Patients treated with golimumab Mean duration of follow-up (weeks) Mean exposure (number of administrations) Patients with one or more adverse events Patients with one or more serious adverse events Patients who discontinued study agent due to an adverse event Patients with one or more infections Patients with one or more serious infections Patients with one or more injection-site reactions to golimumab Injections with one or more injection-site reactions to golimumab Patients with one or more malignancies Patients with markedly abnormal**: Alanine aminotransferase Aspartate aminotransferase Total bilirubin Patients negative for antinuclear antibodies at baseline Patients positive for antinuclear antibodies at week 104 Patients positive for anti-double-stranded DNA at week 104 41 79.0 19.1 36 (87.8) 4 (9.8) 1 (2.4) 28 (68.3) 2 (4.9) 3 (7.3) 1 (2.4) 1 (2.4) 1 (2.4) 0 (0.0) 31 1 (3.2) 1 (100) 34 77.6 18.6 29 (85.3) 2 (5.9) 0 (0.0) 10 (29.4) 0 (0.0) 3 (8.8) 0 (0.0) 1 (2.9) 0 (0.0) 1 (2.9) 27 3 (11.1) 0 (0.0) 138 79.2 19.2 130 (94.2) 10 (7.2) 6 (4.3) 90 (65.2) 1 (0.7) 11 (8.0) 0 (0.0) 1 (0.7) 0 (0.0) 4 (2.9) 80 2 (2.5) 0 (0.0) 25 72.0 17.1 23 (92.0) 3 (12.0) 2 (8.0) 17 (68.0) 1 (4.0) 6 (24.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 14 1 (7.1) 0 (0.0) Clinical and epidemiological research Table 2 Summary of adverse events through week 104* Placebo → golimumab 50 mg (group 1) Early escape Crossover (week 16–104)† (week 24–104)‡ Golimumab 50 mg (group 2) 50 mg only§ Golimumab 100 mg (group 3) Early escape (50 mg →100 mg)† 100 mg¶ 140 95.9 23.0 135 (96.4) 21 (15.0) 10 (7.1) 101 (72.1) 6 (4.3) 16 (11.4) 1 (0.7) 7 (5.0) 4 (2.9) 3 (2.1) 90 5 (5.6) 0 (0.0) All golimumab 353 90.7 21.8 332 (94.1) 40 (11.3) 19 (5.4) 241 (68.3) 11 (3.1) 38 (10.8) 2 (0.6) 10 (2.8) 5 (1.4) 8 (2.3) 232 11 (4.7) 1 (9.1) 3/784 (0.4) 19/634 (3.0) 16/2640 (0.6) 29/427 (6.8) 39/3220 (1.2) 106/7705 (1.4) Data presented as n (%) unless otherwise noted. *Patients are counted in the dosing group in which they were assigned at the time of the event. †Patients in these groups met the early escape criteria at week 16. ‡Patients in this group did not discontinue study agent prior to week 24 and crossed over at week 24. §This group included patients randomised to golimumab 50 mg irrespective of early escape status. Adverse events for patients who met early escape are only counted up to week 16. ¶This group included all patients randomised to golimumab 100 mg. **Predeﬁned as postbaseline values of ≥2 times the baseline value and >150 IU/mL (alanine/aspartate aminotransferase) or ≥2 times the baseline value and >1.5 mg/dl (total bilirubin). or improved through week 104. This was demonstrated even by the conservative analysis in which patients who met vari- ous treatment failure criteria, including early escape, were con- sidered to be non-responders throughout the remainder of the study. Improvement was generally similar between the two golimumab doses for the end points assessed. In addition to the original treatment assignments, the study protocol included treatment adjustments at week 16 based on patients’ improvement in the total back pain score and morning stiffness (ie, early escape) that included crossover from placebo to active treatment or dose escalation from 50 to 100 mg. The ﬁndings showed that among patients who received golimumab from the beginning of the study and who did not meet the early escape criteria, greater proportions achieved ASAS20, ASAS40 and BASDAI50 responses, and improvements in BASFI, BASMI, and PCS and MCS scores of the SF-36 (health-related quality of life) were greater than those in patients who required early crossover or dose escalation. Furthermore, an increase in goli- mumab dose from 50 to 100 mg in group 2 patients who entered early escape did not appear to substantially increase response rates in this subset of patients. Thus, given the consistency of these ﬁndings across parameters, patients who required early escape may have had more refractory disease. Another implica- tion of this ﬁnding is that patients with AS who do not improve by even 20% in total back pain score and morning stiffness after 16 weeks of treatment may have a reduced likelihood of responding to continued golimumab treatment. As expected, patients in group 1 who received placebo during the ﬁrst part of the study were more likely to require early escape 666 at week 16 than those in the other groups. Patients in this group who entered early escape at week 16 or subsequently crossed over to golimumab 50 mg at week 24 demonstrated patterns of response after receiving active treatment that were similar to those observed in patients initially randomised to golimumab. Of the few patients who required early escape in group 2 (goli- mumab 50 mg), almost half (44%) achieved an ASAS20 response at week 104. However, the beneﬁt of dose escalation from goli- mumab 50 mg to 100 mg cannot be fully elucidated from this study because there was no comparison with patients who met the criteria for early escape but remained on golimumab 50 mg. The proportion of patients in group 3 (golimumab 100 mg) who met the criteria for early escape at week 16 was similar to that of group 2, as were the ASAS20 response rates at week 104 for both early escape subgroups. Safety results through week 104 were similar to those through week 24 in that golimumab was generally well tolerated, and adverse event patterns were consistent with the known safety proﬁle of TNF inhibitors. The increased rate of serious infec- tions with the 100 mg dose of golimumab in this study is consis- tent with results of previous studies of TNF inhibitors in which patients receiving higher doses had a greater risk of serious infections compared with patients receiving lower doses.10 11 Although patients with active AS may derive additional beneﬁt from the 100 mg dose, the possibly increased risk of serious infec- tions compared with the 50 mg dose should be considered. This analysis was limited by the lack of a placebo compara- tor group after week 24; because of the placebo crossover, all patients received blinded, active treatment from week 24 to Ann Rheum Dis 2012;71:661–667. doi:10.1136/ard.2011.154799