stem, the LTO is repaired using No. 5 Ethibond Excel sutures (Ethicon) passed through previously created bone tunnels in the greater tuberosity. These sutures are tied over metal buttons over the lateral cortex of the greater tuberosity. Last, the lateral corner of the rotator interval is repaired using a single No. 2 FiberWire (Arthrex).²

SUBSCAPULARIS TENOTOMY

ST is the preferred surgical technique of the second surgeon. After a biceps tenodesis, the subscapularis tendon is released from the lesser tuberosity at the margin of the bicipital groove. Through careful dissection, a single flap including the underlying capsule is created and reflected medially to the level of the coracoid. After placement of the press-fit humeral stem and humeral head, the subscapularis is repaired back in place through previous bone tunnels and with a No. 5 Ethibond Excel suture under the appropriate tension. Then, the lateral corner of the rotator interval is closed using a single No. 2 Ethibond Excel suture in a figure-of-eight fashion.²

RADIOGRAPHIC ANALYSIS

The primary variables analyzed were subsidence and loosening. Additional variables, including humeral-acromial distance (HAD) and subluxation index, were also analyzed to assess for any additional impact caused by subsidence or loosening.³ All radiographic measurements were taken from the Grashey (true anteroposterior) view, except subluxation index, which was calculated using the axillary view. All radiographic measurements were completed by 3 independent reviewers. All radiographs were completed in a consistent manner according to postoperative protocols.

HAD was measured preoperatively, immediately postoperatively, and at final follow-up at a minimum of 1 year. The HAD was measured from the lowest point on the acromion to the humerus using a perpendicular line (Figure 2).

Subsidence of the prosthesis was calculated by determining the difference between immediate postoperative heights of the prosthesis in comparison to the value of the final follow-up films. To calculate the height, 2 lines were drawn, 1 line was drawn perpendicular to the top of the prosthetic head and 1 perpendicular to the top of the greater tuberosity (Figure 3). 

Continue to: Posterior subluxation is indicated...

The humeral stems were evaluated for loosening by assessing for lucency on final radiographic follow-up films. These were evaluated in a zonal fashion as demonstrated by Sanchez-Sotelo and colleagues⁴ and in Figure 5. 

FUNCTIONAL OUTCOME EVALUATION

Before clinical evaluation, each study patient completed the Western Ontario Osteoarthritis of the Shoulder (WOOS) index; the Disabilities of the Hand, Arm and Shoulder (DASH) questionnaire, and the pain and function sections of the Constant score. The functional outcomes scores were captured postoperatively from October to November 2011. The WOOS is a validated outcome measure specific to osteoarthritis of the shoulder and has been used in prior studies evaluating outcomes of TSA.^5-7 Previous studies have determined that the minimal clinically important difference for the WOOS score is 15 on a normalized 0 to 100 scale (100 being the best). The DASH score is a validated outcome measure for disorders of the upper extremity but is not specific to osteoarthritis of the shoulder.⁸ The Constant score is a validated outcome measure for a number of shoulder disorders, including TSA.^9,10

STATISTICAL ANALYSIS

Statistical analyses were completed by a trained biostatistician. A power analysis was calculated using the noninferiority test to determine if adequate data had been obtained for this study. This was calculated by using previously accepted data demonstrating a statistically significant difference for subsidence and HAD. The data from these studies were used to make assumptions regarding accepted standard deviations and noninferiority margins, as calculated from the mean values of the 2 groups analyzed in each respective study.^4,11 This analysis demonstrated power of 0.97 and 0.85 for the subsidence and HAD, respectively, given the current sample sizes. Intraclass coefficients were calculated to evaluate the measurements obtained during the radiographic analysis to determine the interrater agreement. Two samples’ t tests were calculated for the variables analyzed, along with P values and means.

RESULTS

DEMOGRAPHICS

A total of 51 consecutive patients were retrospectively selected for analysis. Of these, 16 patients were excluded from the study because they had <9 months of radiographic follow-up and were unavailable for further follow-up evaluation. Of the remaining 35 patients available for analysis, 4 patients had bilateral TSA, providing 39 shoulders for evaluation. Demographic characteristics of the study cohort are reported in Table 1.

  Fifteen patients underwent LTO, and 24 underwent ST. One patient underwent a tenotomy of the right shoulder and LTO of the left shoulder. Three LTOs were performed by the surgeon who primarily performed ST, owing to potential benefits of LTO. He eventually returned to his preferred technique of ST because of surgeon preference. Three ST procedures were completed by the surgeon who typically performed LTO at the start of the series prior to establishing LTO as his preferred technique. There was no significant difference between the study populations in terms of age, follow-up, male-to-female ratio, hand dominance, and primary diagnosis of osteoarthritis vs rheumatoid arthritis.

Continue to: There was no significant difference...

RADIOGRAPHIC DATA

There was no significant difference in preoperative HAD between the LTO and ST groups (9.5 ± 2.4 mm vs 10.9 ± 2.7 mm, P = .11). The immediate postoperative HAD was statistically significant between the LTO and ST groups (11.9 ± 3.7 mm vs 15.9 ± 4.5 mm, P = .005). There was as statistically significant difference noted in the final follow-up films between the LTO and ST groups (11.8 ± 3.2 mm vs 14.5 ± 3.9 mm, P = .025) (Table 2). 

Abbreviations: LTO, lesser tuberosity osteotomy; ST, subscapularis tenotomy.

There were no statistically significant differences found in subsidence between LTO and ST groups at final follow-up (2.8 mm ± 3.1 mm vs 2.5 mm ± 3.1 mm, P = .72) (Table 2). No statistically significant difference was noted in the subluxation index between the LTO and ST groups (0.55% ± .06% vs 0.54% ± 0.07%, P = .45), but there was a statistically significant difference noted postoperatively between the LTO and ST groups (0.55% ± 0.09% vs .48% ± 0.05%, P = .015) (Table 2).

Two stems were noted to have lucent lines >2 mm, both within the ST cohort. Each had 1 stem zone >2 mm, 1 in zone 7, and 1 in zone 4. No statistically significant difference was identified between the LTO and ST groups (0/15 vs 2/24, P = .51) (Table 2).

FUNCTIONAL OUTCOMES

Study patients were evaluated using functional outcome scores, including the Constant, WOOS, and DASH scores (Table 3). 

Abbreviations: DASH, disabilities of the arm, shoulder and hand; WOOS, Western Ontario Osteoarthritis of the Shoulder.

No statistically significant differences were noted in the DASH scores (8.4 ± 6.6 vs 13.8 ± 4.9, P = .13) or Constant scores (83.3 ± 9.1 vs 81.8 ± 10.1, P = .64) between the LTO and ST cohorts. There was a statistically significant difference between the WOOS scores (93.3 ± 5.3 vs 81.5 ± 20.8, P = .013). Because separate radiographic reviews were done by 3 independent personnel at 3 different times, it was important to ensure agreement among the reviewers. This was compared using the intraclass correlation coefficients. In the statistical analysis completed, the intraclass coefficients showed the 3 reviewers agreed with each other throughout the radiographic analysis (Table 4).

Abbreviations: CI, confidence interval; HAD, humeral acromial distance; ICC, intraclass correlation coefficient; SI, subluxation index.

DISCUSSION

At final follow-up, we identified no statistically significant difference between the LTO and ST patients in subsidence, lucent lines >2 mm, or functional outcomes (Constant and DASH scores) in patients who underwent TSA with the same proximal collar press-fit humeral stem. In regard to the functional outcome scores, although the WOOS score was statistically significant (P = .013) between the LTO and ST cohorts, we do not feel that this is clinically relevant because it does not reach the minimal clinically important difference threshold of 15 points.⁸

A statistically significant difference was noted in postoperative subluxation index but was not clinically relevant, because the values between the LTO and ST groups (0.55 vs 0.48) still showed a centered humeral head. Gerber and colleagues³ discussed using a value of 0.65 as a measure of posterior humeral head subluxation, whereas Walch and colleagues¹² defined posterior humeral head subluxation as a value >0.55. On the basis of these numbers, the values obtained in this study demonstrated that the postoperative values were still centered on the glenoid, and therefore were not clinically significant.^3,12

Continue to: In regard to HAD, there...

Studies have shown a concern regarding the integrity of the subscapularis after tenotomy or peel used in TSA with abnormal subscapularis function.^14,15 Miller and colleagues¹⁵ reported 41 patients, nearly two-thirds, of whom described subscapularis dysfunction. Those authors’ response to the poor clinical outcomes was to remove a fleck of bone with the tendon to achieve “bone-to-bone” healing.¹⁴ Gerber and colleagues¹⁶ reported on a series of patients using LTO and repair in TSA with 75% and 89% intact subscapularis function on clinical testing.¹⁶ Studies by Qureshi and colleagues¹⁷ and Scalise and colleagues¹⁸ showed similar results after LTO. Biomechanical studies have shown mixed results. Ponce and colleagues¹⁹ showed biomechanically superior results for LTO in comparison to the various repair techniques for ST. In another study, Giuseffi and colleagues²⁰ showed no difference in LTO vs ST during biomechanical testing. In response to the increased concern regarding subscapularis integrity, Caplan and colleagues²¹ reported on 45 arthroplasties in 43 patients with improved postoperative testing with intact subscapularis testing in 90% to 100% of patients. A level 1 randomized control trial conducted by Lapner and colleagues²² did not demonstrate any clear clinical advantage of LTO vs ST. Controversy still exists regarding which is the preferred technique for TSA.

Sanchez-Sotelo and colleagues⁴ evaluated uncemented humeral components in 72 patients who underwent TSA. They found a humeral component was at risk for loosening if a radiolucent line ≥2 mm was present in at least 3 radiographic zones. They also evaluated tilt or subsidence by measurement and whether the components were observed to have changed. Their measured values correlated with their observed values. That study provided a benchmark for evaluation of loosening and subsidence used during this study.⁴ Although radiographic follow-up is limited in this study, we feel that any potential subsidence secondary to use of the LTO technique would be radiographically apparent at 1 year. There were 16 patients without adequate radiographic follow-up included in the study. However, we feel that this was not a large concern, because the study was adequately powered with the patients available to determine a difference based on subsidence.

CONCLUSION

We found no difference in subsidence, lucent lines >2 mm, posterior subluxation, and the Constant and DASH functional outcome scores when we compared TSA performed by a LTO with an ST technique with proximal collar press-fit humeral stem. These data cannot be extrapolated to metaphyseal fit stems, which may exhibit different settling characteristics in the setting of the LTO technique.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

Lesser tuberosity osteotomy (LTO) and subscapularis tenotomy (ST) are used for takedown of the subscapularis during shoulder arthroplasty. LTO offers the theoretical but unproven benefit of improved healing and function of the subscapularis. However, humeral stem subsidence and loosening may be greater when osteotomy is performed, which may compromise functional outcomes. Our hypothesis is that no difference in proximal collar press-fit humeral stem subsidence or loosening exists, with no impairment of functional outcomes using the LTO technique.

During the surgical approach for total shoulder arthroplasty (TSA), the subscapularis is taken down for adequate exposure to the glenohumeral joint. Various methods are available for taking down the subscapularis, including lesser tuberosity osteotomy (LTO) and a subscapularis tenotomy (ST). LTO offers the theoretical but unproven benefit of improved healing and function of the subscapularis secondary to bone-to-bone healing. One concern, however, is that humeral stem subsidence may be greater when an osteotomy is performed owing to compromise of metaphyseal cortical bone, which may compromise functional outcomes. The humeral stem design may also influence subsidence when metaphyseal bone proximally is compromised. This is a concern in both metaphyseal and diaphyseal fitting stems. Metaphyseal collars on diaphyseal fitting stems rely on adequate bone stock in the metaphysis to provide the additional support needed. Also, posterior subluxation remains a challenge in shoulder arthroplasty. The integrity of the subscapularis is important in prevention of posterior subluxation.¹ To our knowledge, no study to date has directly compared differences in humeral stem subsidence, loosening, or posterior subluxation between LTO and ST techniques with any humeral stem design. Our hypothesis is that no difference in proximal collar press-fit humeral stem subsidence or loosening exists, with no impairment of functional outcomes using the LTO technique. We also hypothesize that no difference in posterior subluxation exists between LTO and ST techniques.

MATERIALS AND METHODS

INCLUSION CRITERIA

Consecutive patients with a minimum of 12 months of radiographic follow-up were selected from 2007 to 2010 after TSA was performed by 1 of the senior authors (Dr. Miller and Dr. Voloshin). Study patients underwent primary TSA for primary osteoarthritis or rheumatoid arthritis.

EXCLUSION CRITERIA

Patients were excluded if they underwent TSA for posttraumatic glenohumeral arthritis, hemiarthroplasty, or osteonecrosis. Patients were also excluded if a rotator cuff tear was discovered intraoperatively or if they had a history of a rotator cuff repair. Additional exclusion criteria included postoperative trauma to the operative shoulder, postoperative infection, extensive documentation of chronic pain, and underlying neurologic disorder (eg, Parkinson disease, dystonia). Patients with a history of diabetes mellitus were not excluded.

SURGICAL TECHNIQUE

All patients underwent TSA via a deltopectoral approach in a modified beach chair position. Biceps tendons were tenodesed at the level of the pectoralis major. All patients received the same proximal collar press-fit implant (Bigliani-Flatow; Zimmer Biomet). These stems provide rotational stability in the metaphyseal segment via fins, vertical stability with the proximal collar, and distal fixation via an interference fit. All parts of the procedure were performed in similar fashion with the exception of ST vs LTO (Figures 1A-1D). 

Continue to: LTO was performed as the primary...

LESSER TUBEROSITY OSTEOTOMY

LTO was performed as the primary or preferred technique of 1 surgeon. After completion of the biceps tenodesis, the lesser tuberosity is reflected off with the subscapularis intact using an osteotome. After placement of the press-fit humeral stem, the LTO is repaired using No. 5 Ethibond Excel sutures (Ethicon) passed through previously created bone tunnels in the greater tuberosity. These sutures are tied over metal buttons over the lateral cortex of the greater tuberosity. Last, the lateral corner of the rotator interval is repaired using a single No. 2 FiberWire (Arthrex).²

SUBSCAPULARIS TENOTOMY

ST is the preferred surgical technique of the second surgeon. After a biceps tenodesis, the subscapularis tendon is released from the lesser tuberosity at the margin of the bicipital groove. Through careful dissection, a single flap including the underlying capsule is created and reflected medially to the level of the coracoid. After placement of the press-fit humeral stem and humeral head, the subscapularis is repaired back in place through previous bone tunnels and with a No. 5 Ethibond Excel suture under the appropriate tension. Then, the lateral corner of the rotator interval is closed using a single No. 2 Ethibond Excel suture in a figure-of-eight fashion.²

RADIOGRAPHIC ANALYSIS

The primary variables analyzed were subsidence and loosening. Additional variables, including humeral-acromial distance (HAD) and subluxation index, were also analyzed to assess for any additional impact caused by subsidence or loosening.³ All radiographic measurements were taken from the Grashey (true anteroposterior) view, except subluxation index, which was calculated using the axillary view. All radiographic measurements were completed by 3 independent reviewers. All radiographs were completed in a consistent manner according to postoperative protocols.

HAD was measured preoperatively, immediately postoperatively, and at final follow-up at a minimum of 1 year. The HAD was measured from the lowest point on the acromion to the humerus using a perpendicular line (Figure 2).

Subsidence of the prosthesis was calculated by determining the difference between immediate postoperative heights of the prosthesis in comparison to the value of the final follow-up films. To calculate the height, 2 lines were drawn, 1 line was drawn perpendicular to the top of the prosthetic head and 1 perpendicular to the top of the greater tuberosity (Figure 3). 

Continue to: Posterior subluxation is indicated...

The humeral stems were evaluated for loosening by assessing for lucency on final radiographic follow-up films. These were evaluated in a zonal fashion as demonstrated by Sanchez-Sotelo and colleagues⁴ and in Figure 5. 

FUNCTIONAL OUTCOME EVALUATION

Before clinical evaluation, each study patient completed the Western Ontario Osteoarthritis of the Shoulder (WOOS) index; the Disabilities of the Hand, Arm and Shoulder (DASH) questionnaire, and the pain and function sections of the Constant score. The functional outcomes scores were captured postoperatively from October to November 2011. The WOOS is a validated outcome measure specific to osteoarthritis of the shoulder and has been used in prior studies evaluating outcomes of TSA.^5-7 Previous studies have determined that the minimal clinically important difference for the WOOS score is 15 on a normalized 0 to 100 scale (100 being the best). The DASH score is a validated outcome measure for disorders of the upper extremity but is not specific to osteoarthritis of the shoulder.⁸ The Constant score is a validated outcome measure for a number of shoulder disorders, including TSA.^9,10

STATISTICAL ANALYSIS

Statistical analyses were completed by a trained biostatistician. A power analysis was calculated using the noninferiority test to determine if adequate data had been obtained for this study. This was calculated by using previously accepted data demonstrating a statistically significant difference for subsidence and HAD. The data from these studies were used to make assumptions regarding accepted standard deviations and noninferiority margins, as calculated from the mean values of the 2 groups analyzed in each respective study.^4,11 This analysis demonstrated power of 0.97 and 0.85 for the subsidence and HAD, respectively, given the current sample sizes. Intraclass coefficients were calculated to evaluate the measurements obtained during the radiographic analysis to determine the interrater agreement. Two samples’ t tests were calculated for the variables analyzed, along with P values and means.

RESULTS

DEMOGRAPHICS

A total of 51 consecutive patients were retrospectively selected for analysis. Of these, 16 patients were excluded from the study because they had <9 months of radiographic follow-up and were unavailable for further follow-up evaluation. Of the remaining 35 patients available for analysis, 4 patients had bilateral TSA, providing 39 shoulders for evaluation. Demographic characteristics of the study cohort are reported in Table 1.

  Fifteen patients underwent LTO, and 24 underwent ST. One patient underwent a tenotomy of the right shoulder and LTO of the left shoulder. Three LTOs were performed by the surgeon who primarily performed ST, owing to potential benefits of LTO. He eventually returned to his preferred technique of ST because of surgeon preference. Three ST procedures were completed by the surgeon who typically performed LTO at the start of the series prior to establishing LTO as his preferred technique. There was no significant difference between the study populations in terms of age, follow-up, male-to-female ratio, hand dominance, and primary diagnosis of osteoarthritis vs rheumatoid arthritis.

Continue to: There was no significant difference...

RADIOGRAPHIC DATA

There was no significant difference in preoperative HAD between the LTO and ST groups (9.5 ± 2.4 mm vs 10.9 ± 2.7 mm, P = .11). The immediate postoperative HAD was statistically significant between the LTO and ST groups (11.9 ± 3.7 mm vs 15.9 ± 4.5 mm, P = .005). There was as statistically significant difference noted in the final follow-up films between the LTO and ST groups (11.8 ± 3.2 mm vs 14.5 ± 3.9 mm, P = .025) (Table 2). 

Abbreviations: LTO, lesser tuberosity osteotomy; ST, subscapularis tenotomy.

There were no statistically significant differences found in subsidence between LTO and ST groups at final follow-up (2.8 mm ± 3.1 mm vs 2.5 mm ± 3.1 mm, P = .72) (Table 2). No statistically significant difference was noted in the subluxation index between the LTO and ST groups (0.55% ± .06% vs 0.54% ± 0.07%, P = .45), but there was a statistically significant difference noted postoperatively between the LTO and ST groups (0.55% ± 0.09% vs .48% ± 0.05%, P = .015) (Table 2).

Two stems were noted to have lucent lines >2 mm, both within the ST cohort. Each had 1 stem zone >2 mm, 1 in zone 7, and 1 in zone 4. No statistically significant difference was identified between the LTO and ST groups (0/15 vs 2/24, P = .51) (Table 2).

FUNCTIONAL OUTCOMES

Study patients were evaluated using functional outcome scores, including the Constant, WOOS, and DASH scores (Table 3). 

Abbreviations: DASH, disabilities of the arm, shoulder and hand; WOOS, Western Ontario Osteoarthritis of the Shoulder.

No statistically significant differences were noted in the DASH scores (8.4 ± 6.6 vs 13.8 ± 4.9, P = .13) or Constant scores (83.3 ± 9.1 vs 81.8 ± 10.1, P = .64) between the LTO and ST cohorts. There was a statistically significant difference between the WOOS scores (93.3 ± 5.3 vs 81.5 ± 20.8, P = .013). Because separate radiographic reviews were done by 3 independent personnel at 3 different times, it was important to ensure agreement among the reviewers. This was compared using the intraclass correlation coefficients. In the statistical analysis completed, the intraclass coefficients showed the 3 reviewers agreed with each other throughout the radiographic analysis (Table 4).

Abbreviations: CI, confidence interval; HAD, humeral acromial distance; ICC, intraclass correlation coefficient; SI, subluxation index.

DISCUSSION

At final follow-up, we identified no statistically significant difference between the LTO and ST patients in subsidence, lucent lines >2 mm, or functional outcomes (Constant and DASH scores) in patients who underwent TSA with the same proximal collar press-fit humeral stem. In regard to the functional outcome scores, although the WOOS score was statistically significant (P = .013) between the LTO and ST cohorts, we do not feel that this is clinically relevant because it does not reach the minimal clinically important difference threshold of 15 points.⁸

A statistically significant difference was noted in postoperative subluxation index but was not clinically relevant, because the values between the LTO and ST groups (0.55 vs 0.48) still showed a centered humeral head. Gerber and colleagues³ discussed using a value of 0.65 as a measure of posterior humeral head subluxation, whereas Walch and colleagues¹² defined posterior humeral head subluxation as a value >0.55. On the basis of these numbers, the values obtained in this study demonstrated that the postoperative values were still centered on the glenoid, and therefore were not clinically significant.^3,12

Continue to: In regard to HAD, there...

Studies have shown a concern regarding the integrity of the subscapularis after tenotomy or peel used in TSA with abnormal subscapularis function.^14,15 Miller and colleagues¹⁵ reported 41 patients, nearly two-thirds, of whom described subscapularis dysfunction. Those authors’ response to the poor clinical outcomes was to remove a fleck of bone with the tendon to achieve “bone-to-bone” healing.¹⁴ Gerber and colleagues¹⁶ reported on a series of patients using LTO and repair in TSA with 75% and 89% intact subscapularis function on clinical testing.¹⁶ Studies by Qureshi and colleagues¹⁷ and Scalise and colleagues¹⁸ showed similar results after LTO. Biomechanical studies have shown mixed results. Ponce and colleagues¹⁹ showed biomechanically superior results for LTO in comparison to the various repair techniques for ST. In another study, Giuseffi and colleagues²⁰ showed no difference in LTO vs ST during biomechanical testing. In response to the increased concern regarding subscapularis integrity, Caplan and colleagues²¹ reported on 45 arthroplasties in 43 patients with improved postoperative testing with intact subscapularis testing in 90% to 100% of patients. A level 1 randomized control trial conducted by Lapner and colleagues²² did not demonstrate any clear clinical advantage of LTO vs ST. Controversy still exists regarding which is the preferred technique for TSA.

Sanchez-Sotelo and colleagues⁴ evaluated uncemented humeral components in 72 patients who underwent TSA. They found a humeral component was at risk for loosening if a radiolucent line ≥2 mm was present in at least 3 radiographic zones. They also evaluated tilt or subsidence by measurement and whether the components were observed to have changed. Their measured values correlated with their observed values. That study provided a benchmark for evaluation of loosening and subsidence used during this study.⁴ Although radiographic follow-up is limited in this study, we feel that any potential subsidence secondary to use of the LTO technique would be radiographically apparent at 1 year. There were 16 patients without adequate radiographic follow-up included in the study. However, we feel that this was not a large concern, because the study was adequately powered with the patients available to determine a difference based on subsidence.

CONCLUSION

We found no difference in subsidence, lucent lines >2 mm, posterior subluxation, and the Constant and DASH functional outcome scores when we compared TSA performed by a LTO with an ST technique with proximal collar press-fit humeral stem. These data cannot be extrapolated to metaphyseal fit stems, which may exhibit different settling characteristics in the setting of the LTO technique.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

Lesser tuberosity osteotomy (LTO) and subscapularis tenotomy (ST) are used for takedown of the subscapularis during shoulder arthroplasty. LTO offers the theoretical but unproven benefit of improved healing and function of the subscapularis. However, humeral stem subsidence and loosening may be greater when osteotomy is performed, which may compromise functional outcomes. Our hypothesis is that no difference in proximal collar press-fit humeral stem subsidence or loosening exists, with no impairment of functional outcomes using the LTO technique.

During the surgical approach for total shoulder arthroplasty (TSA), the subscapularis is taken down for adequate exposure to the glenohumeral joint. Various methods are available for taking down the subscapularis, including lesser tuberosity osteotomy (LTO) and a subscapularis tenotomy (ST). LTO offers the theoretical but unproven benefit of improved healing and function of the subscapularis secondary to bone-to-bone healing. One concern, however, is that humeral stem subsidence may be greater when an osteotomy is performed owing to compromise of metaphyseal cortical bone, which may compromise functional outcomes. The humeral stem design may also influence subsidence when metaphyseal bone proximally is compromised. This is a concern in both metaphyseal and diaphyseal fitting stems. Metaphyseal collars on diaphyseal fitting stems rely on adequate bone stock in the metaphysis to provide the additional support needed. Also, posterior subluxation remains a challenge in shoulder arthroplasty. The integrity of the subscapularis is important in prevention of posterior subluxation.¹ To our knowledge, no study to date has directly compared differences in humeral stem subsidence, loosening, or posterior subluxation between LTO and ST techniques with any humeral stem design. Our hypothesis is that no difference in proximal collar press-fit humeral stem subsidence or loosening exists, with no impairment of functional outcomes using the LTO technique. We also hypothesize that no difference in posterior subluxation exists between LTO and ST techniques.

MATERIALS AND METHODS

INCLUSION CRITERIA

Consecutive patients with a minimum of 12 months of radiographic follow-up were selected from 2007 to 2010 after TSA was performed by 1 of the senior authors (Dr. Miller and Dr. Voloshin). Study patients underwent primary TSA for primary osteoarthritis or rheumatoid arthritis.

EXCLUSION CRITERIA

Patients were excluded if they underwent TSA for posttraumatic glenohumeral arthritis, hemiarthroplasty, or osteonecrosis. Patients were also excluded if a rotator cuff tear was discovered intraoperatively or if they had a history of a rotator cuff repair. Additional exclusion criteria included postoperative trauma to the operative shoulder, postoperative infection, extensive documentation of chronic pain, and underlying neurologic disorder (eg, Parkinson disease, dystonia). Patients with a history of diabetes mellitus were not excluded.

SURGICAL TECHNIQUE

All patients underwent TSA via a deltopectoral approach in a modified beach chair position. Biceps tendons were tenodesed at the level of the pectoralis major. All patients received the same proximal collar press-fit implant (Bigliani-Flatow; Zimmer Biomet). These stems provide rotational stability in the metaphyseal segment via fins, vertical stability with the proximal collar, and distal fixation via an interference fit. All parts of the procedure were performed in similar fashion with the exception of ST vs LTO (Figures 1A-1D). 

Continue to: LTO was performed as the primary...

LESSER TUBEROSITY OSTEOTOMY

LTO was performed as the primary or preferred technique of 1 surgeon. After completion of the biceps tenodesis, the lesser tuberosity is reflected off with the subscapularis intact using an osteotome. After placement of the press-fit humeral stem, the LTO is repaired using No. 5 Ethibond Excel sutures (Ethicon) passed through previously created bone tunnels in the greater tuberosity. These sutures are tied over metal buttons over the lateral cortex of the greater tuberosity. Last, the lateral corner of the rotator interval is repaired using a single No. 2 FiberWire (Arthrex).²

SUBSCAPULARIS TENOTOMY

ST is the preferred surgical technique of the second surgeon. After a biceps tenodesis, the subscapularis tendon is released from the lesser tuberosity at the margin of the bicipital groove. Through careful dissection, a single flap including the underlying capsule is created and reflected medially to the level of the coracoid. After placement of the press-fit humeral stem and humeral head, the subscapularis is repaired back in place through previous bone tunnels and with a No. 5 Ethibond Excel suture under the appropriate tension. Then, the lateral corner of the rotator interval is closed using a single No. 2 Ethibond Excel suture in a figure-of-eight fashion.²

RADIOGRAPHIC ANALYSIS

The primary variables analyzed were subsidence and loosening. Additional variables, including humeral-acromial distance (HAD) and subluxation index, were also analyzed to assess for any additional impact caused by subsidence or loosening.³ All radiographic measurements were taken from the Grashey (true anteroposterior) view, except subluxation index, which was calculated using the axillary view. All radiographic measurements were completed by 3 independent reviewers. All radiographs were completed in a consistent manner according to postoperative protocols.

HAD was measured preoperatively, immediately postoperatively, and at final follow-up at a minimum of 1 year. The HAD was measured from the lowest point on the acromion to the humerus using a perpendicular line (Figure 2).

Subsidence of the prosthesis was calculated by determining the difference between immediate postoperative heights of the prosthesis in comparison to the value of the final follow-up films. To calculate the height, 2 lines were drawn, 1 line was drawn perpendicular to the top of the prosthetic head and 1 perpendicular to the top of the greater tuberosity (Figure 3). 

Continue to: Posterior subluxation is indicated...

The humeral stems were evaluated for loosening by assessing for lucency on final radiographic follow-up films. These were evaluated in a zonal fashion as demonstrated by Sanchez-Sotelo and colleagues⁴ and in Figure 5. 

FUNCTIONAL OUTCOME EVALUATION

Before clinical evaluation, each study patient completed the Western Ontario Osteoarthritis of the Shoulder (WOOS) index; the Disabilities of the Hand, Arm and Shoulder (DASH) questionnaire, and the pain and function sections of the Constant score. The functional outcomes scores were captured postoperatively from October to November 2011. The WOOS is a validated outcome measure specific to osteoarthritis of the shoulder and has been used in prior studies evaluating outcomes of TSA.^5-7 Previous studies have determined that the minimal clinically important difference for the WOOS score is 15 on a normalized 0 to 100 scale (100 being the best). The DASH score is a validated outcome measure for disorders of the upper extremity but is not specific to osteoarthritis of the shoulder.⁸ The Constant score is a validated outcome measure for a number of shoulder disorders, including TSA.^9,10

STATISTICAL ANALYSIS

Statistical analyses were completed by a trained biostatistician. A power analysis was calculated using the noninferiority test to determine if adequate data had been obtained for this study. This was calculated by using previously accepted data demonstrating a statistically significant difference for subsidence and HAD. The data from these studies were used to make assumptions regarding accepted standard deviations and noninferiority margins, as calculated from the mean values of the 2 groups analyzed in each respective study.^4,11 This analysis demonstrated power of 0.97 and 0.85 for the subsidence and HAD, respectively, given the current sample sizes. Intraclass coefficients were calculated to evaluate the measurements obtained during the radiographic analysis to determine the interrater agreement. Two samples’ t tests were calculated for the variables analyzed, along with P values and means.

RESULTS

DEMOGRAPHICS

A total of 51 consecutive patients were retrospectively selected for analysis. Of these, 16 patients were excluded from the study because they had <9 months of radiographic follow-up and were unavailable for further follow-up evaluation. Of the remaining 35 patients available for analysis, 4 patients had bilateral TSA, providing 39 shoulders for evaluation. Demographic characteristics of the study cohort are reported in Table 1.

  Fifteen patients underwent LTO, and 24 underwent ST. One patient underwent a tenotomy of the right shoulder and LTO of the left shoulder. Three LTOs were performed by the surgeon who primarily performed ST, owing to potential benefits of LTO. He eventually returned to his preferred technique of ST because of surgeon preference. Three ST procedures were completed by the surgeon who typically performed LTO at the start of the series prior to establishing LTO as his preferred technique. There was no significant difference between the study populations in terms of age, follow-up, male-to-female ratio, hand dominance, and primary diagnosis of osteoarthritis vs rheumatoid arthritis.

Continue to: There was no significant difference...

RADIOGRAPHIC DATA

There was no significant difference in preoperative HAD between the LTO and ST groups (9.5 ± 2.4 mm vs 10.9 ± 2.7 mm, P = .11). The immediate postoperative HAD was statistically significant between the LTO and ST groups (11.9 ± 3.7 mm vs 15.9 ± 4.5 mm, P = .005). There was as statistically significant difference noted in the final follow-up films between the LTO and ST groups (11.8 ± 3.2 mm vs 14.5 ± 3.9 mm, P = .025) (Table 2). 

Abbreviations: LTO, lesser tuberosity osteotomy; ST, subscapularis tenotomy.

There were no statistically significant differences found in subsidence between LTO and ST groups at final follow-up (2.8 mm ± 3.1 mm vs 2.5 mm ± 3.1 mm, P = .72) (Table 2). No statistically significant difference was noted in the subluxation index between the LTO and ST groups (0.55% ± .06% vs 0.54% ± 0.07%, P = .45), but there was a statistically significant difference noted postoperatively between the LTO and ST groups (0.55% ± 0.09% vs .48% ± 0.05%, P = .015) (Table 2).

Two stems were noted to have lucent lines >2 mm, both within the ST cohort. Each had 1 stem zone >2 mm, 1 in zone 7, and 1 in zone 4. No statistically significant difference was identified between the LTO and ST groups (0/15 vs 2/24, P = .51) (Table 2).

FUNCTIONAL OUTCOMES

Study patients were evaluated using functional outcome scores, including the Constant, WOOS, and DASH scores (Table 3). 

Abbreviations: DASH, disabilities of the arm, shoulder and hand; WOOS, Western Ontario Osteoarthritis of the Shoulder.

No statistically significant differences were noted in the DASH scores (8.4 ± 6.6 vs 13.8 ± 4.9, P = .13) or Constant scores (83.3 ± 9.1 vs 81.8 ± 10.1, P = .64) between the LTO and ST cohorts. There was a statistically significant difference between the WOOS scores (93.3 ± 5.3 vs 81.5 ± 20.8, P = .013). Because separate radiographic reviews were done by 3 independent personnel at 3 different times, it was important to ensure agreement among the reviewers. This was compared using the intraclass correlation coefficients. In the statistical analysis completed, the intraclass coefficients showed the 3 reviewers agreed with each other throughout the radiographic analysis (Table 4).

Abbreviations: CI, confidence interval; HAD, humeral acromial distance; ICC, intraclass correlation coefficient; SI, subluxation index.

DISCUSSION

At final follow-up, we identified no statistically significant difference between the LTO and ST patients in subsidence, lucent lines >2 mm, or functional outcomes (Constant and DASH scores) in patients who underwent TSA with the same proximal collar press-fit humeral stem. In regard to the functional outcome scores, although the WOOS score was statistically significant (P = .013) between the LTO and ST cohorts, we do not feel that this is clinically relevant because it does not reach the minimal clinically important difference threshold of 15 points.⁸

A statistically significant difference was noted in postoperative subluxation index but was not clinically relevant, because the values between the LTO and ST groups (0.55 vs 0.48) still showed a centered humeral head. Gerber and colleagues³ discussed using a value of 0.65 as a measure of posterior humeral head subluxation, whereas Walch and colleagues¹² defined posterior humeral head subluxation as a value >0.55. On the basis of these numbers, the values obtained in this study demonstrated that the postoperative values were still centered on the glenoid, and therefore were not clinically significant.^3,12

Continue to: In regard to HAD, there...

Studies have shown a concern regarding the integrity of the subscapularis after tenotomy or peel used in TSA with abnormal subscapularis function.^14,15 Miller and colleagues¹⁵ reported 41 patients, nearly two-thirds, of whom described subscapularis dysfunction. Those authors’ response to the poor clinical outcomes was to remove a fleck of bone with the tendon to achieve “bone-to-bone” healing.¹⁴ Gerber and colleagues¹⁶ reported on a series of patients using LTO and repair in TSA with 75% and 89% intact subscapularis function on clinical testing.¹⁶ Studies by Qureshi and colleagues¹⁷ and Scalise and colleagues¹⁸ showed similar results after LTO. Biomechanical studies have shown mixed results. Ponce and colleagues¹⁹ showed biomechanically superior results for LTO in comparison to the various repair techniques for ST. In another study, Giuseffi and colleagues²⁰ showed no difference in LTO vs ST during biomechanical testing. In response to the increased concern regarding subscapularis integrity, Caplan and colleagues²¹ reported on 45 arthroplasties in 43 patients with improved postoperative testing with intact subscapularis testing in 90% to 100% of patients. A level 1 randomized control trial conducted by Lapner and colleagues²² did not demonstrate any clear clinical advantage of LTO vs ST. Controversy still exists regarding which is the preferred technique for TSA.

Sanchez-Sotelo and colleagues⁴ evaluated uncemented humeral components in 72 patients who underwent TSA. They found a humeral component was at risk for loosening if a radiolucent line ≥2 mm was present in at least 3 radiographic zones. They also evaluated tilt or subsidence by measurement and whether the components were observed to have changed. Their measured values correlated with their observed values. That study provided a benchmark for evaluation of loosening and subsidence used during this study.⁴ Although radiographic follow-up is limited in this study, we feel that any potential subsidence secondary to use of the LTO technique would be radiographically apparent at 1 year. There were 16 patients without adequate radiographic follow-up included in the study. However, we feel that this was not a large concern, because the study was adequately powered with the patients available to determine a difference based on subsidence.

CONCLUSION

We found no difference in subsidence, lucent lines >2 mm, posterior subluxation, and the Constant and DASH functional outcome scores when we compared TSA performed by a LTO with an ST technique with proximal collar press-fit humeral stem. These data cannot be extrapolated to metaphyseal fit stems, which may exhibit different settling characteristics in the setting of the LTO technique.

This paper will be judged for the Resident Writer’s Award.

Vidyard Video

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Additional videos from SGS are available here, including these recent offerings:

• Basic technique of vaginal hysterectomy
• Uterosacral ligament colpopexy: The way we do it
• Surgical anatomy and steps of the uterosacral ligament colpopexy

Vidyard Video

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Additional videos from SGS are available here, including these recent offerings:

• Basic technique of vaginal hysterectomy
• Uterosacral ligament colpopexy: The way we do it
• Surgical anatomy and steps of the uterosacral ligament colpopexy

Vidyard Video

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Additional videos from SGS are available here, including these recent offerings:

• Basic technique of vaginal hysterectomy
• Uterosacral ligament colpopexy: The way we do it
• Surgical anatomy and steps of the uterosacral ligament colpopexy

The CURESZ Foundation was founded in 2016 to bring hope to people suffering from schizophrenia and those who love and care for them. CURESZ was established by Bethany Yeiser and her psychiatrist, Current Psychiatry Editor-in-Chief Henry Nasrallah, MD, and was inspired by Bethany's complete recovery from schizophrenia after 4 years of delusions, hallucinations, homelessness, and disability. Bethany returned to her normal life and graduated from college with honors, thanks to clozapine, which cured her symptoms when several other medications did not work (for more of Bethany’s story, see From the Editor, Current Psychiatry. October 2014, p. 21,24-25).

We previously assembled a panel of clozapine experts  to whom the CURESZ Foundation would refer patients who have never had a trial of clozapine despite ongoing delusions or hallucinations.  We now have a panel of 80 clozapine experts around the country who are willing to receive referrals.

 In an unexpected turn of events, after several years of receiving clozapine, Bethany developed tardive dyskinesia (TD) which,  fortunately,  was successfully treated. Bethany would not have been able to recover from  her TD had it not been for the recent FDA approval of effective treatments.   The embarrassing personal experience of oro-buccal TD movements  that Bethany went through before she improved led her and me to establish a panel of experts in the recognition and treatment of TD around the country. It is estimated that hundreds of thousands of patients with schizophrenia, schizo-affective disorders, bipolar disorder and major depression, all of whom receive first or second generation antipsychotic agents, currently have TD that is not being diagnosed or treated.

We are therefore calling for psychiatric practitioners who have had experience in recognizing TD movements and have treated patients with FDA-approved treatments,  to contact the CURESZ Foundation. Henry Nasrallah, MD, the Scientific Director of the CURESZ Foundation, who has had many years of federally funded research experience  in TD, will serve as the Chair of this TD Panel. 

This is a call for readers of Current Psychiatry who are treating TD  and who practice in settings that can accommodate additional patients seeking treatment for their involuntary TD muscle movements in their face, trunk, and extremities. We hope to assemble between 50 to 100 experts to join this national TD panel.

If you would like to be a member of this national CURESZ TD Panel, please go to  https://curesz.org/tardive-dyskinesia-panel/ and enter your name, email, work address, and office phone number. We will later organize the list by state and city so that patients and families around the country can contact the nearest expert to get an evaluation for assessment and treatment of their TD.

Thank you and we look forward to working with the experts who say “YESZ” to joining the TD Panel, sponsored by the CURESZ Foundation.

The CURESZ Foundation was founded in 2016 to bring hope to people suffering from schizophrenia and those who love and care for them. CURESZ was established by Bethany Yeiser and her psychiatrist, Current Psychiatry Editor-in-Chief Henry Nasrallah, MD, and was inspired by Bethany's complete recovery from schizophrenia after 4 years of delusions, hallucinations, homelessness, and disability. Bethany returned to her normal life and graduated from college with honors, thanks to clozapine, which cured her symptoms when several other medications did not work (for more of Bethany’s story, see From the Editor, Current Psychiatry. October 2014, p. 21,24-25).

We previously assembled a panel of clozapine experts  to whom the CURESZ Foundation would refer patients who have never had a trial of clozapine despite ongoing delusions or hallucinations.  We now have a panel of 80 clozapine experts around the country who are willing to receive referrals.

 In an unexpected turn of events, after several years of receiving clozapine, Bethany developed tardive dyskinesia (TD) which,  fortunately,  was successfully treated. Bethany would not have been able to recover from  her TD had it not been for the recent FDA approval of effective treatments.   The embarrassing personal experience of oro-buccal TD movements  that Bethany went through before she improved led her and me to establish a panel of experts in the recognition and treatment of TD around the country. It is estimated that hundreds of thousands of patients with schizophrenia, schizo-affective disorders, bipolar disorder and major depression, all of whom receive first or second generation antipsychotic agents, currently have TD that is not being diagnosed or treated.

We are therefore calling for psychiatric practitioners who have had experience in recognizing TD movements and have treated patients with FDA-approved treatments,  to contact the CURESZ Foundation. Henry Nasrallah, MD, the Scientific Director of the CURESZ Foundation, who has had many years of federally funded research experience  in TD, will serve as the Chair of this TD Panel. 

This is a call for readers of Current Psychiatry who are treating TD  and who practice in settings that can accommodate additional patients seeking treatment for their involuntary TD muscle movements in their face, trunk, and extremities. We hope to assemble between 50 to 100 experts to join this national TD panel.

If you would like to be a member of this national CURESZ TD Panel, please go to  https://curesz.org/tardive-dyskinesia-panel/ and enter your name, email, work address, and office phone number. We will later organize the list by state and city so that patients and families around the country can contact the nearest expert to get an evaluation for assessment and treatment of their TD.

Thank you and we look forward to working with the experts who say “YESZ” to joining the TD Panel, sponsored by the CURESZ Foundation.

The CURESZ Foundation was founded in 2016 to bring hope to people suffering from schizophrenia and those who love and care for them. CURESZ was established by Bethany Yeiser and her psychiatrist, Current Psychiatry Editor-in-Chief Henry Nasrallah, MD, and was inspired by Bethany's complete recovery from schizophrenia after 4 years of delusions, hallucinations, homelessness, and disability. Bethany returned to her normal life and graduated from college with honors, thanks to clozapine, which cured her symptoms when several other medications did not work (for more of Bethany’s story, see From the Editor, Current Psychiatry. October 2014, p. 21,24-25).

We previously assembled a panel of clozapine experts  to whom the CURESZ Foundation would refer patients who have never had a trial of clozapine despite ongoing delusions or hallucinations.  We now have a panel of 80 clozapine experts around the country who are willing to receive referrals.

 In an unexpected turn of events, after several years of receiving clozapine, Bethany developed tardive dyskinesia (TD) which,  fortunately,  was successfully treated. Bethany would not have been able to recover from  her TD had it not been for the recent FDA approval of effective treatments.   The embarrassing personal experience of oro-buccal TD movements  that Bethany went through before she improved led her and me to establish a panel of experts in the recognition and treatment of TD around the country. It is estimated that hundreds of thousands of patients with schizophrenia, schizo-affective disorders, bipolar disorder and major depression, all of whom receive first or second generation antipsychotic agents, currently have TD that is not being diagnosed or treated.

We are therefore calling for psychiatric practitioners who have had experience in recognizing TD movements and have treated patients with FDA-approved treatments,  to contact the CURESZ Foundation. Henry Nasrallah, MD, the Scientific Director of the CURESZ Foundation, who has had many years of federally funded research experience  in TD, will serve as the Chair of this TD Panel. 

This is a call for readers of Current Psychiatry who are treating TD  and who practice in settings that can accommodate additional patients seeking treatment for their involuntary TD muscle movements in their face, trunk, and extremities. We hope to assemble between 50 to 100 experts to join this national TD panel.

If you would like to be a member of this national CURESZ TD Panel, please go to  https://curesz.org/tardive-dyskinesia-panel/ and enter your name, email, work address, and office phone number. We will later organize the list by state and city so that patients and families around the country can contact the nearest expert to get an evaluation for assessment and treatment of their TD.

Thank you and we look forward to working with the experts who say “YESZ” to joining the TD Panel, sponsored by the CURESZ Foundation.

The Food and Drug Administration has approved Prolia (denosumab) for the treatment of glucocorticoid-induced osteoporosis in adults at high risk of fracture, the drug’s manufacturer Amgen announced May 21.

FDA approval was based on 12-month primary analysis results from a randomized, double-blind, phase 3 trial. Patients who received a 60-mg dose of Prolia subcutaneously every 6 months had greater lumbar spine bone mineral density at 1 year than did those who received a 5-mg dose of risedronate daily in all study subpopulations. These results were maintained after researchers controlled for gender, race, geographic region, and menopausal status, as well as baseline age, lumbar spine bone mineral density T score, and glucocorticoid dose within each subpopulation.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The most common adverse events associated with Prolia during the phase 3 study were back pain, hypertension, bronchitis, and headache, which are in line with previously reported safety data.

“Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in bone mineral density within a few months of beginning treatment. With this approval, patients who receive treatment with glucocorticoids now have a new option to help improve their bone mineral density,” lead study author Kenneth F. Saag, MD, professor of medicine at the University of Alabama, Birmingham, said in Amgen’s news release.

lfranki@mdedge.com

The Food and Drug Administration has approved Prolia (denosumab) for the treatment of glucocorticoid-induced osteoporosis in adults at high risk of fracture, the drug’s manufacturer Amgen announced May 21.

FDA approval was based on 12-month primary analysis results from a randomized, double-blind, phase 3 trial. Patients who received a 60-mg dose of Prolia subcutaneously every 6 months had greater lumbar spine bone mineral density at 1 year than did those who received a 5-mg dose of risedronate daily in all study subpopulations. These results were maintained after researchers controlled for gender, race, geographic region, and menopausal status, as well as baseline age, lumbar spine bone mineral density T score, and glucocorticoid dose within each subpopulation.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The most common adverse events associated with Prolia during the phase 3 study were back pain, hypertension, bronchitis, and headache, which are in line with previously reported safety data.

“Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in bone mineral density within a few months of beginning treatment. With this approval, patients who receive treatment with glucocorticoids now have a new option to help improve their bone mineral density,” lead study author Kenneth F. Saag, MD, professor of medicine at the University of Alabama, Birmingham, said in Amgen’s news release.

lfranki@mdedge.com

The Food and Drug Administration has approved Prolia (denosumab) for the treatment of glucocorticoid-induced osteoporosis in adults at high risk of fracture, the drug’s manufacturer Amgen announced May 21.

FDA approval was based on 12-month primary analysis results from a randomized, double-blind, phase 3 trial. Patients who received a 60-mg dose of Prolia subcutaneously every 6 months had greater lumbar spine bone mineral density at 1 year than did those who received a 5-mg dose of risedronate daily in all study subpopulations. These results were maintained after researchers controlled for gender, race, geographic region, and menopausal status, as well as baseline age, lumbar spine bone mineral density T score, and glucocorticoid dose within each subpopulation.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The most common adverse events associated with Prolia during the phase 3 study were back pain, hypertension, bronchitis, and headache, which are in line with previously reported safety data.

“Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in bone mineral density within a few months of beginning treatment. With this approval, patients who receive treatment with glucocorticoids now have a new option to help improve their bone mineral density,” lead study author Kenneth F. Saag, MD, professor of medicine at the University of Alabama, Birmingham, said in Amgen’s news release.

lfranki@mdedge.com

Roseomonas mucosa bacteria obtained from healthy volunteers without atopic dermatitis reduced the severity of the disorder in a small, early-phase study of 10 adults and 5 children with atopic dermatitis. Also today, a new device could detect osteoarthritis with sound and motion, seven days of antibiotics is enough for gram-negative bacteremias, and canagliflozen is linked to lower HbA1c levels in younger patients.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Roseomonas mucosa bacteria obtained from healthy volunteers without atopic dermatitis reduced the severity of the disorder in a small, early-phase study of 10 adults and 5 children with atopic dermatitis. Also today, a new device could detect osteoarthritis with sound and motion, seven days of antibiotics is enough for gram-negative bacteremias, and canagliflozen is linked to lower HbA1c levels in younger patients.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Roseomonas mucosa bacteria obtained from healthy volunteers without atopic dermatitis reduced the severity of the disorder in a small, early-phase study of 10 adults and 5 children with atopic dermatitis. Also today, a new device could detect osteoarthritis with sound and motion, seven days of antibiotics is enough for gram-negative bacteremias, and canagliflozen is linked to lower HbA1c levels in younger patients.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

The Association of VA Hematology/Oncology (AVAHO) is now accepting abstracts for its annual meeting, September 28-30, 2018 in Chicago, Illinois. Authors must submit abstracts electronically through the AVAHO website and adhere to the following stipulations:

• The abstract should not exceed 350 words, excluding the title;
• The title cannot exceed 20 words;
• At least 1 author must be  a member of AVAHO;
• The copy should not include illustrations or bullet points; and
• All names of the contributing authors and their affiliated institutions must be provided.

All abstracts must be submitted by June 29, 2018. Accepted abstracts will be published by Federal Practitioner and mailed to AVAHO members. The abstracts also will be available at the conference for attendees. Click here for the 2016 and 2017 Abstracts.

More information on the submission process and abstract submission form can be found here. 

The Association of VA Hematology/Oncology (AVAHO) is now accepting abstracts for its annual meeting, September 28-30, 2018 in Chicago, Illinois. Authors must submit abstracts electronically through the AVAHO website and adhere to the following stipulations:

• The abstract should not exceed 350 words, excluding the title;
• The title cannot exceed 20 words;
• At least 1 author must be  a member of AVAHO;
• The copy should not include illustrations or bullet points; and
• All names of the contributing authors and their affiliated institutions must be provided.

All abstracts must be submitted by June 29, 2018. Accepted abstracts will be published by Federal Practitioner and mailed to AVAHO members. The abstracts also will be available at the conference for attendees. Click here for the 2016 and 2017 Abstracts.

More information on the submission process and abstract submission form can be found here. 

The Association of VA Hematology/Oncology (AVAHO) is now accepting abstracts for its annual meeting, September 28-30, 2018 in Chicago, Illinois. Authors must submit abstracts electronically through the AVAHO website and adhere to the following stipulations:

• The abstract should not exceed 350 words, excluding the title;
• The title cannot exceed 20 words;
• At least 1 author must be  a member of AVAHO;
• The copy should not include illustrations or bullet points; and
• All names of the contributing authors and their affiliated institutions must be provided.

All abstracts must be submitted by June 29, 2018. Accepted abstracts will be published by Federal Practitioner and mailed to AVAHO members. The abstracts also will be available at the conference for attendees. Click here for the 2016 and 2017 Abstracts.

More information on the submission process and abstract submission form can be found here. 

The US goal is to get Tuberculosis (TB) rates down to > 1 case per 1 million people, but in 2017 there were 28 cases per million. After years of decline, TB rates have stagnated among people born in the US. The TB rate dropped slightly (–2.5%) from 2016 to 2017. Another even slighter decrease was seen in 2017 (–1.8%). Moreover, < 1 in 10 TB cases occurred among children aged < 15 years (a “key marker” of recent transmission, the CDC says). Half of all cases were reported in California, New York, Texas, and Florida, all 4 corners of the country.

As many as 13 million people in the US have latent TB infection but the vast majority do not know it. On average, 5% - 10% of people with latent TB infection progress to infectious TB. More than 80% of US TB cases are associated with long-standing, untreated latent TB infections.

The CDC says reaching the elimination goal will take an “intensified, dual approach” that strengthens existing systems to prevent transmission of infectious TB disease and increases efforts to detect and treat latent infection before it progresses to infectious TB.

It is essential to ensure that every active case of TB disease is effectively detected and treated, the CDC says. Treatments can be difficult to complete; however, not completing treatment can lead to drug-resistant bacteria, and even lengthier and more expensive treatment. CDC research has identified a shorter regimen for people with latent infection: 12 once-weekly doses of isoniazid and rifapentine, a simpler treatment compared with other regimens that include a 270-dose,  and 9-month daily regimen of isoniazid.

Over the past 20 years, health departments and CDC TB control efforts have prevented an estimated 300,000 cases of TB disease. “Challenges remain,” says Philip LoBue, MD, director of CDC’s Division of Tuberculosis Elimination. But “[t]he good news is that the path to accelerated progress is clear.” In addition to the shorter treatment regimen, recent advances include electronic directly observed therapy (eDOT), which makes TB treatment less expensive and more convenient; and a diagnostic blood test that can provide accurate results in a single medical visit.

The US goal is to get Tuberculosis (TB) rates down to > 1 case per 1 million people, but in 2017 there were 28 cases per million. After years of decline, TB rates have stagnated among people born in the US. The TB rate dropped slightly (–2.5%) from 2016 to 2017. Another even slighter decrease was seen in 2017 (–1.8%). Moreover, < 1 in 10 TB cases occurred among children aged < 15 years (a “key marker” of recent transmission, the CDC says). Half of all cases were reported in California, New York, Texas, and Florida, all 4 corners of the country.

As many as 13 million people in the US have latent TB infection but the vast majority do not know it. On average, 5% - 10% of people with latent TB infection progress to infectious TB. More than 80% of US TB cases are associated with long-standing, untreated latent TB infections.

The CDC says reaching the elimination goal will take an “intensified, dual approach” that strengthens existing systems to prevent transmission of infectious TB disease and increases efforts to detect and treat latent infection before it progresses to infectious TB.

It is essential to ensure that every active case of TB disease is effectively detected and treated, the CDC says. Treatments can be difficult to complete; however, not completing treatment can lead to drug-resistant bacteria, and even lengthier and more expensive treatment. CDC research has identified a shorter regimen for people with latent infection: 12 once-weekly doses of isoniazid and rifapentine, a simpler treatment compared with other regimens that include a 270-dose,  and 9-month daily regimen of isoniazid.

Over the past 20 years, health departments and CDC TB control efforts have prevented an estimated 300,000 cases of TB disease. “Challenges remain,” says Philip LoBue, MD, director of CDC’s Division of Tuberculosis Elimination. But “[t]he good news is that the path to accelerated progress is clear.” In addition to the shorter treatment regimen, recent advances include electronic directly observed therapy (eDOT), which makes TB treatment less expensive and more convenient; and a diagnostic blood test that can provide accurate results in a single medical visit.

The US goal is to get Tuberculosis (TB) rates down to > 1 case per 1 million people, but in 2017 there were 28 cases per million. After years of decline, TB rates have stagnated among people born in the US. The TB rate dropped slightly (–2.5%) from 2016 to 2017. Another even slighter decrease was seen in 2017 (–1.8%). Moreover, < 1 in 10 TB cases occurred among children aged < 15 years (a “key marker” of recent transmission, the CDC says). Half of all cases were reported in California, New York, Texas, and Florida, all 4 corners of the country.

As many as 13 million people in the US have latent TB infection but the vast majority do not know it. On average, 5% - 10% of people with latent TB infection progress to infectious TB. More than 80% of US TB cases are associated with long-standing, untreated latent TB infections.

The CDC says reaching the elimination goal will take an “intensified, dual approach” that strengthens existing systems to prevent transmission of infectious TB disease and increases efforts to detect and treat latent infection before it progresses to infectious TB.

It is essential to ensure that every active case of TB disease is effectively detected and treated, the CDC says. Treatments can be difficult to complete; however, not completing treatment can lead to drug-resistant bacteria, and even lengthier and more expensive treatment. CDC research has identified a shorter regimen for people with latent infection: 12 once-weekly doses of isoniazid and rifapentine, a simpler treatment compared with other regimens that include a 270-dose,  and 9-month daily regimen of isoniazid.

Over the past 20 years, health departments and CDC TB control efforts have prevented an estimated 300,000 cases of TB disease. “Challenges remain,” says Philip LoBue, MD, director of CDC’s Division of Tuberculosis Elimination. But “[t]he good news is that the path to accelerated progress is clear.” In addition to the shorter treatment regimen, recent advances include electronic directly observed therapy (eDOT), which makes TB treatment less expensive and more convenient; and a diagnostic blood test that can provide accurate results in a single medical visit.

Image by Spencer Phillips

GLASGOW—New research suggests the gene therapy SPK-9001 can reduce bleeding and the need for factor IX infusions in patients with hemophilia B.

In an ongoing, phase 1/2 trial, SPK-9001 reduced the annualized bleeding rate (ABR) by 98% and the annualized infusion rate (AIR) by 99%.

All 15 patients treated with SPK-9001 have discontinued factor IX prophylaxis.

There have been no serious adverse events (AEs), no thrombotic events, and no factor IX inhibitors observed to date.

Spencer K. Sullivan, MD, of the Mississippi Center for Advanced Medicine in Madison, Mississippi, presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the “Free Papers: Gene Therapy” session on Tuesday.

The research was sponsored by Spark Therapeutics, the company developing SPK-9001 in collaboration with Pfizer.

SPK-9001 is an investigational vector that contains a bio-engineered adeno-associated virus capsid and a codon-optimized, high-activity human factor IX gene enabling endogenous production of factor IX.

Dr Sullivan reported results with SPK-9001 in 15 patients with severe or moderately severe hemophilia B.

As of the May 7, 2018, data cutoff, there were 13 patients with at least 12 weeks of follow-up after SPK-9001 infusion, which is the length of time required to achieve steady-state factor IX activity levels. All 13 patients reached stable factor IX levels of more than 12%.

The range of steady-state factor IX activity level, beginning at 12 weeks through 52 weeks of follow-up for the first 10 patients infused, was 14.3% to 76.8%.

The next 3 patients were infused with SPK-9001 manufactured using an enhanced process and reached 12 or more weeks of follow-up. For these patients, the range of steady-state factor IX activity level was 38.1% to 54.5%.

The 2 remaining patients had only 5 weeks and 11 weeks of follow-up as of the cut-off date.

Based on individual participant history for the year prior to the study, the overall ABR for all 15 patients was reduced by 98% four weeks after SPK-9001 treatment.

The ABR was 0.2 bleeds per patient after SPK-9001, compared to an ABR of 8.9 before SPK-9001.

One patient experienced a bleeding event 4 or more weeks after SPK-9001 infusion.

The overall AIR was reduced by 99% (based on data after week 4) for all 15 patients. The AIR was 0.9 infusions per patient after SPK-9001, compared to 57.2 infusions before SPK-9001.

Six patients received factor IX infusions following SPK-9001 administration—2 for reported spontaneous bleeds, 2 prior to surgery, 1 at the end of the study (discretionary, per protocol), and 1 for prophylaxis for a minor, traumatic non-bleeding event.

However, all 15 patients have discontinued regular factor IX prophylaxis.

There have been no serious AEs or factor IX inhibitors reported.

Two patients (1 who received SPK-9001 manufactured using the enhanced process) experienced related AEs of elevated transaminases, which were asymptomatic.

These patients were treated with a tapering course of oral corticosteroids, and 1 event resolved before the data cutoff.

An additional patient received a tapering course of oral corticosteroids for an increase in liver enzymes (not exceeding the upper limit of normal) temporally associated with falling levels of factor IX activity.

“We are pleased to see all 15 participants, notably including the first 4 participants who have been followed for more than 2 years, continue to show that a single administration of SPK-9001 has resulted in dramatic reductions in bleeding and factor IX infusions, with no serious adverse events,” said Katherine A. High, MD, president and head of research & development at Spark Therapeutics.

“Our commitment to gene therapy research across our hemophilia programs remains steadfast with the goal of developing a novel therapeutic approach with a positive benefit-risk profile that aims to free patients of the need for regular infusions, while eliminating spontaneous bleeding.”

Image by Spencer Phillips

GLASGOW—New research suggests the gene therapy SPK-9001 can reduce bleeding and the need for factor IX infusions in patients with hemophilia B.

In an ongoing, phase 1/2 trial, SPK-9001 reduced the annualized bleeding rate (ABR) by 98% and the annualized infusion rate (AIR) by 99%.

All 15 patients treated with SPK-9001 have discontinued factor IX prophylaxis.

There have been no serious adverse events (AEs), no thrombotic events, and no factor IX inhibitors observed to date.

Spencer K. Sullivan, MD, of the Mississippi Center for Advanced Medicine in Madison, Mississippi, presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the “Free Papers: Gene Therapy” session on Tuesday.

The research was sponsored by Spark Therapeutics, the company developing SPK-9001 in collaboration with Pfizer.

SPK-9001 is an investigational vector that contains a bio-engineered adeno-associated virus capsid and a codon-optimized, high-activity human factor IX gene enabling endogenous production of factor IX.

Dr Sullivan reported results with SPK-9001 in 15 patients with severe or moderately severe hemophilia B.

As of the May 7, 2018, data cutoff, there were 13 patients with at least 12 weeks of follow-up after SPK-9001 infusion, which is the length of time required to achieve steady-state factor IX activity levels. All 13 patients reached stable factor IX levels of more than 12%.

The range of steady-state factor IX activity level, beginning at 12 weeks through 52 weeks of follow-up for the first 10 patients infused, was 14.3% to 76.8%.

The next 3 patients were infused with SPK-9001 manufactured using an enhanced process and reached 12 or more weeks of follow-up. For these patients, the range of steady-state factor IX activity level was 38.1% to 54.5%.

The 2 remaining patients had only 5 weeks and 11 weeks of follow-up as of the cut-off date.

Based on individual participant history for the year prior to the study, the overall ABR for all 15 patients was reduced by 98% four weeks after SPK-9001 treatment.

The ABR was 0.2 bleeds per patient after SPK-9001, compared to an ABR of 8.9 before SPK-9001.

One patient experienced a bleeding event 4 or more weeks after SPK-9001 infusion.

The overall AIR was reduced by 99% (based on data after week 4) for all 15 patients. The AIR was 0.9 infusions per patient after SPK-9001, compared to 57.2 infusions before SPK-9001.

Six patients received factor IX infusions following SPK-9001 administration—2 for reported spontaneous bleeds, 2 prior to surgery, 1 at the end of the study (discretionary, per protocol), and 1 for prophylaxis for a minor, traumatic non-bleeding event.

However, all 15 patients have discontinued regular factor IX prophylaxis.

There have been no serious AEs or factor IX inhibitors reported.

Two patients (1 who received SPK-9001 manufactured using the enhanced process) experienced related AEs of elevated transaminases, which were asymptomatic.

These patients were treated with a tapering course of oral corticosteroids, and 1 event resolved before the data cutoff.

An additional patient received a tapering course of oral corticosteroids for an increase in liver enzymes (not exceeding the upper limit of normal) temporally associated with falling levels of factor IX activity.

“We are pleased to see all 15 participants, notably including the first 4 participants who have been followed for more than 2 years, continue to show that a single administration of SPK-9001 has resulted in dramatic reductions in bleeding and factor IX infusions, with no serious adverse events,” said Katherine A. High, MD, president and head of research & development at Spark Therapeutics.

“Our commitment to gene therapy research across our hemophilia programs remains steadfast with the goal of developing a novel therapeutic approach with a positive benefit-risk profile that aims to free patients of the need for regular infusions, while eliminating spontaneous bleeding.”

Image by Spencer Phillips

GLASGOW—New research suggests the gene therapy SPK-9001 can reduce bleeding and the need for factor IX infusions in patients with hemophilia B.

In an ongoing, phase 1/2 trial, SPK-9001 reduced the annualized bleeding rate (ABR) by 98% and the annualized infusion rate (AIR) by 99%.

All 15 patients treated with SPK-9001 have discontinued factor IX prophylaxis.

There have been no serious adverse events (AEs), no thrombotic events, and no factor IX inhibitors observed to date.

Spencer K. Sullivan, MD, of the Mississippi Center for Advanced Medicine in Madison, Mississippi, presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the “Free Papers: Gene Therapy” session on Tuesday.

The research was sponsored by Spark Therapeutics, the company developing SPK-9001 in collaboration with Pfizer.

SPK-9001 is an investigational vector that contains a bio-engineered adeno-associated virus capsid and a codon-optimized, high-activity human factor IX gene enabling endogenous production of factor IX.

Dr Sullivan reported results with SPK-9001 in 15 patients with severe or moderately severe hemophilia B.

As of the May 7, 2018, data cutoff, there were 13 patients with at least 12 weeks of follow-up after SPK-9001 infusion, which is the length of time required to achieve steady-state factor IX activity levels. All 13 patients reached stable factor IX levels of more than 12%.

The range of steady-state factor IX activity level, beginning at 12 weeks through 52 weeks of follow-up for the first 10 patients infused, was 14.3% to 76.8%.

The next 3 patients were infused with SPK-9001 manufactured using an enhanced process and reached 12 or more weeks of follow-up. For these patients, the range of steady-state factor IX activity level was 38.1% to 54.5%.

The 2 remaining patients had only 5 weeks and 11 weeks of follow-up as of the cut-off date.

Based on individual participant history for the year prior to the study, the overall ABR for all 15 patients was reduced by 98% four weeks after SPK-9001 treatment.

The ABR was 0.2 bleeds per patient after SPK-9001, compared to an ABR of 8.9 before SPK-9001.

One patient experienced a bleeding event 4 or more weeks after SPK-9001 infusion.

The overall AIR was reduced by 99% (based on data after week 4) for all 15 patients. The AIR was 0.9 infusions per patient after SPK-9001, compared to 57.2 infusions before SPK-9001.

Six patients received factor IX infusions following SPK-9001 administration—2 for reported spontaneous bleeds, 2 prior to surgery, 1 at the end of the study (discretionary, per protocol), and 1 for prophylaxis for a minor, traumatic non-bleeding event.

However, all 15 patients have discontinued regular factor IX prophylaxis.

There have been no serious AEs or factor IX inhibitors reported.

Two patients (1 who received SPK-9001 manufactured using the enhanced process) experienced related AEs of elevated transaminases, which were asymptomatic.

These patients were treated with a tapering course of oral corticosteroids, and 1 event resolved before the data cutoff.

An additional patient received a tapering course of oral corticosteroids for an increase in liver enzymes (not exceeding the upper limit of normal) temporally associated with falling levels of factor IX activity.

“We are pleased to see all 15 participants, notably including the first 4 participants who have been followed for more than 2 years, continue to show that a single administration of SPK-9001 has resulted in dramatic reductions in bleeding and factor IX infusions, with no serious adverse events,” said Katherine A. High, MD, president and head of research & development at Spark Therapeutics.

“Our commitment to gene therapy research across our hemophilia programs remains steadfast with the goal of developing a novel therapeutic approach with a positive benefit-risk profile that aims to free patients of the need for regular infusions, while eliminating spontaneous bleeding.”

Photo from Novo Nordisk

GLASGOW—Nonacog beta pegol (N9-GP) has a better pharmacokinetic (PK) profile than recombinant factor IX-Fc fusion protein (rFIXFc), according to researchers.

In a phase 1 trial, adults with hemophilia B who received a single dose of N9-GP achieved greater total factor IX exposure than those treated with rFIXFc, and N9-GP had a longer half-life.

Seven days after injection, factor IX activity was 6-fold greater in patients treated with N9-GP than in those treated with rFIXFc at the same dose.

“As a clinician, I know first-hand how challenging it can be to help people living with hemophilia B reach their treatment goals and be adequately protected from bleeding,” said Carmen Escuriola Ettingshausen, MD, of Haemophilia Centre Rhein Main in Frankfurt-Mörfelden, Germany.

“These data will help us better understand the different treatment options and choose the appropriate treatment for each patient.”

Dr Ettingshausen presented the data at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday.

The research was sponsored by Novo Nordisk A/S, the company marketing N9-GP (as Rebinyn or Refixia). N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.

In the Paradigm7 trial, researchers compared the PK profiles of N9-GP and rFIXFc (Alprolix).

Fifteen previously treated adult males with congenital hemophilia B (factor IX activity ≤2%) received single injections (50 IU/kg) of N9-GP and rFIXFc with at least 21 days between doses.

One patient was excluded from the analysis due to intake of a prohibited medication (an rFIXFc product that was not Alprolix). Two other patients were excluded from some analyses because they missed 2 PK time points.

The primary endpoint was dose-normalized area under the factor IX activity-time curve from 0 to infinity (AUC_0-inf,norm).

The estimated AUC_0-inf,norm (n=12) was significantly higher for N9-GP than rFIXFc—9656 IU*h/dL and 2199 IU*h/dL, respectively (ratio=4.39, P<0.0001).

There were significant differences for secondary endpoints as well.

The maximum factor IX activity dose-normalized to 50 IU/kg (n=14) was 91 IU/dL with N9-GP and 45 IU/dL with rFIXFc (ratio=2.02, P<0.001).

The incremental recovery at 30 minutes (n=14) was 1.7 (IU/dL)/(IU/kg) with N9-GP and 0.8 (IU/dL)/(IU/kg) with rFIXFc (ratio=2.20, P<0.001).

The terminal half-life (n=12) was 103.2 hours with N9-GP and 84.9 hours with rFIXFc (ratio=1.22, P<0.001).

The clearance (n=12) was 0.52 mL/h/kg with N9-GP and 2.25 mL/h/kg with rFIXFc (ratio=0.23, P<0.001).

The factor IX activity at 168 hours (n=12) was 19 IU/dL with N9-GP and 3 IU/dL with rFIXFc (ratio=5.80, P<0.001).

None of the patients developed inhibitors, and no safety concerns were identified, according to Novo Nordisk. The company did not provide additional safety information.

Photo from Novo Nordisk

GLASGOW—Nonacog beta pegol (N9-GP) has a better pharmacokinetic (PK) profile than recombinant factor IX-Fc fusion protein (rFIXFc), according to researchers.

In a phase 1 trial, adults with hemophilia B who received a single dose of N9-GP achieved greater total factor IX exposure than those treated with rFIXFc, and N9-GP had a longer half-life.

Seven days after injection, factor IX activity was 6-fold greater in patients treated with N9-GP than in those treated with rFIXFc at the same dose.

“As a clinician, I know first-hand how challenging it can be to help people living with hemophilia B reach their treatment goals and be adequately protected from bleeding,” said Carmen Escuriola Ettingshausen, MD, of Haemophilia Centre Rhein Main in Frankfurt-Mörfelden, Germany.

“These data will help us better understand the different treatment options and choose the appropriate treatment for each patient.”

Dr Ettingshausen presented the data at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday.

The research was sponsored by Novo Nordisk A/S, the company marketing N9-GP (as Rebinyn or Refixia). N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.

In the Paradigm7 trial, researchers compared the PK profiles of N9-GP and rFIXFc (Alprolix).

Fifteen previously treated adult males with congenital hemophilia B (factor IX activity ≤2%) received single injections (50 IU/kg) of N9-GP and rFIXFc with at least 21 days between doses.

One patient was excluded from the analysis due to intake of a prohibited medication (an rFIXFc product that was not Alprolix). Two other patients were excluded from some analyses because they missed 2 PK time points.

The primary endpoint was dose-normalized area under the factor IX activity-time curve from 0 to infinity (AUC_0-inf,norm).

The estimated AUC_0-inf,norm (n=12) was significantly higher for N9-GP than rFIXFc—9656 IU*h/dL and 2199 IU*h/dL, respectively (ratio=4.39, P<0.0001).

There were significant differences for secondary endpoints as well.

The maximum factor IX activity dose-normalized to 50 IU/kg (n=14) was 91 IU/dL with N9-GP and 45 IU/dL with rFIXFc (ratio=2.02, P<0.001).

The incremental recovery at 30 minutes (n=14) was 1.7 (IU/dL)/(IU/kg) with N9-GP and 0.8 (IU/dL)/(IU/kg) with rFIXFc (ratio=2.20, P<0.001).

The terminal half-life (n=12) was 103.2 hours with N9-GP and 84.9 hours with rFIXFc (ratio=1.22, P<0.001).

The clearance (n=12) was 0.52 mL/h/kg with N9-GP and 2.25 mL/h/kg with rFIXFc (ratio=0.23, P<0.001).

The factor IX activity at 168 hours (n=12) was 19 IU/dL with N9-GP and 3 IU/dL with rFIXFc (ratio=5.80, P<0.001).

None of the patients developed inhibitors, and no safety concerns were identified, according to Novo Nordisk. The company did not provide additional safety information.

Photo from Novo Nordisk

GLASGOW—Nonacog beta pegol (N9-GP) has a better pharmacokinetic (PK) profile than recombinant factor IX-Fc fusion protein (rFIXFc), according to researchers.

In a phase 1 trial, adults with hemophilia B who received a single dose of N9-GP achieved greater total factor IX exposure than those treated with rFIXFc, and N9-GP had a longer half-life.

Seven days after injection, factor IX activity was 6-fold greater in patients treated with N9-GP than in those treated with rFIXFc at the same dose.

“As a clinician, I know first-hand how challenging it can be to help people living with hemophilia B reach their treatment goals and be adequately protected from bleeding,” said Carmen Escuriola Ettingshausen, MD, of Haemophilia Centre Rhein Main in Frankfurt-Mörfelden, Germany.

“These data will help us better understand the different treatment options and choose the appropriate treatment for each patient.”

Dr Ettingshausen presented the data at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday.

The research was sponsored by Novo Nordisk A/S, the company marketing N9-GP (as Rebinyn or Refixia). N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.

In the Paradigm7 trial, researchers compared the PK profiles of N9-GP and rFIXFc (Alprolix).

Fifteen previously treated adult males with congenital hemophilia B (factor IX activity ≤2%) received single injections (50 IU/kg) of N9-GP and rFIXFc with at least 21 days between doses.

One patient was excluded from the analysis due to intake of a prohibited medication (an rFIXFc product that was not Alprolix). Two other patients were excluded from some analyses because they missed 2 PK time points.

The primary endpoint was dose-normalized area under the factor IX activity-time curve from 0 to infinity (AUC_0-inf,norm).

The estimated AUC_0-inf,norm (n=12) was significantly higher for N9-GP than rFIXFc—9656 IU*h/dL and 2199 IU*h/dL, respectively (ratio=4.39, P<0.0001).

There were significant differences for secondary endpoints as well.

The maximum factor IX activity dose-normalized to 50 IU/kg (n=14) was 91 IU/dL with N9-GP and 45 IU/dL with rFIXFc (ratio=2.02, P<0.001).

The incremental recovery at 30 minutes (n=14) was 1.7 (IU/dL)/(IU/kg) with N9-GP and 0.8 (IU/dL)/(IU/kg) with rFIXFc (ratio=2.20, P<0.001).

The terminal half-life (n=12) was 103.2 hours with N9-GP and 84.9 hours with rFIXFc (ratio=1.22, P<0.001).

The clearance (n=12) was 0.52 mL/h/kg with N9-GP and 2.25 mL/h/kg with rFIXFc (ratio=0.23, P<0.001).

The factor IX activity at 168 hours (n=12) was 19 IU/dL with N9-GP and 3 IU/dL with rFIXFc (ratio=5.80, P<0.001).

None of the patients developed inhibitors, and no safety concerns were identified, according to Novo Nordisk. The company did not provide additional safety information.

Antihemophilic factor

GLASGOW—Preliminary data suggest an investigational therapy can extend the half-life of factor VIII (FVIII) in patients with severe hemophilia A.

Researchers are testing the therapy, BIVV001, in a phase 1/2a trial and have reported results in 4 patients.

BIVV001 extended the half-life of FVIII to 37 hours, with an average FVIII activity of 5.6% at 7 days post-infusion.

“For decades, scientists have been trying to overcome the von Willebrand factor ceiling, which imposes a limit on the half-life of FVIII, and these data demonstrate that BIVV001 has finally broken through that ceiling,” said Joachim Fruebis, PhD, senior vice president of development at Bioverativ Inc.

Dr Fruebis presented these data at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday.

The research was sponsored by Bioverativ, the company developing BIVV001.

BIVV001 (rFVIIIFc-VWF-XTEN) is a recombinant FVIII therapy that builds on Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to potentially extend its time in circulation.

In the phase 1/2a EXTEN-A trial, researchers are evaluating the safety and pharmacokinetics of BIVV001 in a low-dose and high-dose cohort of subjects, ages 18 to 65, who have severe hemophilia A.

In the data presented at the WFH World Congress, 4 adult males received a single dose of recombinant FVIII therapy (25 IU/kg) followed, after a washout period, by a single, low dose of BIVV001 (25 IU/kg).

Primary endpoints of this study include the occurrence of adverse events and the development of inhibitors.

No inhibitors have been detected, and BIBV001 was “generally well-tolerated,” according to Bioverativ. The company did not provide additional safety information.

BIVV001 extended the half-life of FVIII to 37 hours, which is an increase over the 13 hours seen with recombinant FVIII.

The average FVIII activity for the 4 subjects was 13.0% at 5 days and 5.6% at 7 days post-infusion.

“Importantly for the hemophilia community, the factor levels seen in this study are unparalleled in hemophilia A,” Dr Fruebis said, “and we are excited about the potential for BIVV001 to transform the treatment paradigm for patients and physicians.”

Antihemophilic factor

GLASGOW—Preliminary data suggest an investigational therapy can extend the half-life of factor VIII (FVIII) in patients with severe hemophilia A.

Researchers are testing the therapy, BIVV001, in a phase 1/2a trial and have reported results in 4 patients.

BIVV001 extended the half-life of FVIII to 37 hours, with an average FVIII activity of 5.6% at 7 days post-infusion.

“For decades, scientists have been trying to overcome the von Willebrand factor ceiling, which imposes a limit on the half-life of FVIII, and these data demonstrate that BIVV001 has finally broken through that ceiling,” said Joachim Fruebis, PhD, senior vice president of development at Bioverativ Inc.

Dr Fruebis presented these data at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday.

The research was sponsored by Bioverativ, the company developing BIVV001.

BIVV001 (rFVIIIFc-VWF-XTEN) is a recombinant FVIII therapy that builds on Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to potentially extend its time in circulation.

In the phase 1/2a EXTEN-A trial, researchers are evaluating the safety and pharmacokinetics of BIVV001 in a low-dose and high-dose cohort of subjects, ages 18 to 65, who have severe hemophilia A.

In the data presented at the WFH World Congress, 4 adult males received a single dose of recombinant FVIII therapy (25 IU/kg) followed, after a washout period, by a single, low dose of BIVV001 (25 IU/kg).

Primary endpoints of this study include the occurrence of adverse events and the development of inhibitors.

No inhibitors have been detected, and BIBV001 was “generally well-tolerated,” according to Bioverativ. The company did not provide additional safety information.

BIVV001 extended the half-life of FVIII to 37 hours, which is an increase over the 13 hours seen with recombinant FVIII.

The average FVIII activity for the 4 subjects was 13.0% at 5 days and 5.6% at 7 days post-infusion.

“Importantly for the hemophilia community, the factor levels seen in this study are unparalleled in hemophilia A,” Dr Fruebis said, “and we are excited about the potential for BIVV001 to transform the treatment paradigm for patients and physicians.”

Antihemophilic factor

GLASGOW—Preliminary data suggest an investigational therapy can extend the half-life of factor VIII (FVIII) in patients with severe hemophilia A.

Researchers are testing the therapy, BIVV001, in a phase 1/2a trial and have reported results in 4 patients.

BIVV001 extended the half-life of FVIII to 37 hours, with an average FVIII activity of 5.6% at 7 days post-infusion.

“For decades, scientists have been trying to overcome the von Willebrand factor ceiling, which imposes a limit on the half-life of FVIII, and these data demonstrate that BIVV001 has finally broken through that ceiling,” said Joachim Fruebis, PhD, senior vice president of development at Bioverativ Inc.

Dr Fruebis presented these data at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday.

The research was sponsored by Bioverativ, the company developing BIVV001.

BIVV001 (rFVIIIFc-VWF-XTEN) is a recombinant FVIII therapy that builds on Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to potentially extend its time in circulation.

In the phase 1/2a EXTEN-A trial, researchers are evaluating the safety and pharmacokinetics of BIVV001 in a low-dose and high-dose cohort of subjects, ages 18 to 65, who have severe hemophilia A.

In the data presented at the WFH World Congress, 4 adult males received a single dose of recombinant FVIII therapy (25 IU/kg) followed, after a washout period, by a single, low dose of BIVV001 (25 IU/kg).

Primary endpoints of this study include the occurrence of adverse events and the development of inhibitors.

No inhibitors have been detected, and BIBV001 was “generally well-tolerated,” according to Bioverativ. The company did not provide additional safety information.

BIVV001 extended the half-life of FVIII to 37 hours, which is an increase over the 13 hours seen with recombinant FVIII.

The average FVIII activity for the 4 subjects was 13.0% at 5 days and 5.6% at 7 days post-infusion.

“Importantly for the hemophilia community, the factor levels seen in this study are unparalleled in hemophilia A,” Dr Fruebis said, “and we are excited about the potential for BIVV001 to transform the treatment paradigm for patients and physicians.”